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  • 301. Lu, Yingchang
    et al.
    Day, Felix R
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Buchkovich, Martin L
    Na, Jianbo
    Bataille, Veronique
    Cousminer, Diana L
    Dastani, Zari
    Drong, Alexander W
    Esko, Tõnu
    Evans, David M
    Falchi, Mario
    Feitosa, Mary F
    Ferreira, Teresa
    Hedman, Åsa K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Haring, Robin
    Hysi, Pirro G
    Iles, Mark M
    Justice, Anne E
    Kanoni, Stavroula
    Lagou, Vasiliki
    Li, Rui
    Li, Xin
    Locke, Adam
    Lu, Chen
    Mägi, Reedik
    Perry, John R B
    Pers, Tune H
    Qi, Qibin
    Sanna, Marianna
    Schmidt, Ellen M
    Scott, William R
    Shungin, Dmitry
    Teumer, Alexander
    Vinkhuyzen, Anna A E
    Walker, Ryan W
    Westra, Harm-Jan
    Zhang, Mingfeng
    Zhang, Weihua
    Zhao, Jing Hua
    Zhu, Zhihong
    Afzal, Uzma
    Ahluwalia, Tarunveer Singh
    Bakker, Stephan J L
    Bellis, Claire
    Bonnefond, Amélie
    Borodulin, Katja
    Buchman, Aron S
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Choh, Audrey C
    Choi, Hyung Jin
    Curran, Joanne E
    de Groot, Lisette C P G M
    De Jager, Philip L
    Dhonukshe-Rutten, Rosalie A M
    Enneman, Anke W
    Eury, Elodie
    Evans, Daniel S
    Forsen, Tom
    Friedrich, Nele
    Fumeron, Frédéric
    Garcia, Melissa E
    Gärtner, Simone
    Han, Bok-Ghee
    Havulinna, Aki S
    Hayward, Caroline
    Hernandez, Dena
    Hillege, Hans
    Ittermann, Till
    Kent, Jack W
    Kolcic, Ivana
    Laatikainen, Tiina
    Lahti, Jari
    Mateo Leach, Irene
    Lee, Christine G
    Lee, Jong-Young
    Liu, Tian
    Liu, Youfang
    Lobbens, Stéphane
    Loh, Marie
    Lyytikäinen, Leo-Pekka
    Medina-Gomez, Carolina
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nalls, Mike A
    Nielson, Carrie M
    Oozageer, Laticia
    Pascoe, Laura
    Paternoster, Lavinia
    Polašek, Ozren
    Ripatti, Samuli
    Sarzynski, Mark A
    Shin, Chan Soo
    Narančić, Nina Smolej
    Spira, Dominik
    Srikanth, Priya
    Steinhagen-Thiessen, Elisabeth
    Sung, Yun Ju
    Swart, Karin M A
    Taittonen, Leena
    Tanaka, Toshiko
    Tikkanen, Emmi
    van der Velde, Nathalie
    van Schoor, Natasja M
    Verweij, Niek
    Wright, Alan F
    Yu, Lei
    Zmuda, Joseph M
    Eklund, Niina
    Forrester, Terrence
    Grarup, Niels
    Jackson, Anne U
    Kristiansson, Kati
    Kuulasmaa, Teemu
    Kuusisto, Johanna
    Lichtner, Peter
    Luan, Jian'an
    Mahajan, Anubha
    Männistö, Satu
    Palmer, Cameron D
    Ried, Janina S
    Scott, Robert A
    Stancáková, Alena
    Wagner, Peter J
    Demirkan, Ayse
    Döring, Angela
    Gudnason, Vilmundur
    Kiel, Douglas P
    Kühnel, Brigitte
    Mangino, Massimo
    Mcknight, Barbara
    Menni, Cristina
    O'Connell, Jeffrey R
    Oostra, Ben A
    Shuldiner, Alan R
    Song, Kijoung
    Vandenput, Liesbeth
    van Duijn, Cornelia M
    Vollenweider, Peter
    White, Charles C
    Boehnke, Michael
    Boettcher, Yvonne
    Cooper, Richard S
    Forouhi, Nita G
    Gieger, Christian
    Grallert, Harald
    Hingorani, Aroon
    Jørgensen, Torben
    Jousilahti, Pekka
    Kivimaki, Mika
    Kumari, Meena
    Laakso, Markku
    Langenberg, Claudia
    Linneberg, Allan
    Luke, Amy
    Mckenzie, Colin A
    Palotie, Aarno
    Pedersen, Oluf
    Peters, Annette
    Strauch, Konstantin
    Tayo, Bamidele O
    Wareham, Nicholas J
    Bennett, David A
    Bertram, Lars
    Blangero, John
    Blüher, Matthias
    Bouchard, Claude
    Campbell, Harry
    Cho, Nam H
    Cummings, Steven R
    Czerwinski, Stefan A
    Demuth, Ilja
    Eckardt, Rahel
    Eriksson, Johan G
    Ferrucci, Luigi
    Franco, Oscar H
    Froguel, Philippe
    Gansevoort, Ron T
    Hansen, Torben
    Harris, Tamara B
    Hastie, Nicholas
    Heliövaara, Markku
    Hofman, Albert
    Jordan, Joanne M
    Jula, Antti
    Kähönen, Mika
    Kajantie, Eero
    Knekt, Paul B
    Koskinen, Seppo
    Kovacs, Peter
    Lehtimäki, Terho
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Liu, Yongmei
    Orwoll, Eric S
    Osmond, Clive
    Perola, Markus
    Pérusse, Louis
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rice, Treva K
    Rivadeneira, Fernando
    Rudan, Igor
    Salomaa, Veikko
    Sørensen, Thorkild I A
    Stumvoll, Michael
    Tönjes, Anke
    Towne, Bradford
    Tranah, Gregory J
    Tremblay, Angelo
    Uitterlinden, André G
    van der Harst, Pim
    Vartiainen, Erkki
    Viikari, Jorma S
    Vitart, Veronique
    Vohl, Marie-Claude
    Völzke, Henry
    Walker, Mark
    Wallaschofski, Henri
    Wild, Sarah
    Wilson, James F
    Yengo, Loïc
    Bishop, D Timothy
    Borecki, Ingrid B
    Chambers, John C
    Cupples, L Adrienne
    Dehghan, Abbas
    Deloukas, Panos
    Fatemifar, Ghazaleh
    Fox, Caroline
    Furey, Terrence S
    Franke, Lude
    Han, Jiali
    Hunter, David J
    Karjalainen, Juha
    Karpe, Fredrik
    Kaplan, Robert C
    Kooner, Jaspal S
    McCarthy, Mark I
    Murabito, Joanne M
    Morris, Andrew P
    Bishop, Julia A N
    North, Kari E
    Ohlsson, Claes
    Ong, Ken K
    Prokopenko, Inga
    Richards, J Brent
    Schadt, Eric E
    Spector, Tim D
    Widén, Elisabeth
    Willer, Cristen J
    Yang, Jian
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Mohlke, Karen L
    Hirschhorn, Joel N
    Pospisilik, John Andrew
    Zillikens, M Carola
    Lindgren, Cecilia
    Kilpeläinen, Tuomas Oskari
    Loos, Ruth J F
    New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk2016In: Nature Communications, E-ISSN 2041-1723, Vol. 7, article id 10495Article in journal (Refereed)
    Abstract [en]

    To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

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  • 302.
    Luis, Desiree
    et al.
    Karolinska Inst, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Huang, Xiaoyan
    Karolinska Inst, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Karolinska Inst, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carrero, Juan Jesus
    Karolinska Inst, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Dietary Acid Load, Kidney Function, Changes in Blood Pressure and Hypertension Incidence in Community Dwelling Elderly Men2015In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30Article in journal (Other academic)
  • 303.
    Lund, Lars H.
    et al.
    Karolinska Institute, Department of Medicine; Karolinska University Hospital, Department of Cardiology.
    Carrero, Juan-Jesus
    Karolinska Institute, Department of Clinical Science, Intervention and Technology.
    Farahmand, Bahman
    Epi-Consultant, Stockholm.
    Henriksson, Karin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. AstraZeneca RD, Mölndal.
    Jonsson, Asa
    County Hospital Ryhov, Division of Cardiology, Department of Medicine.
    Jernberg, Tomas
    Karolinska University Hospital, Department of Cardiology; Karolinska Institute, Department of Medical Epidemiology and Biostatistics.
    Dahlström, Ulf
    Linköping University, Department of Cardiology; Linköping University, Department of Medical and Health Sciences.
    Association between enrolment in a heart failure quality registry and subsequent mortality — a nationwide cohort study2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, no 9, p. 1107-1116Article in journal (Refereed)
    Abstract [en]

    Aims: Heart failure (HF) quality registries report quality of care but it is unknown whether they improve outcomes. The aims were to assess predictors of enrolment in a HF registry, test the hypothesis that enrolment in a HF registry is associated with reduced mortality, and assess potential explanatory factors for this reduction in mortality, if present.

    Methods and results: We conducted a nationwide prospective cohort study of patients with new-onset HF registered in the Swedish National Patient Registry (NPR, a mandatory registry of ICD-code diagnoses) with or without concurrent registration in the Swedish Heart Failure Registry (SwedeHF, a voluntary quality reporting registry) 2006–2013. The association between demographics, co-morbidities and medications, and enrolment in the SwedeHF, was assessed using multivariable logistic regression. The association between enrolment in the SwedeHF and all-cause mortality was assessed using multivariable Cox regression, with adjustment for demographics, co-morbidities and medications. A total of 231 437 patients were included, of which 21 888 (9.5%) were in the SwedeHF [age (mean ± standard deviation) 74 ± 13 years; 41% women; 68% inpatients] and 209 549 (90.5%) were not (age 78 ± 12 years, 50% women; 79% inpatients). Selected variables independently associated with enrolment in the SwedeHF were male sex, younger age, higher education, absent co-morbidities and co-morbidity-related medications, and use of HF and cardiovascular medications. Over a median (interquartile range) follow-up of 874 (247–1667) days, there were 13.0 vs. 20.8 deaths per 100 patient-years (P < 0.001). The hazard ratio (95% confidence interval) for death for the SwedeHF yes vs. no was 0.65 (0.63–0.66) crude, and increased to 0.80 (0.78–0.81) after adding demographics, to 0.82 (0.80–0.84) after adding co-morbidities and co-morbidity-related medications, to 0.95 (0.93–0.97) after adding cardiovascular medications, and to 1.04 (1.02–1.07) after adding HF-specific medications.

    Conclusion: Heart failure patients of male sex, younger age, and higher education were more likely to be enrolled in a HF quality registry. Enrolment was associated with reduced all-cause mortality that was explained by demographic differences and better utilization of cardiovascular and HF medications.

  • 304.
    Lundback, Magnus
    et al.
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden..
    Gasevic, Danijela
    Univ Edinburgh, Coll Med & Vet Med, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Rullman, Eric
    Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Ruge, Toralph
    Karolinska Univ Hosp, Dept Emergency Med, C1 63, S-14186 Stockholm, Sweden..
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Huddinge, Sweden.
    Holzmann, Martin J.
    Karolinska Univ Hosp, Dept Emergency Med, C1 63, S-14186 Stockholm, Sweden.;Karolinska Inst, Dept Internal Med, Stockholm, Sweden..
    Sex-specific risk of emergency department revisits and early readmission following myocardial infarction2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 243, p. 54-58Article in journal (Refereed)
    Abstract [en]

    Background: Readmissions within 30 days after hospitalization have been introduced as a measure of quality of care. There is a paucity of data regarding sex-specific risk of early readmissions after myocardial infarction (MI). Objectives: To investigate the association between sex and revisits to the emergency department (ED), and readmissions after MI. Methods: All patients with chest pain, diagnosed with MI at the Karolinska University Hospital during 2011 and 2012 were included. National Health care registers were used for information about patient characteristics, outcomes, and medication. We calculated risk ratios (RR) with 95% confidence intervals (CI) in women versus men, for revisits to the ED, readmission to hospital within 30, and 180 days, and to undergo coronary angiography, or revascularization, and to receive guideline-directed cardiovascular medication. Results: In total there were 667 patients with MI during the study period, of whom 197 (30%) were women. Womenwere older (mean age 73 vs. 65 years), and had more comorbidities thanmen. The 30-day risk of revisits to the ED was 1.56 times greater in women thanmen (adjusted RR 1.56 (1.09-2.25)). Throughout the first year; women were more likely to be readmitted than men, with the most striking difference found within 30 days (22% vs. 13%) of discharge (adjusted RR 1.54 (95% CI, 1.00-2.36)). There were no differences between men and women in new cardiovascular medication, coronary angiographies or revascularizations. Conclusions: Women have an increased risk of revisits to the ED, and readmissions to hospital during the first year after a MI.

  • 305.
    Lundberg, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    A comparison between different indices of carotid artery atherosclerosis at ultrasound regarding risk of incident myocardial infarction and stroke2015In: Article in journal (Other academic)
  • 306.
    Lundberg, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. AstraZeneca R&D, Mölndal, Sweden.
    The relationship between carotid intima-media thickness and global atherosclerosis2014In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 34, no 6, p. 457-462Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The aim of this study was to investigate the relationship between (i) carotid intima-media thickness (CIMT) at baseline as well as (ii) change in CIMT over 5 years (ΔCIMT) and atherosclerotically induced luminal narrowing in non-coronary arterial territories assessed by whole-body magnetic resonance angiography (WBMRA).

    METHODS AND RESULTS:

    In subgroups of the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS) study, US measurements of CIMT in the common carotid arteries were analysed at 70 and 75 years and ΔCIMT was calculated (n = 272). WBMRA, assessing arterial stenosis in five different territories by which also a total atherosclerotic score (TAS) was calculated, was performed at 70 years (n = 306).

    RESULTS:

    Carotid intima-media thickness in the carotid artery at baseline was correlated with TAS (P = 0·0001) when adjusted to a set of traditional risk factors for atherosclerosis, as well as to stenosis in two of the different investigated territories (aorta and lower leg, P = 0·013 and P = 0·004), but there was no significant correlation between ΔCIMT and TAS (P = 0·41).

    CONCLUSIONS:

    In the present study, CIMT, but not ΔCIMT over 5 years, in the carotid artery was related to overall stenoses in the body, as assessed by WBMRA. These findings support CIMT as a general marker for atherosclerosis.

  • 307.
    Lundberg, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ebeling Barbier, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Total atherosclerotic burden by whole body magnetic resonance angiography predicts major adverse cardiovascular events2013In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 228, no 1, p. 148-152Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    The purpose of the present study was to investigate the relationship between the Total Atherosclerotic Score (TAS), a measurement of the overall atherosclerotic burden of the arterial tree by whole body magnetic resonance angiography (WBMRA), and the risk of major adverse cardiovascular events (MACE), defined as cardiac death, myocardial infarction, stroke and/or coronary revascularization, assuming that TAS predicts MACE.

    METHODS AND RESULTS:

    305 randomly selected 70 year-old subjects (47% women) underwent WBMRA. Their atherosclerotic burden was evaluated and TAS > 0, that is atherosclerotic changes, were found in 68% of subjects. During follow-up (mean 4.8 years), MACE occurred in 25 subjects (8.2%). Adjusting for multiple risk factors, TAS was associated with MACE (OR 8.86 for any degree of vessel lumen abnormality, 95%CI 1.14-69.11, p = 0.037). In addition, TAS improved discrimination and reclassification when added to the Framingham risk score (FRS), and ROC (Receiver Operator Curve) increased from 0.681 to 0.750 (p = 0.0421).

    CONCLUSION:

    In a population-based sample of 70 year old men and women WBMRA, with TAS, predicted MACE independently of major cardiovascular risk factors.

  • 308.
    Lytsy, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    A proposal for an additional clinical trial outcome measure assessing preventive effect as delay of events2012In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 27, no 12, p. 903-909Article in journal (Refereed)
    Abstract [en]

    Many effect measures used in clinical trials are problematic because they are differentially understood by patients and physicians. The emergence of novel methods such as accelerated failure-time models and quantile regression has shifted the focus of effect measurement from probability measures to time-to-event measures. Such modeling techniques are rapidly evolving, but matching non-parametric descriptive measures are lacking. We propose such a measure, the delay of events, demonstrating treatment effect as a gain in event-free time. We believe this measure to be of value for shared clinical decision-making. The rationale behind the measure is given, and it is conceptually explained using the Kaplan–Meier estimate and the quantile regression framework. A formula for calculation of the delay of events is given. Hypothetical and empirical examples are used to demonstrate the measure. The measure is discussed in relation to other measures highlighting the time effects of preventive treatments. There is a need to further investigate the properties of the measure as well as its role in clinical decision-making.

  • 309.
    Lytsy, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Interplay of overweight and insulin resistance on hypertension development2014In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 32, no 4, p. 834-839Article in journal (Refereed)
    Abstract [en]

    Objectives: Obesity and hypertension are associated, possibly through causal pathways involving insulin resistance and metabolic derangements. We aimed to investigate in a whites sample if overweight or obese persons without insulin resistance are at risk of developing hypertension or blood pressure progression. Methods: In a meta-analysis, using multivariable-adjusted mixed-effects logistic regression models, we investigated the risks of hypertension development and blood pressure progression by combinations of relative weight classes and presence or absence of insulin resistance (defined as highest vs. lower three quartiles using the homeostatic model assessment method) in the Uppsala Longitudinal Study of Adult Men (n = 2322) and the Prospective Investigation of the Vasculature in Uppsala Seniors studies (n = 1066). These two samples, consisting mainly of middle-aged and elderly men, provided 1846 observations for the development of hypertension in normotensive individuals and 4223 observations for progressing to a higher blood pressure stage. Results: During a median of 10 years of follow-up, 884 (47.9%) developed hypertension and 1639 (38.8%) progressed to a higher blood pressure stage. Overweight or obese persons without insulin resistance had an increased risk of hypertension development [odds ratio (OR) 1.46, 95% confidence interval 1.14-1.88] and blood pressure progression (OR 1.32, 1.10-1.59) compared with normal-weight persons without insulin resistance. Conclusion: According to this study, being overweight or obese without insulin resistance increases the risk of hypertension and blood pressure progression. This adds to the evidence that overweight and obesity may be harmful per se, and that overweight and obesity without glucometabolic derangements are not benign conditions.

  • 310.
    Lytsy, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Endothelial function and risk of hypertension and blood pressure progression: the prospective investigation of the vasculature in Uppsala seniors2013In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 31, no 5, p. 936-939Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES

    Impaired endothelial function is associated with risk of cardiovascular events, possibly via increased blood pressure. We aimed to investigate if impaired endothelial function is associated with risk of hypertension and blood pressure progression in a large community-based sample.

    METHODS

    In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, endothelium-dependent vasodilation (EDV) was measured in resistance arteries using the invasive forearm technique and in conduit arteries using the flow-mediated vasodilation technique (FMD) at age 70, and participants were re-examined after 5 years. We investigated risk of developing hypertension or blood pressure progression in multivariable-adjusted logistic regression models.

    RESULTS

    In 201 out of 506 untreated persons, blood pressure progressed to a higher stage, and among 197 normotensive persons, 87 developed hypertension. Endothelial function, measured with the invasive forearm technique and the brachial ultrasound technique, did not predict either the development of hypertension [EDV: odds ratio (OR) per SD 1.16, 95% confidence interval (CI) 0.84-1.59; FMD: OR per SD 1.00, 95% CI 0.76-1.33) or blood pressure progression (EDV: OR per SD 0.90, 95% CI 0.73-1.11; FMD: OR per SD 1.01, 95% CI 0.84-1.21).

    CONCLUSION

    In this large community-based sample of elderly, impaired endothelial function measured with the invasive forearm technique did not play a major role in the development of hypertension or blood pressure progression. Observed associations between endothelial dysfunction and risk of cardiovascular events are likely mediated through other pathways than hypertension.

  • 311.
    Lövdahl, Susanna
    et al.
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Clin Coagulat Res Unit, SE-20502 Malmo, Sweden..
    Henriksson, Karin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. AstraZeneca, Dept Epidemiol, R&D, Molndal, Sweden..
    Baghaei, Fariba
    Sahlgrens Univ Hosp, Dept Med Hematol & Coagulat Disorders, Coagulat Ctr, Gothenburg, Sweden..
    Holmström, Margareta
    Karolinska Univ Hosp, Hematol Ctr, Coagulat Unit, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Berntorp, Erik
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Clin Coagulat Res Unit, SE-20502 Malmo, Sweden..
    Astermark, Jan
    Skane Univ Hosp, Dept Hematol & Coagulat Disorders, Malmo, Sweden..
    Malignancies in Swedish persons with haemophilia: a longitudinal registry study2016In: Blood Coagulation and Fibrinolysis, ISSN 0957-5235, E-ISSN 1473-5733, Vol. 27, no 6, p. 631-636Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to investigate, over time, the incidence of and mortality due to malignant diseases among persons with haemophilia, compared to matched controls. Persons with haemophilia A or B were enrolled via registries at each haemophilia centre, as well as from the National Patient Registry, and were compared to five sex and age-matched controls per patient. Data from the national Cancer Registry were linked to the study participants. A total of 1431 persons with haemophilia and 7150 matched controls were enrolled. Between the years 1972 and 2008, 164 malignancies were reported. The most common type of cancer among patients was prostate cancer, followed by haematologic malignancies, including lymphoma and leukaemia, which were significantly more frequent in patients [ n=35 (2.4%) vs. n=60 (0.8%); P < 0.001]. Malignancies in bladder and other urinary organs were also significantly different [ n=21 (1.5%) vs. n=46 (0.6%); P < 0.01]. The overall incidence rate ratio of malignancies per 1000 person-years compared to the controls was 1.3 [95% confidence interval (CI) 1.1, 1.6]. In subgroup analysis, the corresponding incidence rate ratios per 1000 person-years for persons with severe haemophilia was 1.7 (95% CI 0.9, 3.1) and that for mild/moderate haemophilia 1.1 (95% CI 0.8, 1.5). Swedish persons with haemophilia had a significantly higher incidence of malignant diseases than controls. These were primarily haematologic malignancies and cancer in urinary organs, and the difference independent of any co-infections with HIV and/or viral hepatitis. The findings indicate the importance of further studies and close follow-up of malignancies in persons with haemophilia.

  • 312. Maddock, Jane
    et al.
    Zhou, Ang
    Cavadino, Alana
    Kuźma, Elżbieta
    Bao, Yanchun
    Smart, Melissa C
    Saum, Kai-Uwe
    Schöttker, Ben
    Engmann, Jorgen
    Kjærgaard, Marie
    Karhunen, Ville
    Zhan, Yiqiang
    Lehtimäki, Terho
    Rovio, Suvi P
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lahti, Jari
    Marques-Vidal, Pedro
    Sen, Abhijit
    Perna, Laura
    Schirmer, Henrik
    Singh-Manoux, Archana
    Auvinen, Juha
    Hutri-Kähönen, Nina
    Kähönen, Mika
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Räikkönen, Katri
    Melhus, Håkan
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Guessous, Idris
    Petrovic, Katja E
    Schmidt, Helena
    Schmidt, Reinhold
    Vollenweider, Peter
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Eriksson, Johan G
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Raitakari, Olli T
    Hägg, Sara
    Pedersen, Nancy L
    Herzig, Karl-Heinz
    Järvelin, Marjo-Riitta
    Veijola, Juha
    Kivimaki, Mika
    Jorde, Rolf
    Brenner, Hermann
    Kumari, Meena
    Power, Chris
    Llewellyn, David J
    Hyppönen, Elina
    Vitamin D and cognitive function: A Mendelian randomisation study.2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 13230Article in journal (Refereed)
    Abstract [en]

    The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.

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  • 313. Maggio, Marcello
    et al.
    Cattabiani, Chiara
    Lauretani, Fulvio
    Mantovani, Marco
    Butto, Valeria
    De Vita, Francesca
    Volpi, Riccardo
    Artoni, Andrea
    Giallauria, Francesco
    Zuliani, Giovanni
    Aloe, Rosalia
    Lippi, Giuseppe
    Ceresini, Graziano
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ceda, Gian Paolo
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    SHBG and endothelial function in older subjects2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, no 3, p. 2825-2830Article in journal (Refereed)
    Abstract [en]

    Background: Endothelial dysfunction is predictor of cardiovascular diseases that have different prevalence in men and women before menopause. Sex hormones and sex hormone binding globulin (SHBG), novel risk factors for diabetes and cardiovascular diseases even in older individuals, might explain this difference. However, the relationship between these hormones and endothelial function has never been addressed in the elderly. Methods and results: 430 men and, 424 women 70 years older of Prospective Study of the Vasculature in Uppsala Seniors study, with complete data on SHBG, testosterone(T), estradiol(E2), endothelium-independent vasodilation (EIDV), endothelium-dependent vasodilation(EDV), flow-mediated vasodilation (FMD) and the pulse wave analysis (reflection index, RI) were evaluated. Multivariate regression analysis adjusted for confounders was used to assess the relationship between T, E2, SHBG and endothelial function. In men we found a positive relationship between SHBG and EDV (beta +/- SE 3.60 +/- 0.83, p < 0.0001), EIDV (2.42 +/- 0.58, p < 0.0001) but not with FMD. The relationship between SHBG and EDV and EIDV was maintained after adjustment for sex (1.64 +/- 0.47, p < 0.001 and 1.79 +/- 0.35, p < 0.0006, respectively). After adjustment for confounders, the relationship between SHBG and EDV and EIDV was still statistically significant (2.63 +/- 0.90 and 1.86 +/- 0.63, p = 0.004 for both). In women SHBG and EIDV were positively associated (1.58 +/- 0.46; p = 0.0007), and this relationship was independent of sex (1.79 +/- 0.35; p < 0.001). No significant interaction SHBG * SEX was found for EIDV (p = 0.72). In a combined analysis in two sexes, SHBG and EIDV were positively associated (1.13 +/- 0.45; p = 0.01). SHBG was not associated with EDV, FMD and RI. No significant relationship was found between T or E2 and EDV, EIDV, FMD or RI in both sexes. Conclusions: In older men SHBG, but not T and E2, is positively and independently associated with EDV in resistance arteries. In both sexes, SHBG was positively and independently associated with EIDV.

  • 314. Mahajan, Anubha
    et al.
    Go, Min Jin
    Zhang, Weihua
    Below, Jennifer E
    Gaulton, Kyle J
    Ferreira, Teresa
    Horikoshi, Momoko
    Johnson, Andrew D
    Ng, Maggie C Y
    Prokopenko, Inga
    Saleheen, Danish
    Wang, Xu
    Zeggini, Eleftheria
    Abecasis, Goncalo R
    Adair, Linda S
    Almgren, Peter
    Atalay, Mustafa
    Aung, Tin
    Baldassarre, Damiano
    Balkau, Beverley
    Bao, Yuqian
    Barnett, Anthony H
    Barroso, Ines
    Basit, Abdul
    Been, Latonya F
    Beilby, John
    Bell, Graeme I
    Benediktsson, Rafn
    Bergman, Richard N
    Boehm, Bernhard O
    Boerwinkle, Eric
    Bonnycastle, Lori L
    Burtt, Noel
    Cai, Qiuyin
    Campbell, Harry
    Carey, Jason
    Cauchi, Stephane
    Caulfield, Mark
    Chan, Juliana C N
    Chang, Li-Ching
    Chang, Tien-Jyun
    Chang, Yi-Cheng
    Charpentier, Guillaume
    Chen, Chien-Hsiun
    Chen, Han
    Chen, Yuan-Tsong
    Chia, Kee-Seng
    Chidambaram, Manickam
    Chines, Peter S
    Cho, Nam H
    Cho, Young Min
    Chuang, Lee-Ming
    Collins, Francis S
    Cornelis, Marilyn C
    Couper, David J
    Crenshaw, Andrew T
    van Dam, Rob M
    Danesh, John
    Das, Debashish
    de Faire, Ulf
    Dedoussis, George
    Deloukas, Panos
    Dimas, Antigone S
    Dina, Christian
    Doney, Alex S F
    Donnelly, Peter J
    Dorkhan, Mozhgan
    van Duijn, Cornelia
    Dupuis, Josee
    Edkins, Sarah
    Elliott, Paul
    Emilsson, Valur
    Erbel, Raimund
    Eriksson, Johan G
    Escobedo, Jorge
    Esko, Tonu
    Eury, Elodie
    Florez, Jose C
    Fontanillas, Pierre
    Forouhi, Nita G
    Forsen, Tom
    Fox, Caroline
    Fraser, Ross M
    Frayling, Timothy M
    Froguel, Philippe
    Frossard, Philippe
    Gao, Yutang
    Gertow, Karl
    Gieger, Christian
    Gigante, Bruna
    Grallert, Harald
    Grant, George B
    Groop, Leif C
    Groves, Christopher J
    Grundberg, Elin
    Guiducci, Candace
    Hamsten, Anders
    Han, Bok-Ghee
    Hara, Kazuo
    Hassanali, Neelam
    Hattersley, Andrew T
    Hayward, Caroline
    Hedman, Asa K
    Herder, Christian
    Hofman, Albert
    Holmen, Oddgeir L
    Hovingh, Kees
    Hreidarsson, Astradur B
    Hu, Cheng
    Hu, Frank B
    Hui, Jennie
    Humphries, Steve E
    Hunt, Sarah E
    Hunter, David J
    Hveem, Kristian
    Hydrie, Zafar I
    Ikegami, Hiroshi
    Illig, Thomas
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Islam, Muhammed
    Isomaa, Bo
    Jackson, Anne U
    Jafar, Tazeen
    James, Alan
    Jia, Weiping
    Jockel, Karl-Heinz
    Jonsson, Anna
    Jowett, Jeremy B M
    Kadowaki, Takashi
    Kang, Hyun Min
    Kanoni, Stavroula
    Kao, Wen Hong L
    Kathiresan, Sekar
    Kato, Norihiro
    Katulanda, Prasad
    Keinanen-Kiukaanniemi, Sirkka M
    Kelly, Ann M
    Khan, Hassan
    Khaw, Kay-Tee
    Khor, Chiea-Chuen
    Kim, Hyung-Lae
    Kim, Sangsoo
    Kim, Young Jin
    Kinnunen, Leena
    Klopp, Norman
    Kong, Augustine
    Korpi-Hyovalti, Eeva
    Kowlessur, Sudhir
    Kraft, Peter
    Kravic, Jasmina
    Kristensen, Malene M
    Krithika, S
    Kumar, Ashish
    Kumate, Jesus
    Kuusisto, Johanna
    Kwak, Soo Heon
    Laakso, Markku
    Lagou, Vasiliki
    Lakka, Timo A
    Langenberg, Claudia
    Langford, Cordelia
    Lawrence, Robert
    Leander, Karin
    Lee, Jen-Mai
    Lee, Nanette R
    Li, Man
    Li, Xinzhong
    Li, Yun
    Liang, Junbin
    Liju, Samuel
    Lim, Wei-Yen
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, Cecilia M
    Lindholm, Eero
    Liu, Ching-Ti
    Liu, Jian Jun
    Lobbens, Stephane
    Long, Jirong
    Loos, Ruth J F
    Lu, Wei
    Luan, Jian'an
    Lyssenko, Valeriya
    Ma, Ronald C W
    Maeda, Shiro
    Magi, Reedik
    Mannisto, Satu
    Matthews, David R
    Meigs, James B
    Melander, Olle
    Metspalu, Andres
    Meyer, Julia
    Mirza, Ghazala
    Mihailov, Evelin
    Moebus, Susanne
    Mohan, Viswanathan
    Mohlke, Karen L
    Morris, Andrew D
    Muhleisen, Thomas W
    Muller-Nurasyid, Martina
    Musk, Bill
    Nakamura, Jiro
    Nakashima, Eitaro
    Navarro, Pau
    Ng, Peng-Keat
    Nica, Alexandra C
    Nilsson, Peter M
    Njolstad, Inger
    Nothen, Markus M
    Ohnaka, Keizo
    Ong, Twee Hee
    Owen, Katharine R
    Palmer, Colin N A
    Pankow, James S
    Park, Kyong Soo
    Parkin, Melissa
    Pechlivanis, Sonali
    Pedersen, Nancy L
    Peltonen, Leena
    Perry, John R B
    Peters, Annette
    Pinidiyapathirage, Janani M
    Platou, Carl G P
    Potter, Simon
    Price, Jackie F
    Qi, Lu
    Radha, Venkatesan
    Rallidis, Loukianos
    Rasheed, Asif
    Rathmann, Wolfgang
    Rauramaa, Rainer
    Raychaudhuri, Soumya
    Rayner, N William
    Rees, Simon D
    Rehnberg, Emil
    Ripatti, Samuli
    Robertson, Neil
    Roden, Michael
    Rossin, Elizabeth J
    Rudan, Igor
    Rybin, Denis
    Saaristo, Timo E
    Salomaa, Veikko
    Saltevo, Juha
    Samuel, Maria
    Sanghera, Dharambir K
    Saramies, Jouko
    Scott, James
    Scott, Laura J
    Scott, Robert A
    Segre, Ayellet V
    Sehmi, Joban
    Sennblad, Bengt
    Shah, Nabi
    Shah, Sonia
    Shera, A Samad
    Shu, Xiao Ou
    Shuldiner, Alan R
    Sigurðsson, Gunnar
    Sijbrands, Eric
    Silveira, Angela
    Sim, Xueling
    Sivapalaratnam, Suthesh
    Small, Kerrin S
    So, Wing Yee
    Stancakova, Alena
    Stefansson, Kari
    Steinbach, Gerald
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen
    Strawbridge, Rona J
    Stringham, Heather M
    Sun, Qi
    Suo, Chen
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Takayanagi, Ryoichi
    Takeuchi, Fumihiko
    Tay, Wan Ting
    Teslovich, Tanya M
    Thorand, Barbara
    Thorleifsson, Gudmar
    Thorsteinsdottir, Unnur
    Tikkanen, Emmi
    Trakalo, Joseph
    Tremoli, Elena
    Trip, Mieke D
    Tsai, Fuu Jen
    Tuomi, Tiinamaija
    Tuomilehto, Jaakko
    Uitterlinden, Andre G
    Valladares-Salgado, Adan
    Vedantam, Sailaja
    Veglia, Fabrizio
    Voight, Benjamin F
    Wang, Congrong
    Wareham, Nicholas J
    Wennauer, Roman
    Wickremasinghe, Ananda R
    Wilsgaard, Tom
    Wilson, James F
    Wiltshire, Steven
    Winckler, Wendy
    Wong, Tien Yin
    Wood, Andrew R
    Wu, Jer-Yuarn
    Wu, Ying
    Yamamoto, Ken
    Yamauchi, Toshimasa
    Yang, Mingyu
    Yengo, Loic
    Yokota, Mitsuhiro
    Young, Robin
    Zabaneh, Delilah
    Zhang, Fan
    Zhang, Rong
    Zheng, Wei
    Zimmet, Paul Z
    Altshuler, David
    Bowden, Donald W
    Cho, Yoon Shin
    Cox, Nancy J
    Cruz, Miguel
    Hanis, Craig L
    Kooner, Jaspal
    Lee, Jong-Young
    Seielstad, Mark
    Teo, Yik Ying
    Boehnke, Michael
    Parra, Esteban J
    Chambers, John C
    Tai, E Shyong
    McCarthy, Mark I
    Morris, Andrew P
    Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 3, p. 234-244Article in journal (Refereed)
    Abstract [en]

    To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

  • 315.
    Mahajan, Anubha
    et al.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
    Rodan, Aylin R.
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75229 USA.
    Le, Thu H.
    Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
    Gaulton, Kyle J.
    Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
    Haessler, Jeffrey
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
    Stilp, Adrienne M.
    Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
    Kamatani, Yoichiro
    Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
    Zhu, Gu
    Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
    Sofer, Tamar
    Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
    Puri, Sanjana
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75229 USA.
    Schellinger, Jeffrey N.
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75229 USA.
    Chu, Pei-Lun
    Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
    Cechova, Sylvia
    Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
    van Zuydam, Natalie
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. School of Health and Social Studies, Dalarna University, Falun 791 88, Sweden.
    Flessner, Michael F.
    National Institute of Diabetes, Digestive, and Kidney Disease, NIH, Bethesda, MD 20892, USA.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Heath, Andrew C.
    Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, USA.
    Kubo, Michiaki
    Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7BN, UK.
    Madden, Pamela A. F.
    Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, USA.
    Montgomery, Grant W.
    Molecular Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
    Papanicolaou, George J.
    Epidemiology Branch, Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
    Reiner, Alex P.
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Thornton, Timothy A.
    Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
    Cai, Jianwen
    Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
    Martin, Nicholas G.
    Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
    Kooperberg, Charles
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
    Matsuda, Koichi
    Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
    Whitfield, John B.
    Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
    Okada, Yukinori
    Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
    Laurie, Cathy C.
    Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England; Department of Biostatistics, University of Liverpool, Liverpool L69 3GL, UK.
    Franceschini, Nora
    Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27514, USA.
    Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity2016In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 99, no 3, p. 636-646Article in journal (Refereed)
    Abstract [en]

    We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10(-8)) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of "credible sets" of variants driving eGFR association signals. Credible variants at the 20 eGFR loci were enriched for DNase I hypersensitivity sites (DHSs) in human kidney cells. DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues. Loss-of-function mutations in ancestral orthologs of both genes in Drosophila melanogaster were associated with altered sensitivity to salt stress. Renal mRNA expression of Nfatc1 and Rgs14 in a salt-sensitive mouse model was also reduced after exposure to a high-salt diet or induced CKD. Our study (1) demonstrates the utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect and (2) suggests that salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans.

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  • 316. Mahajan, Anubha
    et al.
    Sim, Xueling
    Ng, Hui Jin
    Manning, Alisa
    Rivas, Manuel A
    Highland, Heather M
    Locke, Adam E
    Grarup, Niels
    Im, Hae Kyung
    Cingolani, Pablo
    Flannick, Jason
    Fontanillas, Pierre
    Fuchsberger, Christian
    Gaulton, Kyle J
    Teslovich, Tanya M
    Rayner, N William
    Robertson, Neil R
    Beer, Nicola L
    Rundle, Jana K
    Bork-Jensen, Jette
    Ladenvall, Claes
    Blancher, Christine
    Buck, David
    Buck, Gemma
    Burtt, Noël P
    Gabriel, Stacey
    Gjesing, Anette P
    Groves, Christopher J
    Hollensted, Mette
    Huyghe, Jeroen R
    Jackson, Anne U
    Jun, Goo
    Justesen, Johanne Marie
    Mangino, Massimo
    Murphy, Jacquelyn
    Neville, Matt
    Onofrio, Robert
    Small, Kerrin S
    Stringham, Heather M
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Trakalo, Joseph
    Abecasis, Goncalo
    Bell, Graeme I
    Blangero, John
    Cox, Nancy J
    Duggirala, Ravindranath
    Hanis, Craig L
    Seielstad, Mark
    Wilson, James G
    Christensen, Cramer
    Brandslund, Ivan
    Rauramaa, Rainer
    Surdulescu, Gabriela L
    Doney, Alex S F
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Linneberg, Allan
    Isomaa, Bo
    Tuomi, Tiinamaija
    Jørgensen, Marit E
    Jørgensen, Torben
    Kuusisto, Johanna
    Uusitupa, Matti
    Salomaa, Veikko
    Spector, Timothy D
    Morris, Andrew D
    Palmer, Colin N A
    Collins, Francis S
    Mohlke, Karen L
    Bergman, Richard N
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Tuomilehto, Jaakko
    Hansen, Torben
    Watanabe, Richard M
    Prokopenko, Inga
    Dupuis, Josee
    Karpe, Fredrik
    Groop, Leif
    Laakso, Markku
    Pedersen, Oluf
    Florez, Jose C
    Morris, Andrew P
    Altshuler, David
    Meigs, James B
    Boehnke, Michael
    McCarthy, Mark I
    Lindgren, Cecilia M
    Gloyn, Anna L
    Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus2015In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, no 1, article id e1004876Article in journal (Refereed)
    Abstract [en]

    Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.

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  • 317.
    Mahajan, Anubha
    et al.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
    Wessel, Jennifer
    Indiana Univ, Diabet Translat Res Ctr, Dept Epidemiol, Indianapolis, IN 46204 USA;Indiana Univ, Diabet Translat Res Ctr, Dept Med, Indianapolis, IN 46204 USA.
    Willems, Sara M.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Zhao, Wei
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
    Robertson, Neil R.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
    Chu, Audrey Y.
    Natl Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA USA;Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
    Gan, Wei
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
    Kitajima, Hidetoshi
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
    Taliun, Daniel
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Rayner, N. William
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Guo, Xiuqing
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Li, Man
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Univ Utah, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA.
    Jensen, Richard A.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
    Hu, Yao
    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Shanghai, Peoples R China.
    Huo, Shaofeng
    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Shanghai, Peoples R China.
    Lohman, Kurt K.
    Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Dept Biostatist Sci, Winston Salem, NC USA.
    Zhang, Weihua
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, London, Middx, England.
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Prins, Bram Peter
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Flannick, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
    Trubetskoy, Vassily Vladimirovich
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Kravic, Jasmina
    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
    Kim, Young Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
    Rybin, Denis V.
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
    Yaghootkar, Hanieh
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
    Mueller-Nurasyid, Martina
    Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Partner Site, Munich, Germany.
    Meidtner, Karina
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, Nuthetal, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Li-Gao, Ruifang
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Varga, Tibor V.
    Lund Univ, Genet & Mol Epidemiol Unit, Diabet Ctr, Dept Clin Sci, Malmo, Sweden.
    Marten, Jonathan
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Li, Jin
    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Smith, Albert Vernon
    Iceland Heart Assoc, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    An, Ping
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Ligthart, Symen
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Malerba, Giovanni
    Univ Verona, Dept Neurosci Biomed & Movement Sci, Sect Biol & Genet, Verona, Italy.
    Demirkan, Ayse
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
    Tajes, Juan Fernandez
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
    Steinthorsdottir, Valgerdur
    deCODE Genet Amgen Inc, Reykjavik, Iceland.
    Wuttke, Matthias
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Med Ctr, Freiburg, Germany.
    Lecoeur, Cecile
    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France.
    Preuss, Michael
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Bielak, Lawrence F.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Graff, Marielisa
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
    Highland, Heather M.
    Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Human Genet Ctr, Houston, TX 77030 USA.
    Justice, Anne E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
    Liu, Dajiang J.
    Penn State Coll Med, Inst Personalized Med, Dept Publ Hlth Sci, Hershey, PA USA.
    Marouli, Eirini
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
    Peloso, Gina Marie
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
    Warren, Helen R.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England;Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England.
    Afaq, Saima
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.
    Afzal, Shoaib
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
    Ahlqvist, Emma
    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
    Almgren, Peter
    Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden.
    Amin, Najaf
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Bang, Lia B.
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark.
    Bertoni, Alain G.
    Wake Forest Univ Hlth Sci, Dept Epidemiol & Prevent, Publ Hlth Sci, Winston Salem, NC USA.
    Bombieri, Cristina
    Univ Verona, Dept Neurosci Biomed & Movement Sci, Sect Biol & Genet, Verona, Italy.
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
    Brandslund, Ivan
    Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark;Vejle Hosp, Dept Clin Biochem, Vejle, Denmark.
    Brody, Jennifer A.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
    Burtt, Noel P.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
    Canouil, Mickael
    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France.
    Chen, Yii-Der Ida
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Cho, Yoon Shin
    Hallym Univ, Dept Biomed Sci, Chunchon, South Korea.
    Christensen, Cramer
    Lillebaelt Hosp Vejle, Med Dept, Vejle, Denmark.
    Eastwood, Sophie V.
    UCL, Inst Cardiovasc Sci, London, England.
    Eckardt, Kai-Uwe
    Charite Univ Med Berlin, Dept Nephrol & Med Intens Care, Berlin, Germany.
    Fischer, Krista
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Gambaro, Giovanni
    Univ Cattolica Sacro Cuore, Inst Internal & Geriatr Med, Rome, Italy.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Grove, Megan L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA.
    de Haan, Hugoline G.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Hackinger, Sophie
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Hai, Yang
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Han, Sohee
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
    Tybjaerg-Hansen, Anne
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark.
    Hivert, Marie-France
    Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA;Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA;Univ Sherbrooke, Dept Med, Sherbrooke, PQ, Canada.
    Isomaa, Bo
    Malmska Municipal Hlth Care Ctr & Hosp, Pietarsaari, Finland;Folkhalsan Res Ctr, Helsinki, Finland.
    Jager, Susanne
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, Nuthetal, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Jorgensen, Marit E.
    Steno Diabet Ctr Copenhagen, Gentofte, Denmark;Southern Denmark Univ, Natl Inst Publ Hlth, Copenhagen, Denmark.
    Jorgensen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Res Ctr Prevent & Hlth, Glostrup, Denmark;Aalborg Univ, Fac Med, Aalborg, Denmark.
    Karajamaki, Annemari
    Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland;Vaasa Hlth Care Ctr, Diabet Ctr, Vaasa, Finland.
    Kim, Bong-Jo
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
    Kim, Sung Soo
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
    Koistinen, Heikki A.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland;Helsinki Univ Hosp, Abdominal Ctr, Endocrinol, Helsinki, Finland;Minerva Fdn, Helsinki, Finland;Univ Helsinki, Dept Med, Helsinki, Finland;Univ Helsinki, Cent Hosp, Helsinki, Finland.
    Kovacs, Peter
    Univ Leipzig, Ctr Adipos Dis, Integrated Res & Treatment IFB, Leipzig, Germany.
    Kriebel, Jennifer
    German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Res Unit Mol Epidemiol, Neuherberg, Germany.
    Kronenberg, Florian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Lall, Kristi
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia;Univ Tartu, Inst Math Stat, Tartu, Estonia.
    Lange, Leslie A.
    Univ Colorado Denver, Div Bioinformat & Personalized Med, Dept Med, Aurora, CO USA.
    Lee, Jung-Jin
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
    Lehne, Benjamin
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.
    Li, Huaixing
    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Shanghai, Peoples R China.
    Lin, Keng-Hung
    Taichung Vet Gen Hosp, Dept Ophthalmol, Taichung, Taiwan.
    Linneberg, Allan
    Res Ctr Prevent & Hlth, Glostrup, Denmark;Rigshosp, Dept Clin Expt Res, Glostrup, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
    Liu, Jun
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Loh, Marie
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;Univ Oulu, Inst Hlth Sci, Oulu, Finland;ASTAR, TLGM, Singapore, Singapore.
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Mamakou, Vasiliki
    Univ Athens, Dromokaiteio Psychiat Hosp, Athens, Greece.
    McKean-Cowdin, Roberta
    Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
    Nadkarni, Girish
    Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA.
    Neville, Matt
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Nielsen, Sune F.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
    Ntalla, Ioanna
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
    Peyser, Patricia A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Rathmann, Wolfgang
    German Ctr Diabet Res DZD, Neuherberg, Germany;Univ Dusseldorf, Leibniz Ctr Diabet Res Heinrich Heine, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany.
    Rice, Kenneth
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Rich, Stephen S.
    Univ Virginia, Sch Med, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
    Rode, Line
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark.
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Schonherr, Sebastian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Selvin, Elizabeth
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Small, Kerrin S.
    Kings Coll London, Dept Twins Res & Genet Epidemiol, London, England.
    Stancakova, Alena
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Surendran, Praveen
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.
    Taylor, Kent D.
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Teslovich, Tanya M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Thorand, Barbara
    German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.
    Thorleifsson, Gudmar
    deCODE Genet Amgen Inc, Reykjavik, Iceland.
    Tin, Adrienne
    Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
    Tonjes, Anke
    Univ Leipzig, Dept Med, Leipzig, Germany.
    Varbo, Anette
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark.
    Witte, Daniel R.
    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark;Danish Diabet Acad, Odense, Denmark.
    Wood, Andrew R.
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
    Yajnik, Pranav
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Yao, Jie
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Yengo, Loic
    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France.
    Young, Robin
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Amouyel, Philippe
    Univ Lille Nord France, INSERM, U1167, Inst Pasteur Lille, Lille, France.
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Epidemiol, Nuthetal, Germany.
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Chowdhury, Rajiv
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
    Collins, Francis S.
    NHGRI, US Natl Inst Hlth, Genome Technol Branch, Bethesda, MD 20892 USA.
    Dedoussis, George
    Harokopio Univ Athens, Dept Nutr & Dietet, Athens, Greece.
    Dehghan, Abbas
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;German Ctr Diabet Res DZD, Neuherberg, Germany;Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia.
    Ferrario, Marco M.
    Univ Insubria, Dept Med & Surg, Res Ctr Epidemiol & Prevent Med EPIMED, Varese, Italy.
    Ferrieres, Jean
    INSERM, UMR 1027, Toulouse, France;Toulouse Univ, Sch Med, Dept Cardiol, Toulouse, France.
    Florez, Jose C.
    Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA;Harvard Med Sch, Dept Med, Boston, MA USA.
    Frossard, Philippe
    Ctr Noncommunicable Dis, Karachi, Pakistan.
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Harris, Tamara B.
    US Natl Inst Hlth, Natl Inst Aging, Laboratory Epidemiol & Populat Sci, Bethesda, MD USA.
    Heckbert, Susan R.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kathiresan, Sekar
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA;Harvard Med Sch, Dept Med, Boston, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
    Kee, Frank
    Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth NI, Belfast, Antrim, North Ireland.
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Launer, Lenore J.
    US Natl Inst Hlth, Natl Inst Aging, Laboratory Epidemiol & Populat Sci, Bethesda, MD USA.
    Lindgren, Cecilia M.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England.
    Mannisto, Satu
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, Munich, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Human Genet, Neuherberg, Germany.
    Melander, Olle
    Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden.
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
    Moitry, Marie
    Univ Strasbourg, Dept Epidemiol & Publ Hlth, Strasbourg, France;Univ Hosp Strasbourg, Dept Publ Hlth, Strasbourg, France.
    Morris, Andrew D.
    Ninewells Hosp, Ctr Mol Med, Clin Res Ctr, Dundee, Scotland;Med Sch, Dundee, Scotland;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Murray, Alison D.
    Univ Aberdeen, Sch Med Med Sci & Nutr, Aberdeen Biomed Imaging Ctr, Aberdeen, Scotland.
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci Diabet & Cardiovasc Dis, Genet Epidemiol, Malmo, Sweden.
    Owen, Katharine R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Perola, Markus
    Natl Inst Hlth & Welf, Helsinki, Finland;Univ Helsinki, FIMM, Helsinki, Finland.
    Peters, Annette
    DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Partner Site, Munich, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.
    Province, Michael A.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Rasheed, Asif
    Ctr Noncommunicable Dis, Karachi, Pakistan.
    Ridker, Paul M.
    Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA USA.
    Rivadineira, Fernando
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
    Rosendaal, Frits R.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Rosengren, Anders H.
    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Sheu, Wayne H. -H.
    Taichung Vet Gen Hosp, Dept Internal Med, Taichung, Taiwan;Natl Yang Ming Univ, Sch Med, Taipei, Taiwan;Sch Med, Natl Def Med Ctr, Taipei, Taiwan.
    Sladek, Rob
    McGill Univ, Montreal, PQ, Canada;Genome Quebec Innovat Ctr, Montreal, PQ, Canada;McGill Univ, Dept Human Genet, Montreal, PQ, Canada;McGill Univ, Dept Med, Div Endocrinol & Metab, Montreal, PQ, Canada.
    Smith, Blair H.
    Univ Dundee, Ninewells Hosp, Div Populat Hlth Sci, Dundee, Scotland;Univ Dundee, Med Sch, Dundee, Scotland.
    Strauch, Konstantin
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
    Uitterlinden, Andre G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Varma, Rohit
    Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA 90033 USA.
    Willer, Cristen J.
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA;Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
    Bluher, Matthias
    Univ Leipzig, Ctr Adipos Dis, Integrated Res & Treatment IFB, Leipzig, Germany;Univ Leipzig, Dept Med, Leipzig, Germany.
    Butterworth, Adam S.
    German Ctr Diabet Res DZD, Neuherberg, Germany;Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England.
    Chambers, John Campbell
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, London, Middx, England;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England.
    Chasman, Daniel I.
    Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA USA.
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England;Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England;Univ Cambridge, Dept Med, British Heart Fdn, Cambridge Ctr Excellence, Cambridge, England.
    van Duijn, Cornelia
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Dupuis, Josee
    Natl Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA USA;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
    Franco, Oscar H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Franks, Paul W.
    Lund Univ, Genet & Mol Epidemiol Unit, Diabet Ctr, Dept Clin Sci, Malmo, Sweden;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.
    Froguel, Philippe
    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England.
    Grallert, Harald
    German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Res Unit Mol Epidemiol, Neuherberg, Germany;Ludwig Maximillians Univ Munich, Helmholtz Zentrum Munchen, Clin Cooperat Grp Type Diabet 2, Munich, Germany;Tech Univ Munich, Clin Cooperat Grp Nutrigen & Type Diabet 2, Helmholtz Zentrum Munchen, Munich, Germany.
    Groop, Leif
    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden;Univ Helsinki, FIMM, Helsinki, Finland.
    Han, Bok-Ghee
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark.
    Hattersley, Andrew T.
    Univ Exeter, Med Sch, Exeter, Devon, England.
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Kardia, Sharon L. R.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Kooner, Jaspal Singh
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, London, Middx, England;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England;Imperial Coll London, Natl Heart & Lung Inst, Cardiovasc Sci, Hammersmith Campus, London, England.
    Kottgen, Anna
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Med Ctr, Freiburg, Germany.
    Kuulasmaa, Kari
    Tech Univ Munich, Inst Human Genet, Munich, Germany.
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Lin, Xu
    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Shanghai, Peoples R China.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Liu, Yongmei
    Wake Forest Univ Hlth Sci, Dept Epidemiol & Prevent, Publ Hlth Sci, Winston Salem, NC USA.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
    Marchini, Jonathan
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Dept Stat, Oxford, England.
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Mook-Kanamori, Dennis
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands.
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp, Pat Macpherson Ctr Pharmacogenet & Pharmacogenom, Dundee, Scotland;Univ Dundee, Med Sch, Dundee, Scotland. Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Pankow, James S.
    Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA.
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
    Psaty, Bruce M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Schulze, Matthias B.
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, Nuthetal, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Soranzo, Nicole
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England;Univ Cambridge, Sch Clin Med, Dept Hematol, Cambridge, England.
    Spector, Timothy D.
    Kings Coll London, Dept Twins Res & Genet Epidemiol, London, England.
    Stefansson, Kari
    Univ Iceland, Fac Med, Reykjavik, Iceland;deCODE Genet Amgen Inc, Reykjavik, Iceland.
    Stumvoll, Michael
    Univ Hosp Leipzig, Div Endocrinol, Leipzig, Germany;Univ Hosp Leipzig, Div Nephrol, Leipzig, Germany.
    Thorsteinsdottir, Unnur
    Univ Iceland, Fac Med, Reykjavik, Iceland;deCODE Genet Amgen Inc, Reykjavik, Iceland.
    Tuomi, Tiinamaija
    Folkhalsan Res Ctr, Helsinki, Finland;Helsinki Univ Hosp, Abdominal Ctr, Endocrinol, Helsinki, Finland;Univ Helsinki, FIMM, Helsinki, Finland;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland.
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland;Dasman Diabet Inst, Dasman, Kuwait;Danube Univ Krems, Dept Neurosci & Prevent Med, Krems, Austria;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Barroso, Ines
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England;Univ Cambridge, Wellcome Trust MRC Inst Metab Sci, Metabol Res Labs, Cambridge, England.
    Frayling, Timothy M.
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
    Goodarzi, Mark O.
    Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.
    Meigs, James B.
    Harvard Med Sch, Dept Med, Boston, MA USA;Harvard Med Sch, Massachusetts Gen Hosp, Gen Med Div, Boston, MA USA.
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Saleheen, Danish
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA;Ctr Noncommunicable Dis, Karachi, Pakistan.
    Morris, Andrew P.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Rotter, Jerome I.
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA;Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Med,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    McCarthy, Mark I.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes2018In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 4, p. 559-571Article in journal (Refereed)
    Abstract [en]

    We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 x 10(-7)); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio <= 1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.

  • 318.
    Malik, Rainer
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    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany.
    Chauhan, Ganesh
    Indian Inst Sci, Ctr Brain Res, Bangalore, Karnataka, India;Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France.
    Traylor, Matthew
    Univ Cambridge, Div Clin Neurosci, Stroke Res Grp, Cambridge, England.
    Sargurupremraj, Muralidharan
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France;NUI Galway, Dept Med, Clin Res Facil, Galway, Ireland.
    Okada, Yukinori
    RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan;Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan;Osaka Univ, Immunol Frontier Res Ctr WPI IFReC, Lab Stat Immunol, Suita, Osaka, Japan;Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
    Mishra, Aniket
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France.
    Rutten-Jacobs, Loes
    Univ Cambridge, Div Clin Neurosci, Stroke Res Grp, Cambridge, England.
    Giese, Anne-Katrin
    Harvard Med Sch, MGH, Dept Neurol, Boston, MA USA.
    van der Laan, Sander W.
    Univ Utrecht, Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol,Dept Cardiol, Utrecht, Netherlands.
    Gretarsdottir, Solveig
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland.
    Anderson, Christopher D.
    MGH, Ctr Genom Med, Boston, MA USA;MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
    Chong, Michael
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Adams, Hieab H. H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Erasmus Univ, Med Ctr, Dept Radiol & Nucl Med, Rotterdam, Netherlands.
    Ago, Tetsuro
    Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka, Japan.
    Almgren, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Amouyel, Philippe
    Univ Lille, Risk Factors & Mol Determinants Aging Related Dis, Inst Pasteur Lille, INSERM,LabEx DISTALZ,UMR1167, Lille, France;CHU Lille, Epidemiol & Publ Hlth Dept, Lille, France.
    Ay, Hakan
    MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA;Harvard Med Sch, MGH, Dept Radiol, AA Martinos Ctr Biomed Imaging, Boston, MA USA.
    Bartz, Traci M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Biostat, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA.
    Benavente, Oscar R.
    Univ British Columbia, Brain Res Ctr, Div Neurol, Fac Med, Vancouver, BC, Canada.
    Bevan, Steve
    Univ Lincoln, Sch Life Sci, Lincoln, England.
    Boncoraglio, Giorgio B.
    IRCCS, Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy.
    Brown, Robert D., Jr.
    Mayo Clin, Dept Neurol, Rochester, MN USA.
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Natl Inst Hlth Res Blood, Cambridge, England;Univ Cambridge, Transplant Res Unit Donor Hlth & Gen, Cambridge, England.
    Carrera, Caty
    Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Neurol Dept, Barcelona, Spain;Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Med Dept, Barcelona, Spain;Fundacio Docencia & Recerca MutuaTerrassa, Stroke Pharmacogen & Genet, Recerca MutuaTerrassa, Terrassa, Spain.
    Carty, Cara L.
    Childrens Natl Med Ctr, Childrens Res Inst, Washington, DC 20010 USA;George Washington Univ, Ctr Translat Sci, Washington, DC USA.
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Chen, Wei-Min
    Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    Cole, John W.
    Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA;Baltimore VAMC, Baltimore, MD USA.
    Correa, Adolfo
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA;Univ Mississippi, Med Ctr, Dept Pediat, Jackson, MS 39216 USA;Univ Mississippi, Med Ctr, Dept Populat Hlth Sci, Jackson, MS 39216 USA.
    Cotlarciuc, Ioana
    Royal Holloway Univ London, Inst Cardiovasc Res, London, England;Ashford, Surrey, England;St Peters Hosp, Surrey, England.
    Cruchaga, Carlos
    Washington Univ, Sch Med, Dept Psychiat, Hope Ctr Program Prot Aggregat & Neurodegenerat H, St Louis, MO 63110 USA;Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA.
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England;Wellcome Trust Sanger Inst, Cambridge, England;Univ Cambridge, Dept Med, British Heart Fdn, Cambridge Ctr Excellence, Cambridge, England.
    de Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands.
    DeStefano, Anita L.
    Boston Univ, Sch Publ Hlth, Boston, MA USA;Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
    den Hoed, Marcel
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Duan, Qing
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
    Engelter, Stefan T.
    Basel Univ Hosp, Dept Neurol, Basel, Switzerland;Basel Univ Hosp, Stroke Ctr, Basel, Switzerland;Univ Basel, Neurorehabilitat Unit, Basel, Switzerland;Univ Ctr Med Aging & Rehabil Basel, Felix Platter Hosp, Basel, Switzerland.
    Falcone, Guido J.
    Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA;Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
    Gottesman, Rebecca F.
    Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
    Grewal, Raji P.
    SF Med Ctr, Neurosci Inst, Trenton, NJ USA.
    Gudnason, Vilmundur
    Iceland Heart Assoc Res Inst, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Haessler, Jeffrey
    SF Med Ctr, Neurosci Inst, Trenton, NJ USA.
    Harris, Tamara B.
    NIH, Natl Inst Aging, Lab Epidemiol & Populat Sci, Bldg 10, Bethesda, MD 20892 USA.
    Hassan, Ahamad
    Leeds Teaching Hosp NHS Trust, Leeds Gen Infirm, Dept Neurol, Leeds, W Yorkshire, England.
    Havulinna, Aki S.
    Natl Inst Hlth & Welf, Helsinki, Finland;Inst Mol Med Finland, FIMM, Helsinki, Finland.
    Heckbert, Susan R.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
    Holliday, Elizabeth G.
    Hunter Med Res Inst, Publ Hlth Stream, New Lambton, NSW, Australia;Univ Newcastle, Fac Hlth & Med, Newcastle, NSW, Australia.
    Howard, George
    Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA.
    Hsu, Fang-Chi
    Wake Forest Sch Med, Dept Biostat, Winston Salem, NC USA.
    Hyacinth, Hyacinth I.
    Emory Univ, Sch Med, Dept Pediat, Aflac Canc & Blood Disorder Ctr, Atlanta, GA USA.
    Ikram, M. Arfan
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA USA..
    Irvin, Marguerite R.
    Univ Alabama Birmingham, Sch Publ Hlth, Epidemiol, Birmingham, AL 35294 USA.
    Jian, Xueqiu
    Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA.
    Jimenez-Conde, Jordi
    Univ Autonoma Barcelona, Inst Hosp Mar Invest Med, Neurol Dept, Neurovasc Res Grp NEUVAS, Barcelona, Spain.
    Johnson, Julie A.
    Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA;Univ Florida, Coll Pharm, Ctr Pharmacogen, Gainesville, FL USA;Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA.
    Jukema, J. Wouter
    Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
    Kanai, Masahiro
    RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan;Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan;Harvard Med Sch, Program Bioinformat & Integrat Gen, Boston, MA USA.
    Keene, Keith L.
    East Carolina Univ, Dept Biol, Greenville, NC USA;East Carolina Univ, Ctr Hlth Dispar, Greenville, NC USA.
    Kissela, Brett M.
    Univ Cincinnati, Coll Med, Cincinnati, OH USA.
    Kleindorfer, Dawn O.
    Univ Cincinnati, Coll Med, Cincinnati, OH USA.
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
    Kubo, Michiaki
    RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan.
    Lange, Leslie A.
    Univ Colorado Denver, Dept Med, Anschutz Med Campus, Aurora, CO USA.
    Langefeld, Carl D.
    Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Launer, Lenore J.
    NIH, Natl Inst Aging, Intramural Res Program, Bldg 10, Bethesda, MD 20892 USA.
    Lee, Jin-Moo
    Washington Univ, Sch Med, Dept Neurol Radiol & Biomed Engn, St Louis, MO USA.
    Lemmens, Robin
    Univ Leuven, KU Leuven, Dept Neurosci Expt Neurol, Leuven, Belgium;Univ Hosp Leuven, Dept Neurol, VIB Ctr Brain & Dis Res, Leuven, Belgium.
    Leys, Didier
    Univ Lille, CHU Lille, INSERM, U 1171, Lille, France.
    Lewis, Cathryn M.
    Kings Coll London, Dept Med & Mol Genet, London, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, SGDP Ctr, London, England.
    Lin, Wei-Yu
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Newcastle Univ, Northern Inst Canc Res, Newcastle, NSW, Australia.
    Lindgren, Arne G.
    Lund Univ, Dept Clin Sci Lund, Neurol, Lund, Sweden;Skane Univ Hosp, Dept Neurol & Rehabil Med, Lund, Sweden.
    Lorentzen, Erik
    Univ Gothenburg, Bioinformat Core Facil, Gothenburg, Sweden.
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Maguire, Jane
    Univ Technol Sydney, Fac Hlth, Ultimo, NSW, Australia.
    Manichaikul, Ani
    Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    McArdle, Patrick F.
    Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
    Meschia, James F.
    Mayo Clin, Dept Neurol, Jacksonville, FL USA.
    Mitchell, Braxton D.
    Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA;Baltimore Vet Adm, Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA.
    Mosley, Thomas H.
    Univ Mississippi, Med Ctr, Sch Med, Div Geriatr, Jackson, MS 39216 USA;Univ Mississippi, Med Ctr, Memory Impairment & Neurodegenerat Dementia Ctr, Jackson, MS 39216 USA.
    Nalls, Michael A.
    NIH, Natl Inst Aging, Lab Neurogenet, Bldg 10, Bethesda, MD 20892 USA;Data Tecn Int, Glen Echo, MD USA.
    Ninomiya, Toshiharu
    Kyushu Univ, Grad Sch Med Sci, Dept Epidemiol & Publ Hlth, Fukuoka, Japan.
    O'Donnell, Martin J.
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada;NUI Galway, Dept Med, Clin Res Facil, Galway, Ireland.
    Psaty, Bruce M.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Pulit, Sara L.
    Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands;Univ Med Ctr Utrecht, Dept Neurol, Brain Ctr Rudolf Magnus, Utrecht, Netherlands.
    Rannikmae, Kristiina
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland.
    Reiner, Alexander P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
    Rexrode, Kathryn M.
    Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
    Rice, Kenneth
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Rich, Stephen S.
    Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Rost, Natalia S.
    Harvard Med Sch, MGH, Dept Neurol, Boston, MA USA;MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA.
    Rothwell, Peter M.
    Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England.
    Rotter, Jerome I.
    Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA;Harbor UCLA, Med Ctr, Dept Pediat, Div Genom Outcomes, Torrance, CA USA.
    Rundek, Tatjana
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
    Sacco, Ralph L.
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
    Sakaue, Saori
    Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan;Univ Tokyo, Grad Sch Med, Dept Allergy & Rheumatol, Tokyo, Japan.
    Sale, Michele M.
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA.
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Sapkota, Bishwa R.
    Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, Oklahoma City, OK 73190 USA.
    Schmidt, Reinhold
    Med Univ Graz, Dept Neurol, Graz, Austria.
    Schmidt, Carsten O.
    Univ Med Greifswald, SHIP KEF, Inst Community Med, Greifswald, Germany.
    Schminke, Ulf
    Univ Med Greifswald, Dept Neurol, Greifswald, Germany.
    Sharma, Pankaj
    Royal Holloway Univ London, Inst Cardiovasc Res, London, England;Ashford, Surrey, England;St Peters Hosp, Surrey, England.
    Slowik, Agnieszka
    Jagiellonian Univ, Dept Neurol, Krakow, Poland.
    Sudlow, Cathie L. M.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland.
    Tanislav, Christian
    Justus Liebig Univ, Dept Neurol, Giessen, Germany.
    Tatlisumak, Turgut
    Univ Gothenburg, Sahlgrenska Acad, Inst Neuroscience & Physiol, Dept Clin Neurosci Neurol, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Taylor, Kent D.
    Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA;Harbor UCLA, Med Ctr, Dept Pediat, Div Genom Outcomes, Torrance, CA USA.
    Thijs, Vincent N. S.
    Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Stroke Div, Heidelberg, Vic, Australia;Austin Hlth, Dept Neurol, Heidelberg, Vic, Australia.
    Thorleifsson, Gudmar
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland.
    Thorsteinsdottir, Unnur
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland.
    Tiedt, Steffen
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany.
    Trompet, Stella
    Leiden Univ, Med Ctr, Sect Gerontol & Geriatr, Dept Internal Med, Leiden, Netherlands.
    Tzourio, Christophe
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Dept Publ Hlth, Bordeaux, France.
    van Duijn, Cornelia M.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands;Ctr Med Syst Biol, Leiden, Netherlands.
    Walters, Matthew
    Univ Glasgow, Sch Med Dent & Nursing, Glasgow, Lanark, Scotland.
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Wassertheil-Smoller, Sylvia
    Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Wiggins, Kerri L.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    Yang, Qiong
    Boston Univ, Sch Publ Hlth, Boston, MA USA.
    Yusuf, Salim
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    Pastinen, Tomi
    McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
    Ruusalepp, Arno
    Univ Tartu, Inst Biomed & Translat Med, Dept Pathophysiol, Tartu, Estonia;Tartu Univ Hosp, Dept Cardiac Surg, Tartu, Estonia;Clin Gene Networks AB, Stockholm, Sweden.
    Schadt, Eric E.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Koplev, Simon
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Bjorkegren, Johan L. M.
    Clin Gene Networks AB, Stockholm, Sweden;Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Univ Tartu, Biomeedikum, Inst Biomedicine & Translat Med, Dept Pathophysiol, Tartu, Estonia;Karolinska Univ Ssjukhuset, Dept Med, Integrated Cardio Metab Ctr, Huddinge, Sweden.
    Codoni, Veronica
    Sorbonne Univ, UPMC Univ Paris 06, Team Genom & Pathophysiol Cardiovasc Dis, INSERM,UMR S 1166, Paris, France;CAN Inst Cardiometab & Nutr, Paris, France.
    Civelek, Mete
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA;Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA.
    Smith, Nicholas L.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA;VA Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
    Tregouet, David A.
    Sorbonne Univ, UPMC Univ Paris 06, Team Genom & Pathophysiol Cardiovasc Dis, INSERM,UMR S 1166, Paris, France;CAN Inst Cardiometab & Nutr, Paris, France.
    Christophersen, Ingrid E.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MGH, Cardiovasc Res Ctr, Boston, MA USA;Vestre Viken Hosp Trust, Baerum Hosp, Dept Med Res, Gjettum, Norway.
    Roselli, Carolina
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
    Lubitz, Steven A.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MGH, Cardiovasc Res Ctr, Boston, MA USA.
    Ellinor, Patrick T.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MGH, Cardiovasc Res Ctr, Boston, MA USA.
    Tai, E. Shyong
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore.
    Kooner, Jaspal S.
    Imperial Coll London, Natl Heart & Lung Inst, London, England.
    Kato, Norihiro
    Natl Ctr Global Hlth & Med, Res Inst, Dept Gene Diagnost & Therapeut, Tokyo, Japan.
    He, Jiang
    Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, London, England;Imperial Coll London, NIHR Imperial Biomed Res Ctr, London, England.
    Chambers, John C.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.
    Takeuchi, Fumihiko
    Natl Ctr Global Hlth & Med, Res Inst, Dept Gene Diagnost & Therapeut, Tokyo, Japan.
    Johnson, Andrew D.
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA;Natl Heart Lung & Blood Res Inst, Div Intramural Res, Populat Sci Branch, Framingham, MA USA.
    Sanghera, Dharambir K.
    Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, Oklahoma City, OK 73190 USA;Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73190 USA;Oklahoma Ctr Neurosci, Oklahoma City, OK USA.
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Jern, Christina
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Pathol & Genet, Gothenburg, Sweden.
    Strbian, Daniel
    Helsinki Univ Hosp, Dept Neurol, Helsinki, Finland;Univ Helsinki, Clin Neurosci, Neurol, Helsinki, Finland.
    Fernandez-Cadenas, Israel
    Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Neurol Dept, Barcelona, Spain;Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Med Dept, Barcelona, Spain;Fundacio Docencia & Recerca MutuaTerrassa, Stroke Pharmacogen & Genet, Recerca MutuaTerrassa, Terrassa, Spain.
    Longstreth, W. T., Jr.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
    Rolfs, Arndt
    Univ Clin Rostock, Albrecht Kossel Inst, Rostock, Germany.
    Hata, Jun
    Kyushu Univ, Grad Sch Med Sci, Dept Epidemiol & Publ Hlth, Fukuoka, Japan.
    Woo, Daniel
    Univ Cincinnati, Coll Med, Cincinnati, OH USA.
    Rosand, Jonathan
    MGH, Ctr Genom Med, Boston, MA USA;MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
    Pare, Guillaume
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Hopewell, Jemma C.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Saleheen, Danish
    Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
    Stefansson, Kari
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Worrall, Bradford B.
    Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA;Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
    Kittner, Steven J.
    Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA;Baltimore VAMC, Baltimore, MD USA.
    Seshadri, Sudha
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA;Univ Texas Hlth Sci Ctr San Antonio, Glenn Biggs Inst Alzheimers & Neurodegenerat Dis, San Antonio, TX 78229 USA.
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA;Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Markus, Hugh S.
    Univ Cambridge, Div Clin Neurosci, Stroke Res Grp, Cambridge, England.
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.
    Kamatani, Yoichiro
    RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan;Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan.
    Debette, Stephanie
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France.
    Dichgans, Martin
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany;Munich Cluster Syst Neurol SyNergy, Munich, Germany;German Ctr Neurodegenerat Dis DZNE, Munich, Germany.
    Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes2018In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 4, p. 524-537Article in journal (Refereed)
    Abstract [en]

    Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke sub-types. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

  • 319.
    Malmström, H.
    et al.
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, Stockholm, Sweden..
    Wandell, P. E.
    Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Holzmann, M. J.
    Karolinska Univ Hosp, Dept Emergency Med, Huddinge, Sweden.;Karolinska Inst, Dept Internal Med, Solna, Sweden..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Univ Uppsala Hosp, Dept Med Sci, Uppsala, Sweden.;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Jungner, I.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.;CALAB Res, Stockholm, Sweden..
    Hammar, N.
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, Stockholm, Sweden.;AstraZeneca R&D, Med Evidence & Observat Res, Mölndal, Sweden..
    Walldius, G.
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden..
    Carlsson, A. C.
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, Stockholm, Sweden.;Univ Uppsala Hosp, Dept Med Sci, Uppsala, Sweden..
    Low fructosamine and mortality - A long term follow-up of 215,011 non-diabetic subjects in the Swedish AMORIS study2016In: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 26, no 12, p. 1120-1128Article in journal (Refereed)
    Abstract [en]

    Background and aims: Both high and low fasting glucose has been associated with an increased mortality among individuals without diabetes. This J-shaped association has also been shown for HbA1c in relation to all-cause mortality. High fructosamine is associated with increased mortality. In this study we aim to evaluate if low fructosamine is also associated with increased mortality in non-diabetic subjects. Methods and results: We included 215,011 subjects from the AMORIS cohort undergoing occupational health screening or primary care in Stockholm, Sweden. Cause specific mortality was obtained from the Swedish Cause-of-Death Register by record linkage. Hazard ratios for the lowest decile of fructosamine were estimated by Cox regression for all-cause (n = 41,388 deaths) and cause-specific mortality during 25 years of follow-up. We observed gradually increased mortality with lower fructosamine in a large segment of the population. In the lowest decile of fructosamine the sex, age, social class and calendar adjusted hazard ratio was 1.20 (95% CI; 1.18-1.27) compared to deciles 2-9. This increased mortality was attenuated after adjustment for six other biomarkers (HR = 1.11 (95% CI; 1.07-1.15)). Haptoglobin, an indicator of chronic inflammation, made the greatest difference in the point estimate. In sensitivity analyses we found an association between low fructosamine and smoking and adjustment for smoking further attenuated the association between low fructosamine and mortality. Conclusion: Low levels of fructosamine in individuals without diabetes were found to be associated with increased mortality. Smoking and chronic inflammation seem to at least partially explain this association but an independent contribution by low fructosamine cannot be excluded.

  • 320.
    Manning, Alisa
    et al.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA..
    Highland, Heather M.
    Univ Texas MD Anderson Canc Ctr, Human Genet Ctr, Houston, TX 77030 USA.;Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA.;Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA..
    Gasser, Jessica
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Sim, Xueling
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Tukiainen, Taru
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Harvard Med Sch, Dept Genet, Boston, MA USA..
    Fontanillas, Pierre
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;23andMe, Mountain View, CA USA..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Rivas, Manuel A.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Mahajan, Anubha
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Locke, Adam E.
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Cingolani, Pablo
    McGill Univ, Sch Comp Sci, Montreal, PQ, Canada.;McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada..
    Pers, Tune H.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.;Boston Childrens Hosp, Div Endocrinol & Genet, Boston, MA USA.;Boston Childrens Hosp, Div Genom, Boston, MA USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes, Boston, MA USA.;Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark..
    Vinuela, Ana
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.;Univ Geneva, Sch Med, Dept Genet Med & Dev, Geneva, Switzerland.;Univ Geneva, Inst Genet & Genom Geneva, Geneva, Switzerland..
    Brown, Andrew A.
    Wellcome Trust Sanger Inst, Hinxton, England.;Oslo Univ Hosp, Norwegian Ctr Mental Disorders Res, Oslo, Norway.;Oslo Univ Hosp, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict, Oslo, Norway..
    Wu, Ying
    Univ North Carolina Chapel Hill, Dept Genet, Chapel Hill, NC USA..
    Flannick, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA..
    Fuchsberger, Christian
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Gamazon, Eric R.
    Univ Chicago, Dept Med, Sect Genet Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.;Univ Amsterdam, Acad Med Ctr, Amsterdam, Netherlands..
    Gaulton, Kyle J.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA..
    Im, Hae Kyung
    Univ Chicago, Dept Med, Sect Genet Med, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Teslovich, Tanya M.
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Blackwell, Thomas W.
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Burtt, Noel P.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Chen, Yuhui
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Green, Todd
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Hartl, Christopher
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Kang, Hyun Min
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Kumar, Ashish
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Basel, Swiss Trop & Publ Hlth Inst, Chron Dis Epidemiol Unit, Basel, Switzerland..
    Ladenvall, Claes
    Lund Univ, Ctr Diabet, Dept Clin Sci Malmo, Diabet & Endocrinol Unit, Malmo, Sweden..
    Ma, Clement
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Moutsianas, Loukas
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Pearson, Richard D.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Perry, John R. B.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Exeter, Genet Complex Traits, Med Sch, Exeter, Devon, England.;Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England..
    Rayner, N. William
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England..
    Robertson, Neil R.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Scott, Laura J.
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    van de Bunt, Martijn
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Eriksson, Johan G.
    Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.;Univ Helsinki, Unit Gen Practice, Cent Hosp, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Vaasa Cent Hosp, Vaasa, Finland.;Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Tampere, Dept Clin Chem, Fimlab Labs, Sch Med, Tampere, Finland..
    Jula, Antti
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Koskinen, Seppo
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Lehtimaki, Terho
    Palotie, Aarno
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland..
    Jacobs, Suzanne B. R.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Wessel, Jennifer
    Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN USA.;Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA..
    Chu, Audrey Y.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England..
    Goodarzi, Mark O.
    Cedars Sinai Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.;Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA..
    Blancher, Christine
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, High Throughput Genom,Oxford Genom Ctr, Oxford, England..
    Buck, Gemma
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, High Throughput Genom,Oxford Genom Ctr, Oxford, England..
    Buck, David
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, High Throughput Genom,Oxford Genom Ctr, Oxford, England..
    Chines, Peter S.
    NHGRI, NIH, Bethesda, MD 20892 USA..
    Gabriel, Stacey
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Gjesing, Anette P.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Groves, Christopher J.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Hollensted, Mette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Huyghe, Jeroen R.
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Jackson, Anne U.
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Jun, Goo
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Justesen, Johanne Marie
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Murphy, Jacquelyn
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Neville, Matt
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Onofrio, Robert
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Stringham, Heather M.
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Trakalo, Joseph
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, High Throughput Genom,Oxford Genom Ctr, Oxford, England..
    Banks, Eric
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Carey, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Carneiro, Mauricio O.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    DePristo, Mark
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Farjoun, Yossi
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Fennell, Timothy
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Goldstein, Jacqueline I.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA..
    Grant, George
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    de Angelis, Martin Hrabe
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Expt Genet, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Tech Univ Munich, Sch Life Sci Weihenstephan, Inst Expt Genet, Freising Weihenstephan, Germany..
    Maguire, Jared
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Neale, Benjamin M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA..
    Poplin, Ryan
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Purcell, Shaun
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Psychiat, New York, NY 10029 USA..
    Schwarzmayr, Thomas
    German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Shakir, Khalid
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Smith, Joshua D.
    Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA..
    Strom, Tim M.
    German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Neuherberg, Germany..
    Wieland, Thomas
    German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Lindstrom, Jaana
    Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland..
    Brandslund, Ivan
    Univ Southern Denmark, Dept Reg Hlth Res, Odense, Denmark.;Vejle Hosp, Dept Clin Biochem, Vejle, Denmark..
    Christensen, Cramer
    Vejle Hosp, Dept Internal Med & Endocrinol, Vejle, Denmark..
    Surdulescu, Gabriela L.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Lakka, Timo A.
    Univ Eastern FinIand, Inst Biomed, Dept Physiol, Kuopio, Finland.;Kuopio Res Inst Exercise Med, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Doney, Alex S. F.
    Ninewells Hosp & Med Sch, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee, Scotland..
    Nilsson, Peter
    Lund Univ, Fac Med, Dept Clin Sci, Malmo, Sweden..
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England..
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England..
    Varga, Tibor V.
    Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci, Malmo, Sweden.;Lund Univ, Genet & Mol Epidemiol Unit, Malmo, Sweden..
    Franks, Paul W.
    Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci, Malmo, Sweden.;Lund Univ, Genet & Mol Epidemiol Unit, Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Rosengren, Anders H.
    Lund Univ, Ctr Diabet, Dept Clin Sci Malmo, Diabet & Endocrinol Unit, Malmo, Sweden..
    Farook, Vidya S.
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Thameem, Farook
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Puppala, Sobha
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Kumar, Satish
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Lehman, Donna M.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Jenkinson, Christopher P.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.;South Texas Vet Hlth Care Syst, Res & Dev Serv, San Antonio, TX USA..
    Curran, Joanne E.
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Hale, Daniel Esten
    Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA..
    Fowler, Sharon P.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Arya, Rector
    Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA..
    DeFronzo, Ralph A.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Abboud, Hanna E.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hicks, Pamela J.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Palmer, Nicholette D.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA..
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Freedman, Barry I.
    Wake Forest Sch Med, Dept Internal Med, Sect Nephrol, Winston Salem, NC USA..
    Esko, Tonu
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Narisu, Narisu
    NHGRI, NIH, Bethesda, MD 20892 USA..
    Kinnunen, Leena
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Bonnycastle, Lori L.
    NHGRI, NIH, Bethesda, MD 20892 USA..
    Swift, Amy
    NHGRI, NIH, Bethesda, MD 20892 USA..
    Pasko, Dorota
    Univ Exeter, Genet Complex Traits, Med Sch, Exeter, Devon, England..
    Wood, Andrew R.
    Univ Exeter, Genet Complex Traits, Med Sch, Exeter, Devon, England..
    Fadista, Joao
    Lund Univ, Ctr Diabet, Dept Clin Sci Malmo, Diabet & Endocrinol Unit, Malmo, Sweden..
    Pollin, Toni I.
    Univ Maryland, Dept Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA..
    Barzilai, Nir
    Albert Einstein Coll Med, Dept Med, New York, NY USA.;Albert Einstein Coll Med, Dept Genet, New York, NY USA..
    Atzmon, Gil
    Albert Einstein Coll Med, Dept Med, New York, NY USA.;Albert Einstein Coll Med, Dept Genet, New York, NY USA.;Univ Haifa, Fac Nat Sci, Haifa, Israel..
    Glaser, Benjamin
    Hadassah Hebrew Univ, Endocrinol & Metab Serv, Med Ctr, Jerusalem, Israel..
    Thorand, Barbara
    German Ctr Diabet Res DZD, Neuherberg, Germany.;German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Dept Genet Epidemiol, Munich, Germany..
    Peters, Annette
    German Ctr Diabet Res DZD, Neuherberg, Germany.;German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Partner Site Munich Heart Alliance, Herz Kreislauf Forsch DZHK, Deutsch Zentrum, Munich, Germany..
    Roden, Michael
    Heinrich Heine Univ, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;Partner Dusseldorf, German Ctr Diabet Res, Dusseldorf, Germany..
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Dept Genet Epidemiol, Munich, Germany.;Partner Site Munich Heart Alliance, Herz Kreislauf Forsch DZHK, Deutsch Zentrum, Munich, Germany.;Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany..
    Liang, Liming
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Kriebel, Jennifer
    German Ctr Diabet Res DZD, Neuherberg, Germany.;German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.;German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Illig, Thomas
    German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany.;Hannover Med Sch, Inst Human Genet, Hannover, Germany..
    Grallert, Harald
    German Ctr Diabet Res DZD, Neuherberg, Germany.;German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.;German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Gieger, Christian
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Meisinger, Christa
    German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Lannfelt, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Musani, Solomon K.
    Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39216 USA..
    Griswold, Michael
    Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA..
    Taylor, Herman A., Jr.
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Wilson, Gregory, Sr.
    Jackson State Univ, Coll Publ Serv, Jackson, MS USA..
    Correa, Adolfo
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Oksa, Heikki
    Pirkanmaa Hosp Dist, Tampere, Finland..
    Scott, William R.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Afzal, Uzma
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Tan, Sian-Tsung
    Imperial Coll London, Natl Heart & Lung Inst, Cardiovasc Sci, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Loh, Marie
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Univ Oulu, Inst Hlth Sci, Oulu, Finland.;ASTAR, Translat Lab Genet Med, Singapore, Singapore..
    Chambers, John C.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England..
    Sehmi, Jobanpreet
    Imperial Coll London, Natl Heart & Lung Inst, Cardiovasc Sci, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Kooner, Jaspal Singh
    Imperial Coll London, Natl Heart & Lung Inst, Cardiovasc Sci, London, England..
    Lehne, Benjamin
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Cho, Yoon Shin
    Hallym Univ, Dept Biomed Sci, Chunchon, South Korea..
    Lee, Jong-Young
    Minist Hlth & Welf, Seoul, South Korea..
    Han, Bok-Ghee
    Korea Natl Res Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea..
    Karajamaki, Annemari
    Vaasa Hlth Care Ctr, Vaasa, Finland.;Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland..
    Qi, Qibin
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA..
    Qi, Lu
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Huang, Jinyan
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Hu, Frank B.
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Melander, Olle
    Lund Univ, Dept Clin Sci, Hypertens & Cardiovasc Dis, Malmo, Sweden..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, Diabet & Cardiovasc Dis Genet Epidemiol, Malmo, Sweden..
    Below, Jennifer E.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Aguilar, David
    Baylor Coll Med, Cardiovasc Div, Houston, TX 77030 USA..
    Wong, Tien Yin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore..
    Liu, Jianjun
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore..
    Khor, Chiea-Chuen
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Paediat, Singapore, Singapore..
    Chia, Kee Seng
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Lim, Wei Yen
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Cheng, Ching-Yu
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch Singapore, Ctr Quantitat Med, Off Clin Sci, Singapore, Singapore..
    Chan, Edmund
    Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore..
    Tai, E. Shyong
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore.;Duke NUS Grad Med Sch Singapore, Cardiovasc Metab Disorders Program, Singapore, Singapore..
    Aung, Tin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore..
    Linneberg, Allan
    Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Rigshosp, Dept Clin Expt Res, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Isomaa, Bo
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Social Serv & Hlth Care, Pietarsaari, Finland..
    Meitinger, Thomas
    German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Neuherberg, Germany.;Partner Site Munich Heart Alliance, Herz Kreislauf Forsch DZHK, Deutsch Zentrum, Munich, Germany..
    Tuomi, Tiinamaija
    Folkhalsan Res Ctr, Helsinki, Finland.;Helsinki Univ Cent Hosp, Dept Endocrinol, Helsinki, Finland..
    Hakaste, Liisa
    Folkhalsan Res Ctr, Helsinki, Finland..
    Kravic, Jasmina
    Lund Univ, Ctr Diabet, Dept Clin Sci Malmo, Diabet & Endocrinol Unit, Malmo, Sweden..
    Jorgensen, Marit E.
    Steno Diabet Ctr, Gentofte, Denmark..
    Lauritzen, Torsten
    Aarhus Univ, Dept Publ Hlth, Sect Gen Practice, Aarhus, Denmark..
    Deloukas, Panos
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England..
    Stirrups, Kathleen E.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Univ Cambridge, Dept Haematol, Cambridge, England..
    Owen, Katharine R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Farmer, Andrew J.
    Univ Oxford, Dept Primary Care Hlth Sci, Oxford, England..
    Frayling, Timothy M.
    Univ Exeter, Genet Complex Traits, Med Sch, Exeter, Devon, England..
    O'Rahilly, Stephen P.
    Univ Cambridge, Inst Metab Sci, Med Res Labs, Cambridge, England..
    Walker, Mark
    Univ Newcastle, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England..
    Levy, Jonathan C.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Hodgkiss, Dylan
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Hattersley, Andrew T.
    Univ Exeter, Sch Med, Exeter, Devon, England..
    Kuulasmaa, Teemu
    Univ Eastern Finland, Fac Hlth Sci, Inst Clin Med, Internal Med, Kuopio, Finland..
    Stancakova, Alena
    Univ Eastern Finland, Fac Hlth Sci, Inst Clin Med, Internal Med, Kuopio, Finland..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.;Univ Cambridge, Inst Metab Sci, Med Res Labs, Cambridge, England..
    Bharadwaj, Dwaipayan
    CSIR Inst Genom & Integrat Biol, Funct Genom Unit, New Delhi, India..
    Chan, Juliana
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China..
    Chandak, Giriraj R.
    CSIR Ctr Cellular Mol Biol, Hyderabad, Andhra Pradesh, India..
    Daly, Mark J.
    Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA..
    Donnelly, Peter J.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Ebrahim, Shah B.
    Ctr Chron Dis Control, New Delhi, India. Imperial Coll London, MRC, PHE Ctr Environm & Hlth, London, England..
    Elliott, Paul
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Fingerlin, Tasha
    Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA..
    Froguel, Philippe
    CNRS, Inst Biol Lille, Genom & Mol Physiol, Lille, France..
    Hu, Cheng
    Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai Diabet Inst, Dept Endocrinol & Metab, Shanghai, Peoples R China..
    Jia, Weiping
    Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai Diabet Inst, Dept Endocrinol & Metab, Shanghai, Peoples R China..
    Ma, Ronald C. W.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China..
    McVean, Gilean
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Park, Taesung
    Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea.;Seoul Natl Univ, Dept Stat, Seoul, South Korea.;Univ Cambridge, Dept Publ Hlth & Primary Care, Inst Publ Hlth, Cambridge, England..
    Prabhakaran, Dorairaj
    Ctr Chron Dis Control, New Delhi, India. Imperial Coll London, MRC, PHE Ctr Environm & Hlth, London, England..
    Sandhu, Manjinder
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Inst Publ Hlth, Cambridge, England..
    Scott, James
    Imperial Coll London, Natl Heart & Lung Inst, Cardiovasc Sci, London, England..
    Sladek, Rob
    McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ, Dept Med, Div Endocrinol & Metab, Montreal, PQ, Canada..
    Tandon, Nikhil
    All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi, India..
    Teo, Yik Ying
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Singapore, Inst Life Sci, Singapore, Singapore.;Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore, Singapore..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England..
    Watanabe, Richard M.
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Diabet & Obes Res Inst, Los Angeles, CA USA..
    Koistinen, Heikki A.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Dept Med, Helsinki, Finland.;Univ Helsinki, Abdominal Ctr, Endocrinol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Minerva Fdn, Inst Med Res, Helsinki, Finland..
    Kesaniemi, Y. Antero
    Univ Oulu, Inst Clin Med, Fac Med, Oulu, Finland..
    Uusitupa, Matti
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Rauramaa, Rainer
    Fdn Res Hlth Exercise & Nutr, Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Palmer, Colin N. A.
    Ninewells Hosp & Med Sch, Med Res Inst, Pat Macpherson Ctr Pharmacogenet & Pharmacogenom, Dundee, Scotland..
    Prokopenko, Inga
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England..
    Morris, Andrew D.
    Ninewells Hosp & Med Sch, Clin Res Ctr, Div Mol Med, Dundee, Scotland..
    Bergman, Richard N.
    Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA..
    Collins, Francis S.
    NHGRI, NIH, Bethesda, MD 20892 USA..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, Uppsala, Sweden.;Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.;Dasman Diabet Inst, Dasman, Kuwait..
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Groop, Leif
    Lund Univ, Ctr Diabet, Dept Clin Sci Malmo, Diabet & Endocrinol Unit, Malmo, Sweden..
    Jorgensen, Torben
    Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Aalborg Univ, Fac Med, Aalborg, Denmark..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Kuusisto, Johanna
    Univ Eastern Finland, Fac Hlth Sci, Inst Clin Med, Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Abecasis, GonOalo
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Bell, Graeme I.
    Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.;Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA..
    Blangero, John
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Cox, Nancy J.
    Univ Chicago, Dept Med, Sect Genet Med, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Duggirala, Ravindranath
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Seielstad, Mark
    Univ Calif San Francisco, Dept Lab Med, Inst Human Genet, San Francisco, CA 94143 USA.;Blood Syst Res Inst, San Francisco, CA USA..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Ripatti, Samuli
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Univ Helsinki, Hjelt Inst, Helsinki, Finland..
    Hanis, Craig L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Florez, Jose C.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA..
    Mohlke, Karen L.
    Univ North Carolina Chapel Hill, Dept Genet, Chapel Hill, NC USA..
    Meigs, James B.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA..
    Laakso, Markku
    Univ Eastern Finland, Fac Hlth Sci, Inst Clin Med, Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Morris, Andrew P.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Boehnke, Michael
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Altshuler, David
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.;MIT, Dept Biol, Cambridge, MA USA..
    McCarthy, Mark I.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Gloyn, Anna L.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Lindgren, Cecilia M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford, England..
    A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk2017In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 66, no 7, p. 2019-2032Article in journal (Refereed)
    Abstract [en]

    To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.

  • 321.
    Manousaki, Despoina
    et al.
    McGill Univ, Dept Human Genet, Montreal.
    Dudding, Tom
    Univ Bristol, IEU, MRC, Bristol, Avon.
    Haworth, Simon
    Univ Bristol, IEU, MRC, Bristol, Avon.
    Hsu, Yi-Hsiang
    Hebrew SeniorLife, Inst Aging Res, Boston.
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston.
    Medina-Gomez, Carolina
    Erasmus MC, Dept Internal Med, Rotterdam.
    Voortman, Trudy
    Erasmus MC, Dept Epidemiol, Rotterdam.
    van der Velde, Nathalie
    Erasmus MC, Dept Internal Med, Rotterdam.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Robinson-Cohen, Cassiane
    Univ Washington, Div Nephrol, Kidney Res Inst, Seattle.
    Cousminer, Diana
    Childrens Hosp Philadelphia, Div Human Genet, Philadelphia.
    Nethander, Maria
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg.
    Vanderput, Liesbeth
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg.
    Noordam, Raymond
    Leiden Univ, Sect Gerontol & Geriatr, Dept Internal Med, Med Ctr, Leiden.
    Forgetta, Vincenzo
    McGill Univ, Dept Human Genet, Montreal, PQ.
    Greenwood, Celia
    McGill Univ, Dept Human Genet, Montreal, PQ.
    Biggs, Mary Lou
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.;Univ Washington, Dept Biostat, Cardiovasc Hlth Res Unit, Seattle.
    Psaty, Bruce
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.;Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle.
    Rotter, Jerome
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance.
    Zemel, Babette
    Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia.
    Mitchell, Jonathan
    Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia.
    Taylor, Bruce
    Univ Tasmania, Menzies Res Inst Tasmania, Hobart.
    Lorentzon, Matthias
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med, Sahlgrenska Acad, Gothenburg.
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden.;Skane Univ Hosp, Dept Orthopaed, Malmö.
    Jaddoe, Vincent
    Erasmus MC, Generat Study Grp R, Rotterdam.
    Tiemeier, Henning
    Erasmus MC, Generat Study Grp R, Rotterdam.
    Campos-Obando, Natalia
    Erasmus MC, Dept Internal Med, Rotterdam.
    Franco, Oscar
    Erasmus MC, Dept Epidemiol, Rotterdam.
    Uitterlinden, Andre
    Erasmus MC, Dept Internal Med, Rotterdam.
    Broer, Linda
    Erasmus MC, Dept Internal Med, Rotterdam.
    van Schoor, Natasja
    Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam.
    Ham, Annelies
    Erasmus MC, Dept Internal Med, Rotterdam.
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, Rotterdam.
    Karasik, David
    Hebrew SeniorLife, Inst Aging Res, Boston.
    de Mutsert, Renee
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden.
    Rosendaal, Fritz
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden.
    den Heijer, Martin
    Vrije Univ Amsterdam, Dept Endocrinol, Med Ctr, Amsterdam.
    Wang, Thomas
    Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Orwoll, Eric
    Oregon Hlth & Sci Univ, Bone & Mineral Unit, Portland.
    Mook-Kanamori, Dennis O.
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Kestenbaum, Bryan
    Univ Washington, Div Nephrol, Kidney Res Inst, Seattle.
    Ohlsson, Claes
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg.
    Mellstrom, Dan
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg.
    de Groot, Lisette
    Wageningen Univ, Dept Human Nutr, Wageningen.
    Grant, Struan
    Childrens Hosp Philadelphia, Div Human Genet, Philadelphia.
    Kiel, Douglas
    Hebrew SeniorLife, Inst Aging Res, Boston.
    Zillikens, Carola
    Erasmus MC, Dept Internal Med, Rotterdam.
    Rivadeneira, Fernando
    Erasmus MC, Dept Internal Med, Rotterdam.
    Sawcer, Stephen
    Univ Cambridge, Dept Clin Neurosci, Cambridge Biomed Campus, Cambridge.
    Timpson, Nicholas
    Univ Bristol, IEU, MRC, Bristol, Avon.
    Richards, Brent
    McGill Univ, Dept Human Genet, Montreal.
    Low Frequency Coding Variation in CYP2R1 has Large Effects on Vitamin D Level and Risk of Multiple Sclerosis2017In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, no S1, p. S319-S320, article id Meeting Abstract: MO0459Article in journal (Other academic)
  • 322.
    Manousaki, Despoina
    et al.
    McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada..
    Dudding, Tom
    Univ Bristol, Med Res Council, Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Haworth, Simon
    Univ Bristol, Med Res Council, Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Hsu, Yi-Hsiang
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02142 USA..
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Medina-Gomez, Carolina
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Voortman, Trudy
    Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    van der Velde, Nathalie
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Acad Med Ctr, Dept Internal Med, Sect Geriatr, NL-1105 AZ Amsterdam, Netherlands..
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Robinson-Cohen, Cassianne
    Univ Washington, Div Nephrol, Kidney Res Inst, Seattle, WA 98195 USA..
    Cousminer, Diana L.
    Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA..
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Bioinformat Core Facil, S-41390 Gothenburg, Sweden..
    Vandenput, Liesbeth
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden..
    Noordam, Raymond
    Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, NL-2333 ZA Leiden, Netherlands..
    Forgetta, Vincenzo
    McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada..
    Greenwood, Celia M. T.
    McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Oncol, Montreal, PQ H4A 3T2, Canada..
    Biggs, Mary L.
    Univ Washington, Dept Med & Biostat, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA..
    Psaty, Bruce M.
    Univ Washington, Dept Med Epidemiol & Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.;Kaiser Permanente Washington Hlth Res Unit, Seattle, WA 98101 USA..
    Rotter, Jerome I.
    Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA..
    Zemel, Babette S.
    Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA..
    Mitchell, Jonathan A.
    Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA..
    Taylor, Bruce
    Univ Tasmania, Menzies Inst Med Res, Locked Bag 23, Hobart, Tas 7000, Australia..
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Geriatr Med, S-43180 Molndal, Sweden.;Sahlgrens Univ Hosp, Geriatr Med, S-43180 Molndal, Sweden..
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, S-22241 Malmo, Sweden.;Skane Univ Hosp, Dept Orthopaed, S-22241 Malmo, Sweden..
    Jaddoe, Vincent V. W.
    Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Tiemeier, Henning
    Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Child & Adolescent Psychiat Psychol, NL-3015 GE Rotterdam, Netherlands..
    Campos-Obando, Natalia
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Utterlinden, Andre G.
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Broer, Linda
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    van Schoor, Natasja M.
    Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands..
    Ham, Annelies C.
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Radiol & Nucl Med, NL-3015 GE Rotterdam, Netherlands..
    Karasik, David
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA..
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands..
    Rosendaal, Frits R.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands..
    den Heijer, Martin
    Vrije Univ Amsterdam, Med Ctr, Dept Endocrinol, NL-1081 HV Amsterdam, Netherlands..
    Wang, Thomas J.
    Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN 37232 USA..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Orwoll, Eric S.
    Oregon Hlth & Sci Univ, Bone & Mineral Unit, Portland, OR 97239 USA.;Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2333 ZA Leiden, Netherlands..
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Kestenbaum, Bryan
    Univ Washington, Div Nephrol, Kidney Res Inst, Seattle, WA 98195 USA..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden..
    Mellström, Dan K
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Geriatr Med, S-43180 Molndal, Sweden..
    de Groot, Lisette C. P. G. M.
    Wageningen Univ, Div Human Nutr, NL-6708 WE Wageningen, Netherlands..
    Grant, Struan F. A.
    Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Div Endocrinol, Philadelphia, PA 19104 USA..
    Kiel, Douglas P.
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02142 USA.;Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA..
    Zillikens, M. Carola
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Rivadeneira, Fernando
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Sawcer, Stephen
    Univ Cambridge, Dept Clin Neurosci, Box 165,Cambridge Biomed Campus,Hills Rd, Cambridge CB2 0QQ, England..
    Timpson, Nicholas J.
    Univ Bristol, Med Res Council, Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Richards, J. Brent
    McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.;Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.;McGill Univ, Dept Med, Montreal, PQ H3G 1Y6, Canada..
    Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis2017In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 101, no 2, p. 227-238Article in journal (Refereed)
    Abstract [en]

    Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (-0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 x 10(-88)). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78-2.78, p = 1.26 3 10 x(-12)). Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19-1.64, p = 2.63 3 10 x(-5)) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis.

  • 323.
    Marklund, Matti
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Pingel, Ronnie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindroos, Anna Karin
    Natl Food Agency, Uppsala, Sweden;Univ Gothenburg, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Oscarsson, Jan
    AstraZeneca Gothenburg, Molndal, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Interrelationships Between Fatty Acid Composition in Plasma Cholesterol Esters and Phospholipids in Men and Women: A Pooled Analysis2017In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 71, p. 372-372Article in journal (Other academic)
  • 324.
    Marklund, Matti
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Pingel, Ronnie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindroos, Anna Karin
    Natl Food Agcy, Uppsala, Sweden.;Univ Gothenburg, Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. en..
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Oscarsson, Jan
    AstraZeneca R&D, Gothenburg, Sweden..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Fatty Acid Proportions in Plasma Cholesterol Esters and Phospholipids Are Positively Correlated in Various Swedish Populations2017In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 147, no 11, p. 2118-2125Article in journal (Refereed)
    Abstract [en]

    Background: Fatty acid (FA) proportions in cholesterol esters (CEs) and plasma phospholipids are widely used as dietary biomarkers. Information on how proportions in these fractions correlate could have implications for interpretation and use of FA biomarkers in observational and interventional studies. Objective: We investigated correlations between FA proportions in CEs and phospholipids in free-living individuals and assessed how diet-induced alterations of FA proportions correlate between fractions. Methods: Spearman's rank correlation coefficients (rs) between FA proportions (percentage of total FAs) in circulating CEs and phospholipids were calculated separately in 8 individual study populations including Swedish females and males (N = 2052; age range: 11-84 y), and pooled by inverse-variance weighted meta-analysis. In addition, study populations were stratified by age, sex, body mass index (BMI; in kg/m(2)), and diabetes status, and strata-specific rs were pooled by meta-analysis. In 2 randomized trials (N = 79) in which dietary saturated FAs were isocalorically replaced with unsaturated FAs, treatment-wise calculations of rs were conducted between FA changes in CEs and phospholipids. Results: Overall, FA proportions in CEs and phospholipids correlated well and especially strongly for polyunsaturated FAs (PUFAs), with pooled rs (95% CIs) ranging from 0.74 (0.72, 0.76) for a-linolenic acid to 0.92 (0.91, 0.93) for eicosapentaenoic acid. Weak correlations (pooled rs <0.4) were observed only for palmitic acid and stearic acid, with pooled rs (95% CIs): 0.29 (0.24, 0.33) and 0.30 (0.25, 0.34), respectively. Overall, correlations were not affected by age, sex, BMI, or diabetes status. Strong correlations (r(s) >= 0.6) between diet-induced FA changes in CEs and phospholipids were observed for most PUFAs. Conclusions: Proportions of most FAs in CEs and phospholipids ranked individuals similarly, suggesting that FA proportions in these fractions can be used interchangeably in populations of diverse age, sex, body composition, and diabetes status. Caution is advised, however, when comparing results from studies assessing palmitic acid or stearic acid in different lipid fractions.

  • 325.
    Marouli, Eirini
    et al.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England..
    Graff, Mariaelisa
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Medina-Gomez, Carolina
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Lo, Ken Sin
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Wood, Andrew R.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Kjaer, Troels R.
    Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus, Denmark..
    Fine, Rebecca S.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA..
    Lu, Yingchang
    Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA..
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA..
    Highland, Heather M.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.;Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Univ Texas Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Rueger, Sina
    Univ Lausanne Hosp, Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland..
    Thorleifsson, Gudmar
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland..
    Justice, Anne E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Lamparter, David
    Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Lausanne, Dept Comp Biol, CH-1011 Lausanne, Switzerland..
    Stirrups, Kathleen E.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Univ Cambridge, Dept Hematol, Cambridge CB2 0PT, England..
    Turcot, Valerie
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Young, Kristin L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Winkler, Thomas W.
    Univ Regensburg, Dept Genet Epidemiol, D-93051 Regensburg, Germany..
    Esko, Tonu
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Karaderi, Tugce
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Locke, Adam E.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO 63108 USA..
    Masca, Nicholas G. D.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA..
    Mudgal, Poorva
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA..
    Rivas, Manuel A.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Nuffield Dept Clin Med, Oxford OX3 7BN, England..
    Vedantam, Sailaja
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Guo, Xiuqing
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Abecasis, Goncalo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Aben, Katja K.
    Netherland Comprehens Canc Org, NL-3501 DB Utrecht, Netherlands.;Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Adair, Linda S.
    Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA..
    Alam, Dewan S.
    Ctr Control Chron Dis, Dhaka 1212, Bangladesh..
    Albrecht, Eva
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany..
    Allin, Kristine H.
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Allison, Matthew
    Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA..
    Amouyel, Philippe
    INSERM, U1167, F-59019 Lille, France.;Inst Pasteur, U1167, F-59019 Lille, France.;Univ Lille, U1167, RID AGE Risk Factors & Mol Determinants Aging Rel, F-59019 Lille, France..
    Appel, Emil V.
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Arveiler, Dominique
    Univ Strasbourg, Dept Epidemiol & Publ Hlth, F-67085 Strasbourg, France.;Univ Hosp Strasbourg, Dept Publ Hlth, F-67081 Strasbourg, France..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.;ICIN Netherland Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England..
    Auer, Paul L.
    Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA..
    Balkau, Beverley
    INSERM, Ctr Rech Epidemiol & Sante Populat CESP, U1018, Villejuif, France..
    Banas, Bernhard
    Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany..
    Bang, Lia E.
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, DK-2100 Copenhagen, Denmark..
    Benn, Marianne
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Bergmann, Sven
    Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Lausanne, Dept Comp Biol, CH-1011 Lausanne, Switzerland..
    Bielak, Lawrence F.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Blueher, Matthias
    Univ Leipzig, Dept Med, D-04103 Leipzig, Germany..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Epidemiol, D-14558 Nuthetal, Germany..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Boeger, Carsten A.
    Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany..
    Bonnycastle, Lori L.
    NHGRI, Med Genom & Metabol Genet Branch, NIH, Bethesda, MD 20892 USA..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Bots, Michiel L.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC 27157 USA..
    Brandslund, Ivan
    Lillebaelt Hosp, Dept Clin Biochem, DK-7100 Vejle, Denmark.;Univ Southern Denmark, Inst Reg Hlth Res, DK-5000 Odense, Denmark..
    Breen, Gerome
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London SE5 8AF, England.;NIHR Biomed Res Ctr Mental Hlth Maudsley, London SE5 8AF, England..
    Brilliant, Murray H.
    Marshfield Clin Res Fdn, Marshfield, WI 54449 USA..
    Broer, Linda
    Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Burt, Amber A.
    Univ Washington, Dept Med, Seattle, WA 98195 USA..
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England..
    Carey, David J.
    Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA..
    Caulfield, Mark J.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England..
    Chambers, John C.
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Middlesex UB1 3HW, England.;Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.;Univ London Imperial Coll Sci Technol & Med, Healthcare NHS Trust, London W12 0HS, England..
    Chasman, Daniel I.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA..
    Chen, Yii-Der Ida
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Chowdhury, Rajiv
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England..
    Christensen, Cramer
    Lillebaelt Hosp, Dept Med, DK-7100 Vejle, Denmark..
    Chu, Audrey Y.
    Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA.;NHLBI, Framingham Heart Study, Framingham, MA 01702 USA..
    Cocca, Massimiliano
    Univ Trieste, Dept Med Surg & Hlth Sci, I-34100 Trieste, Italy..
    Collins, Francis S.
    NHGRI, Med Genom & Metabol Genet Branch, NIH, Bethesda, MD 20892 USA..
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England..
    Corley, Janie
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Galbany, Jordi Corominas
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands..
    Cox, Amanda J.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA.;Griffith Univ, Menzies Hlth Inst Queensland, Southport, Qld, Australia..
    Cuellar-Partida, Gabriel
    Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia.;QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England.;Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England.;Univ Cambridge, Dept Med, Cambridge Escellence, British Heart Fdn, Cambridge CB2 0QQ, England..
    Davies, Gail
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    de Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Ctr Mol Med, Dept Genet, NL-3584 CX Utrecht, Netherlands..
    de Borst, Gert J.
    Univ Med Ctr Utrecht, Dept Vasc Surg, Div Surg Specialties, NL-3584 CX Utrecht, Netherlands..
    de Denus, Simon
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada..
    de Groot, Mark C. H.
    Univ Med Ctr Utrecht, Div Lab & Pharm, Dept Clin Chem & Haematol, NL-3508 GA Utrecht, Netherlands.;Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht Inst Pharmaceut Sci, NL-3508 TB Utrecht, Netherlands..
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Dedoussis, George
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens 17671, Greece..
    Demerath, Ellen W.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA..
    den Hollander, Anneke I.
    Radbound Univ Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands..
    Dennis, Joe G.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Di Angelantonio, Emanuele
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England..
    Drenos, Fotios
    UCL, Inst Cardiovasc Sci, London WC1E 6JF, England.;Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Du, Mengmeng
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.;Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10017 USA..
    Dunning, Alison M.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.;Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland..
    Easton, Douglas F.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.;Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Ebeling, Tapani
    Oulu Univ Hosp, Dept Med, Oulu 90029, Finland.;Univ Oulu, Res Unit Internal Med, FI-90014 Oulu, Finland..
    Edwards, Todd L.
    Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Med,Div Epidemiol, Nashville, TN 37203 USA..
    Ellinor, Patrick T.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA..
    Elliott, Paul
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Evangelou, Evangelos
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece..
    Farmaki, Aliki-Eleni
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens 17671, Greece..
    Faul, Jessica D.
    Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48104 USA..
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA..
    Feng, Shuang
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Ferrannini, Ele
    CNR Inst Clin Physiol, Pisa, Italy.;Univ Pisa, Dept Clin & Expt Med, Pisa, Italy..
    Ferrario, Marco M.
    Univ Insubria, Dept Clin & Expt Med, Res Ctr Epidemiol & Prevent Med, I-21100 Varese, Italy..
    Ferrieres, Jean
    Toulouse Univ, Sch Med, F-31059 Toulouse, France..
    Florez, Jose C.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA..
    Ford, Ian
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Franks, Paul W.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Umea Univ, Med Unit, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Frikke-Schmidt, Ruth
    Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark..
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Gan, Wei
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Gandin, Ilaria
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy..
    Gasparini, Paolo
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy.;Sidra Med & Res Ctr, Div Expt Genet, Doha 26999, Qatar..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Giri, Ayush
    Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Med,Div Epidemiol, Nashville, TN 37203 USA..
    Girotto, Giorgia
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy.;Sidra Med & Res Ctr, Div Expt Genet, Doha 26999, Qatar..
    Gordon, Scott D.
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Gordon-Larsen, Penny
    Univ N Carolina, Caroline Populat Ctr, Chapel Hill, NC 27514 USA.;Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27514 USA..
    Gorski, Mathias
    Univ Regensburg, Dept Genet Epidemiol, D-93051 Regensburg, Germany.;Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany.;Univ Leipzig, IFB Adipos Dis, D-04103 Leipzig, Germany..
    Grarup, Niels
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Grove, Megan L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Gudnason, Vilmundur
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;Icelandic Heart Assoc, IS-201 Kopavogur, Iceland..
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Hansen, Torben
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Harris, Kathleen Mullan
    Univ N Carolina, Caroline Populat Ctr, Chapel Hill, NC 27514 USA.;Univ N Carolina, Dept Sociol, Chapel Hill, NC 27514 USA..
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA..
    Hattersley, Andrew T.
    Univ Exeter, Univ Exeter Med Sch, Exeter EX2 5DW, Devon, England..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRCHGU, Edinburgh EH4 2XU, Midlothian, Scotland..
    He, Liang
    Duke Univ, Social Sci Res Inst, Biodemog Aging Res Unit, Durham, NC 27708 USA.;Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland..
    Heid, Iris M.
    Univ Regensburg, Dept Genet Epidemiol, D-93051 Regensburg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany..
    Heikkila, Kauko
    Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland..
    Helgeland, Oyvind
    Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway.;Univ Bergen, Dept Clin Sci, KG Jebson Ctr Diabet Res, N-5020 Bergen, Norway..
    Hernesniemi, Jussi
    Tampere Univ Hosp, Dept Cardiol, Ctr Heart, FI-33521 Tampere, Finland.;Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Hewitt, Alex W.
    Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.;Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Vis Sci, Perth, WA 6009, Australia.;Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas 7000, Australia..
    Hocking, Lynne J.
    Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh EH4 2XU, Midlothian, Scotland.;Univ Aberdeen, Div Appl Med, Musculoskeletal Res Programme, Aberdeen AB25 2ZD, Scotland..
    Hollensted, Mette
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Holmen, Oddgeir L.
    Norwegian Univ Sci & Technol, NTNU, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7600 Trondheim, Norway..
    Hovingh, G. Kees
    AMC, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands..
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England..
    Hoyng, Carel B.
    Radbound Univ Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands..
    Huang, Paul L.
    Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Hveem, Kristian
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway..
    Ikram, M. Arfan
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Neurol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Radiol, NL-3015 GE Rotterdam, Netherlands..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Jansson, Jan-Hakan
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden.;Res Unit Skelleftea, SE-93141 Skelleftea, Sweden..
    Jarvik, Gail P.
    Univ Washington, Dept Med, Seattle, WA 98195 USA.;Univ Washington, Dept Genom Sci, Seattle, WA 98195 USA..
    Jensen, Gorm B.
    Frederiksberg Univ Hosp, Copenhagen City Heart Study, DK-2000 Frederiksberg, Denmark..
    Jhun, Min A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Jia, Yucheng
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Jiang, Xuejuan
    Univ Calif Los Angeles, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.;Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA 90089 USA..
    Johansson, Stefan
    Univ Bergen, Dept Clin Sci, KG Jebson Ctr Diabet Res, N-5020 Bergen, Norway.;Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway..
    Jorgensen, Marit E.
    Univ Southern Denmark, Natl Inst Publ Hlth, DK-1353 Copenhagen, Denmark.;Steno Diabet Ctr, DK-2820 Gentofte, Denmark..
    Jorgensen, Torben
    Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Aalborg Hosp, DK-9000 Aalborg, Denmark.;Capital Reg Denmark, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark..
    Jousilahti, Pekka
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Jukema, J. Wouter
    Leiden Univ Med Ctr, Dept Cardiol, NL-2333 Leiden, Netherlands.;Interuniv Cardiol Inst Netherlands, NL-2333 Utrecht, Netherlands..
    Kahali, Bratati
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA..
    Kahn, Rene S.
    Ctr Med Univ Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3584 CG Utrecht, Netherlands..
    Kahonen, Mika
    Univ Tampere, Sch Med, Dept Clin Physiol, Tampere 33014, Finland..
    Kamstrup, Pia R.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark..
    Kanoni, Stavroula
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England..
    Kaprio, Jaakko
    Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland.;Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Karaleftheri, Maria
    Echinos Med Ctr, Echinos, Greece..
    Kardia, Sharon L. R.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    Kee, Frank
    Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth Res, Belfast BT12 6BJ, Antrim, North Ireland..
    Keeman, Renske
    Netherlands Canc Inst, Antoni van Leewenhoek Hosp, NL-1066 CX Amsterdam, Netherlands..
    Kiemeney, Lambertus A.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Kitajima, Hidetoshi
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Kluivers, Kirsten B.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Kocher, Thomas
    Univ Med Greifswald, Dept Restorat Dent Periodontol & Endodontol, D-17475 Greifswald, Germany..
    Komulainen, Pirjo
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland..
    Kontto, Jukka
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Kooner, Jaspal S.
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Middlesex UB1 3HW, England.;Univ London Imperial Coll Sci Technol & Med, Healthcare NHS Trust, London W12 0HS, England.;Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Hammersmith Hosp Campus, London W12 0NN, England..
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Kovacs, Peter
    Univ Leipzig, IFB Adipos Dis, D-04103 Leipzig, Germany..
    Kriebel, Jennifer
    German Ctr Diabet Res, D-85764 Munich, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany..
    Kuivaniemi, Helena
    Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Dept Psychiat, ZA-7505 Tygerberg, Western Cape, South Africa.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Div Mol Biol & Human Genet, ZA-7505 Tygerberg, Western Cape, South Africa..
    Kury, Sebastien
    CHU Nantes, Serv Genet Med, F-44093 Nantes, France..
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, SF-70210 Kuopio, Finland..
    La Bianca, Martina
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy..
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, SF-70210 Kuopio, Finland..
    Lakka, Timo A.
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland.;Univ Eastern Finland, Inst Biomed & Physiol, Kuopio 70210, Finland..
    Lange, Ethan M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Lange, Leslie A.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Langefeld, Carl D.
    Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC 27157 USA..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Larson, Eric B.
    Univ Washington, Dept Med, Seattle, WA 98195 USA.;Grp Hlth Res Inst, Seattle, WA 98101 USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA..
    Lee, I-Te
    Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrinol & Metab, Taichung 407, Taiwan.;Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan.;Chung Shan Med Univ, Sch Med, Taichung 402, Taiwan..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Lewis, Cora E.
    Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL 35205 USA..
    Li, Huaixing
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Li, Jin
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Palo Alto, CA 94305 USA..
    Li-Gao, Ruifang
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands..
    Lin, Honghuang
    Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA..
    Lin, Li-An
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Lin, Xu
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindstrom, Jaana
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Linneberg, Allan
    Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Capital Reg Denmark, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark.;Rigshosp, Dept Expt Med, DK-2200 Copenhagen, Denmark..
    Liu, Yeheng
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Liu, Yongmei
    Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA..
    Lophatananon, Artitaya
    Warsaw Acad Med & Hosp, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Lubitz, Steven A.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Mackey, David A.
    Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Vis Sci, Perth, WA 6009, Australia..
    Madden, Pamela A. F.
    Washington Univ, Dept Psychiat, St Louis, MO 63110 USA..
    Manning, Alisa K.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland..
    Mannisto, Satu
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Marenne, Gaelle
    Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Marten, Jonathan
    Univ Edinburgh, Inst Genet & Mol Med, MRCHGU, Edinburgh EH4 2XU, Midlothian, Scotland..
    Martin, Nicholas G.
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Mazul, Angela L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Meidtner, Karina
    German Ctr Diabet Res, D-85764 Munich, Germany.;German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, D-14558 Nuthetal, Germany..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Mitchell, Paul
    Univ Sydney, Ctr Vis Res, Westmead Millennium Inst Med Res, Sydney, NSW 2022, Australia.;Univ Sydney, Dept Ophthalmol, Sydney, NSW 2022, Australia..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2300 RC Leiden, Netherlands..
    Morgan, Anna
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy..
    Morris, Andrew D.
    Univ Edinburgh, Ctr Global Hlth Res, Ushar Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.;Univ Munich, Dept Med 1, D-81377 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany..
    Munroe, Patricia B.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England..
    Nalls, Mike A.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Nauck, Matthias
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.;Univ Med Greifswald, Inst Clin Chem, D-17475 Greifswald, Germany.;Univ Med Greifswald, Lab Med, D-17475 Greifswald, Germany..
    Nelson, Christopher P.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Neville, Matt
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    Nielsen, Sune F.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Nikus, Kjell
    Univ Tampere, Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere 33521, Finland.;Univ Tampere, Sch Med, Tampere 33521, Finland..
    Njolstad, Pal R.
    Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway.;Univ Bergen, Dept Clin Sci, KG Jebson Ctr Diabet Res, N-5020 Bergen, Norway..
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Ntalla, Ioanna
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England..
    O'Connel, Jeffrey R.
    Univ Maryland, Sch Med, Dept Med, Program Personalized Med, Baltimore, MD 21201 USA..
    Oksa, Heikki
    Tampere Univ Hosp, Dept Med, Tampere 33521, Finland..
    Loohuis, Loes M. Olde
    Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA..
    Ophoff, Roel A.
    Ctr Med Univ Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3584 CG Utrecht, Netherlands.;Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA..
    Owen, Katharine R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    Packard, Chris J.
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Padmanabhan, Sandosh
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Palmer, Colin N. A.
    Ninewells Hosp & Med Sch, Med Res Inst, Pat Macpherson Ctr Pharmacogenet & Pharmacogenom, Dundee DD1 9SY, Scotland..
    Pasterkamp, Gerard
    Univ Med Ctr Utrecht, Div Labs & Pharm, Lab Clin Chem & Hematol, NL-3584 CX Utrecht, Netherlands..
    Patel, Aniruddh P.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Pattie, Alison
    Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Pedersen, Oluf
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Peissig, Peggy L.
    Marshfield Clin Res Fdn, Marshfield, WI 54449 USA..
    Peloso, Gina M.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA..
    Pennell, Craig E.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia..
    Perola, Markus
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland.;Univ Helsinki, Inst Mol Med FIMM, FI-00014 Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, FI-00014 Helsinki, Finland.;Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Perry, James A.
    Univ Maryland, Sch Med, Dept Med, Program Personalized Med, Baltimore, MD 21201 USA..
    Perry, John R. B.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Person, Thomas N.
    Marshfield Clin Res Fdn, Marshfield, WI 54449 USA..
    Pirie, Ailith
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Polasek, Ozren
    Univ Edinburgh, Ctr Global Hlth Res, Ushar Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.;Univ Split, Sch Med, Split 21000, Croatia..
    Posthuma, Danielle
    Vrije Univ Amsterdam, Dept Complex Trait Genet, Ctr Neurogenom & Cognit Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Neurosci Campus Amsterdam, NL-1081 HV Amsterdam, Netherlands..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland..
    Rasheed, Asif
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland..
    Reilly, Dermot F.
    MRL Merck & Co Inc, Genet & Pharmacogenom, Boston, MA 02115 USA..
    Reiner, Alex P.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Renstrom, Frida
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden.;Umea Univ, Dept Biobank Res, SE-90187 Umea, Sweden..
    Ridker, Paul M.
    Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA.;Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA..
    Rioux, John D.
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3T 1J4, Canada..
    Robertson, Neil
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England..
    Robino, Antonietta
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden.;Umea Univ, Unit Family Med, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden..
    Rudan, Igor
    Univ Edinburgh, Ctr Global Hlth Res, Ushar Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Ruth, Katherine S.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Saleheen, Danish
    Ctr Noncommunicable Dis, Karachi, Pakistan.;Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Samani, Nilesh J.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Sandow, Kevin
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Sapkota, Yadav
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Sattar, Naveed
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Schmidt, Marjanka K.
    Netherlands Canc Inst, Antoni van Leewenhoek Hosp, NL-1066 CX Amsterdam, Netherlands..
    Schreiner, Pamela J.
    Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA..
    Schulze, Matthias B.
    German Ctr Diabet Res, D-85764 Munich, Germany.;German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, D-14558 Nuthetal, Germany..
    Scott, Robert A.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Segura-Lepe, Marcelo P.
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Shah, Svati
    Duke Univ, Durham, NC 27703 USA..
    Sim, Xueling
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Sivapalaratnam, Suthesh
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Univ Cambridge, Dept Haematol, Cambridge CB2 0PT, England.;AMC, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Smith, Albert Vernon
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;Icelandic Heart Assoc, IS-201 Kopavogur, Iceland..
    Smith, Jennifer A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Southam, Lorraine
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Speliotes, Elizabeth K.
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Steinthorsdottir, Valgerdur
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland..
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Stumvoll, Michael
    Univ Leipzig, IFB Adipos Dis, D-04103 Leipzig, Germany.;Univ Leipzig, Dept Med, D-04103 Leipzig, Germany..
    Surendran, Praveen
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England..
    't Hart, Leen M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands.;Leiden Univ, Med Ctr, Dept Mol & Cell Biol, NL-2333 ZC Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2333 ZC Leiden, Netherlands..
    Tansey, Katherine E.
    Cardiff Univ, Coll Biomed & Life Sci, Cardiff CF14 4EP, S Glam, Wales.;Univ Bristol, Dept Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Tardif, Jean-Claude
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3T 1J4, Canada..
    Taylor, Kent D.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Teumer, Alexander
    Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.;Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany..
    Thompson, Deborah J.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Thorsteinsdottir, Unnur
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Thuesen, Betina H.
    Capital Reg Denmark, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark..
    Toenjes, Anke
    Univ Leipzig, Dept Womens & Child Hlth, Ctr Pediat Res, D-04103 Leipzig, Germany..
    Tromp, Gerard
    Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Div Human Genet & Mol Biol, ZA-7505 Tygerberg, Western Cape, South Africa..
    Trompet, Stella
    Leiden Univ Med Ctr, Dept Cardiol, NL-2333 Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2333 Leiden, Netherlands..
    Tsafantakis, Emmanouil
    Anogia Med Ctr, Anogia, Greece..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland.;Danube Univ Krems, Ctr Vasc Prevent, A-3500 Krems, Austria.;Dasman Diabet Inst, Dasman 15462, Kuwait.;King Abdulaziz Univ, Diabet Res Grp, Jeddah 21589, Saudi Arabia..
    Tybjaerg-Hansen, Anne
    Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark..
    Tyrer, Jonathan P.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Uher, Rudolf
    Dalhousie Univ, Dept Psychiat, Halifax, NS B3H 4R2, Canada..
    Uitterlinden, Andre G.
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Ulivi, Sheila
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy..
    van der Laan, Sander W.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, NL-3584 CX Utrecht, Netherlands..
    Van Der Leij, Andries R.
    Univ Amsterdam, Dept Brain & Cognit, NL-1018 WS Amsterdam, Netherlands..
    van Duijn, Cornelia M.
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    van Schoor, Natasja M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands..
    van Setten, Jessica
    Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands..
    Varbo, Anette
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Varga, Tibor V.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
    Varma, Rohit
    Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA 90089 USA..
    Edwards, Digna R. Velez
    Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Obstet & Gynecol, Nashville, TN 37203 USA..
    Vermeulen, Sita H.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Vestergaard, Henrik
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Vitart, Veronique
    Univ Edinburgh, Inst Genet & Mol Med, MRCHGU, Edinburgh EH4 2XU, Midlothian, Scotland..
    Vogt, Thomas F.
    MRL Merck Co Inc, Cardiometab Dis, Kenilworth, NJ 07033 USA..
    Vozzi, Diego
    Sidra Med & Res Ctr, Div Expt Genet, Doha 26999, Qatar..
    Walker, Mark
    Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England..
    Wang, Feijie
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Wang, Carol A.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia..
    Wang, Shuai
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Wang, Yiqin
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Warren, Helen R.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England..
    Wessel, Jennifer
    Indiana Univ, Fairbanks Sch Publ Hlth, Diabet Translat Res Ctr, Dept Epidemiol & Med, Indianapolis, IN 46202 USA.;Indiana Univ, Sch Med, Indianapolis, IN 46202 USA..
    Willems, Sara M.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Witte, Daniel R.
    Danish Diabet Acad, DK-5000 Odense, Denmark.;Aarhus Univ, Dept Publ Hlth, DK-8000 Aarhus, Denmark..
    Woods, Michael O.
    Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF A1B 3V6, Canada..
    Wu, Ying
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Yaghootkar, Hanieh
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Yao, Jie
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Yao, Pang
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Yerges-Armstrong, Laura M.
    Univ Maryland, Sch Med, Dept Med, Program Personalized Med, Baltimore, MD 21201 USA.;GlaxoSmithKlein, King Of Prussia, PA 19406 USA..
    Young, Robin
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Zhan, Xiaowei
    Univ Texas Southwestern Med Ctr Dallas, Quantitat Biomed Res Ctr, Ctr Genet Host Def, Dept Clin Sci, Dallas, TX 75390 USA..
    Zhang, Weihua
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Middlesex UB1 3HW, England.;Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Zhao, Wei
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.;Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA..
    Zheng, He
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Zhou, Wei
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Rotter, Jerome I.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Kathiresan, Sekar
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    Willer, Cristen J.
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Stefansson, Kari
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA..
    Liu, Dajiang J.
    Penn State Univ, Coll Med, Inst Personalized Med, Dept Publ Hlth Sci, Hershey, PA 17033 USA..
    North, Kari E.
    Dept Epidemiol, Chapel Hill, NC 27514 USA.;Carolina Ctr Genome Sci, Chapel Hill, NC 27514 USA..
    Heard-Costa, Nancy L.
    NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.;Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA..
    Pers, Tune H.
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark.;Statens Serum Inst, Dept Epidemiol Res, DK-2200 Copenhagen, Denmark..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford OX3 7BN, England..
    Oxvig, Claus
    Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus, Denmark..
    Kutalik, Zoltan
    Univ Lausanne Hosp, Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland..
    Rivadeneira, Fernando
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10069 USA..
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Hirschhorn, Joel N.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Harvard Med Sch, Dept Pediat & Genet, Boston, MA 02115 USA..
    Deloukas, Panos
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia..
    Lettre, Guillaume
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3T 1J4, Canada..
    Rare and low-frequency coding variants alter human adult height2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 542, no 7640, p. 186-190Article in journal (Refereed)
    Abstract [en]

    Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

  • 326.
    Masiha, Said
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Inflammatory markers are associated with left ventricular hypertrophy and diastolic dysfunction in a population-based sample of elderly men and women2013In: Journal of Human Hypertension, ISSN 0950-9240, E-ISSN 1476-5527, Vol. 27, no 1, p. 13-7Article in journal (Refereed)
    Abstract [en]

    Markers of inflammation have previously been related to left ventricular (LV) hypertrophy (LVH) in uremic and hypertensive patients. The present study investigated inflammatory markers in relation to LV geometry and diastolic function in a population of elderly persons. In the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (1016 men and women 70 years of age), echocardiograms to determine relative wall thickness (RWT), LV mass index (LVMI) and the E/A-ratio were obtained. Based on RWT and LVMI, four geometric subgroups were defined; normal, concentric remodeling, eccentric and concentric LVH. In all, 10 circulating inflammatory markers were measured. Higher levels of high sensitive C-reactive protein (hsCRP) and E-selectin were seen in the three abnormal geometry groups than in the normal group adjusting for gender, body mass index, systolic and diastolic blood pressure and use of antihypertensive medication. Higher level of inter-cellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1) and P-selectin were only seen in concentric LVH. Levels of tumor necrosis factor-alpha, interleukin-6, l-selectin, monocyte chemotactic protein-1 and leukocyte count did not differ between the LV groups. l-selectin and hsCRP were related to the E/A-ratio. The adhesion molecules; E-selectin, ICAM-1, VCAM-1, P-selectin and hsCRP were elevated in elderly persons with abnormal LV geometry, especially in concentric LVH, after adjusting for hypertension and obesity. l-selectin and hsCRP were related to LV diastolic function. Further studies are motivated to investigate a pathogenetic role of inflammation for abnormal LV geometry and function.

  • 327. Matsushita, Kunihiro
    et al.
    Coresh, Josef
    Sang, Yingying
    Chalmers, John
    Fox, Caroline
    Guallar, Eliseo
    Jafar, Tazeen
    Jassal, Simerjot K.
    Landman, Gijs W. D.
    Muntner, Paul
    Roderick, Paul
    Sairenchi, Toshimi
    Schoettker, Ben
    Shankar, Anoop
    Shlipak, Michael
    Tonelli, Marcello
    Townend, Jonathan
    van Zuilen, Arjan
    Yamagishi, Kazumasa
    Yamashita, Kentaro
    Gansevoort, Ron
    Sarnak, Mark
    Warnock, David G.
    Woodward, Mark
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data2015In: LANCET DIABETES & ENDOCRINOLOGY, ISSN 2213-8587, Vol. 3, no 7, p. 514-525Article in journal (Refereed)
    Abstract [en]

    Background The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach. Methods We meta-analysed individual-level data for 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4.2-19.0 years) included in the Chronic Kidney Disease Prognosis Consortium. We assessed C statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in a 5 year timeframe, contrasting prediction models for traditional risk factors with and without creatinine-based eGFR, albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria), or both. Findings The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR, and more evident for cardiovascular mortality (C statistic difference 0.0139 [95% CI 0.0105- 0.0174] for ACR and 0.0065 [0.0042-0.0088] for eGFR) and heart failure (0.0196 [0.0108-0.0284] and 0.0109 [0.0059-0.0159]) than for coronary disease (0.0048 [0.0029-0.0067] and 0.0036 [0.0019-0.0054]) and stroke (0.0105 [0.0058-0.0151]and 0.0036 [0.0004-0.0069]). Dipstick proteinuria showed smaller improvement than ACR. The discrimination improvement with eGFR or ACR was especially evident in individuals with diabetes or hypertension, but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these disorders. In individuals with chronic kidney disease, the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the C statistic for cardiovascular mortality fell by 0.0227 (0.0158-0.0296) after omission of eGFR and ACR compared with less than 0.007 for any single modifiable traditional predictor. Interpretation Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when these measures are already assessed for clinical purpose or if cardiovascular mortality and heart failure are outcomes of interest. ACR could have particularly broad implications for cardiovascular prediction. In populations with chronic kidney disease, the simultaneous assessment of eGFR and ACR could facilitate improved classification of cardiovascular risk, supporting current guidelines for chronic kidney disease. Our results lend some support to also incorporating eGFR and ACR into assessments of cardiovascular risk in the general population.

  • 328.
    Mendelson, Michael M.
    et al.
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;Boston Univ, Sch Med, Boston, MA 02118 USA.;Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Marioni, Riccardo E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Joehanes, Roby
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.;Harvard Med Sch, Hebrew SeniorLife, Boston, MA USA..
    Liu, Chunyu
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.;Boston Univ, Dept Biostat, Boston, MA USA..
    Hedman, Åsa K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Aslibekyan, Stella
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA..
    Demerath, Ellen W.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Guan, Weihua
    Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA..
    Zhi, Degui
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA..
    Yao, Chen
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Huan, Tianxiao
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Willinger, Christine
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Chen, Brian
    NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Courchesne, Paul
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Multhaup, Michael
    Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA..
    Lrvin, Marguerite R.
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA..
    Cohain, Ariella
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA..
    Schadt, Eric E.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA..
    Grove, Megan L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Bressler, Jan
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    North, Kari
    Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Shah, Sonia
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    McRae, Allan F.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Harris, Sarah E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH8 9YL, Midlothian, Scotland..
    Gibson, Jude
    Univ Edinburgh, Western Gen Hosp, Wellcome Trust Clin Res Facil, Edinburgh EH8 9YL, Midlothian, Scotland..
    Redmond, Paul
    Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland..
    Coriey, Janie
    Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland..
    Murphy, Lee
    Univ Edinburgh, Western Gen Hosp, Wellcome Trust Clin Res Facil, Edinburgh EH8 9YL, Midlothian, Scotland..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9YL, Midlothian, Scotland..
    Kleinbrink, Erica
    Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.;Wayne State Univ, Dept Neurol, Detroit, MI USA..
    Lipovich, Leonard
    Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.;Wayne State Univ, Dept Neurol, Detroit, MI USA..
    Visscher, Peter M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Wray, Naomi R.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Krauss, Ronald M.
    Childrens Hosp Oakland Res Inst, Oakland, CA USA..
    Fallin, Daniele
    Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA..
    Feinberg, Andrew
    Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA..
    Absher, Devin M.
    HudsonAlpha Inst Biotechnol, Huntsville, AL USA..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Univ Texas Houston, Brown Fdn Inst Mol Med, Houston, TX USA..
    Pankow, James S.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Fox, Caroline
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Arnett, Donna K.
    Univ Kentucky, Coll Publ Hlth, Lexington, KY USA..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Liang, Liming
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA..
    Levy, Daniel
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Deary, Lan J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland..
    Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach2017In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, no 1, article id e1002215Article in journal (Refereed)
    Abstract [en]

    Background The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. Methods and Findings We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination. Conclusions We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases.

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  • 329.
    Mobacke, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Dunder, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Circulating levels of perfluoroalkyl substances and left ventricular geometry of the heart in the elderly.2018In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 115, p. 295-300Article in journal (Refereed)
    Abstract [en]

    AIMS: Some persistent organic pollutants (POPs) such as hexachlorobenzene (HCB) and some polychlorinated biphenyls (PCBs) have been shown to interfere with myocardial function and geometry. We therefore investigated if also another group of POPs: per- and polyfluoroalkyl substances (PFASs) were associated with alterations in left ventricular geometry.

    METHODS: 801 subjects aged 70 years were investigated in a cross-sectional study within the scope of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eight PFASs were detected in >75% of participants´ plasma by ultra-performance liquid chromatograph/tandem mass spectrometry. Left ventricular geometry was determined by echocardiography. Multivariable linear regression was used to investigate the associations between PFASs and left ventricular geometry of the heart after exclusion of subjects with previous myocardial infarction (n = 72).

    RESULTS: When adjusting for multiple comparisons, none of the eight PFASs evaluated were significantly related to left ventricular mass. However, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were related to relative wall thickness (RWT) in a negative fashion (p < 0.0021). Besides being inversely related to RWT, PFNA was also positively related to left ventricular end-diastolic volume (LVEDD) (p < 0.0021). These analyses were adjusted for traditional cardiovascular risk factors.

    CONCLUSION: In this cross-sectional study, several of the PFASs evaluated, especially PFNA, were related to myocardial geometry: a reduction in relative wall thickness and an increase in left ventricular diameter following adjustment for traditional cardiovascular risk factors, suggesting a role for PFASs in cardiac remodeling.

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  • 330. Morris, Andrew P.
    et al.
    Voight, Benjamin F.
    Teslovich, Tanya M.
    Ferreira, Teresa
    Segre, Ayellet V.
    Steinthorsdottir, Valgerdur
    Strawbridge, Rona J.
    Khan, Hassan
    Grallert, Harald
    Mahajan, Anubha
    Prokopenko, Inga
    Kang, Hyun Min
    Dina, Christian
    Esko, Tonu
    Fraser, Ross M.
    Kanoni, Stavroula
    Kumar, Ashish
    Lagou, Vasiliki
    Langenberg, Claudia
    Luan, Jian'an
    Lindgren, Cecilia M.
    Mueller-Nurasyid, Martina
    Pechlivanis, Sonali
    Rayner, N. William
    Scott, Laura J.
    Wiltshire, Steven
    Yengo, Loic
    Kinnunen, Leena
    Rossin, Elizabeth J.
    Raychaudhuri, Soumya
    Johnson, Andrew D.
    Dimas, Antigone S.
    Loos, Ruth J. F.
    Vedantam, Sailaja
    Chen, Han
    Florez, Jose C.
    Fox, Caroline
    Liu, Ching-Ti
    Rybin, Denis
    Couper, David J.
    Kao, Wen Hong L.
    Li, Man
    Cornelis, Marilyn C.
    Kraft, Peter
    Sun, Qi
    van Dam, Rob M.
    Stringham, Heather M.
    Chines, Peter S.
    Fischer, Krista
    Fontanillas, Pierre
    Holmen, Oddgeir L.
    Hunt, Sarah E.
    Jackson, Anne U.
    Kong, Augustine
    Lawrence, Robert
    Meyer, Julia
    Perry, John R. B.
    Platou, Carl G. P.
    Potter, Simon
    Rehnberg, Emil
    Robertson, Neil
    Sivapalaratnam, Suthesh
    Stancakova, Alena
    Stirrups, Kathleen
    Thorleifsson, Gudmar
    Tikkanen, Emmi
    Wood, Andrew R.
    Almgren, Peter
    Atalay, Mustafa
    Benediktsson, Rafn
    Bonnycastle, Lori L.
    Burtt, Noel
    Carey, Jason
    Charpentier, Guillaume
    Crenshaw, Andrew T.
    Doney, Alex S. F.
    Dorkhan, Mozhgan
    Edkins, Sarah
    Emilsson, Valur
    Eury, Elodie
    Forsen, Tom
    Gertow, Karl
    Gigante, Bruna
    Grant, George B.
    Groves, Christopher J.
    Guiducci, Candace
    Herder, Christian
    Hreidarsson, Astradur B.
    Hui, Jennie
    James, Alan
    Jonsson, Anna
    Rathmann, Wolfgang
    Klopp, Norman
    Kravic, Jasmina
    Krjutskov, Kaarel
    Langford, Cordelia
    Leander, Karin
    Lindholm, Eero
    Lobbens, Stephane
    Mannisto, Satu
    Mirza, Ghazala
    Muehleisen, Thomas W.
    Musk, Bill
    Parkin, Melissa
    Rallidis, Loukianos
    Saramies, Jouko
    Sennblad, Bengt
    Shah, Sonia
    Sigurdsson, Gunnar
    Silveira, Angela
    Steinbach, Gerald
    Thorand, Barbara
    Trakalo, Joseph
    Veglia, Fabrizio
    Wennauer, Roman
    Winckler, Wendy
    Zabaneh, Delilah
    Campbell, Harry
    van Duijn, Cornelia
    Uitterlinden, Andre G.
    Hofman, Albert
    Sijbrands, Eric
    Abecasis, Goncalo R.
    Owen, Katharine R.
    Zeggini, Eleftheria
    Trip, Mieke D.
    Forouhi, Nita G.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Eriksson, Johan G.
    Peltonen, Leena
    Noethen, Markus M.
    Balkau, Beverley
    Palmer, Colin N. A.
    Lyssenko, Valeriya
    Tuomi, Tiinamaija
    Isomaa, Bo
    Hunter, David J.
    Qi, Lu
    Shuldiner, Alan R.
    Roden, Michael
    Barroso, Ines
    Wilsgaard, Tom
    Beilby, John
    Hovingh, Kees
    Price, Jackie F.
    Wilson, James F.
    Rauramaa, Rainer
    Lakka, Timo A.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Dedoussis, George
    Njolstad, Inger
    Pedersen, Nancy L.
    Khaw, Kay-Tee
    Wareham, Nicholas J.
    Keinanen-Kiukaanniemi, Sirkka M.
    Saaristo, Timo E.
    Korpi-Hyovalti, Eeva
    Saltevo, Juha
    Laakso, Markku
    Kuusisto, Johanna
    Metspalu, Andres
    Collins, Francis S.
    Mohlke, Karen L.
    Bergman, Richard N.
    Tuomilehto, Jaakko
    Boehm, Bernhard O.
    Gieger, Christian
    Hveem, Kristian
    Cauchi, Stephane
    Froguel, Philippe
    Baldassarre, Damiano
    Tremoli, Elena
    Humphries, Steve E.
    Saleheen, Danish
    Danesh, John
    Ingelsson, Erik
    Ripatti, Samuli
    Salomaa, Veikko
    Erbel, Raimund
    Joeckel, Karl-Heinz
    Moebus, Susanne
    Peters, Annette
    Illig, Thomas
    de Faire, Ulf
    Hamsten, Anders
    Morris, Andrew D.
    Donnelly, Peter J.
    Frayling, Timothy M.
    Hattersley, Andrew T.
    Boerwinkle, Eric
    Melander, Olle
    Kathiresan, Sekar
    Nilsson, Peter M.
    Deloukas, Panos
    Thorsteinsdottir, Unnur
    Groop, Leif C.
    Stefansson, Kari
    Hu, Frank
    Pankow, James S.
    Dupuis, Josee
    Meigs, James B.
    Altshuler, David
    Boehnke, Michael
    McCarthy, Mark I.
    Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes2012In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, no 9, p. 981-+Article in journal (Refereed)
    Abstract [en]

    To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genomewide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.

  • 331.
    Muntlin Athlin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hur kan vi som sjuksköterskor förbättra vården på akutmottagningar för patienter som söker för buksmärta?2010In: Smärta, ISSN 1402-1048, no 3, p. 16-19Article in journal (Other academic)
  • 332.
    Muntlin Athlin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. School of Nursing, University of Adelaide; Department of Emergency Care and Internal Medicine, Uppsala.
    Methods, metrics and research gaps around minimum data sets for nursing practice and fundamental care: A scoping literature review2018In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 27, no 11/12, p. 2230-2247Article in journal (Refereed)
    Abstract [en]

    Aims and objectives

    To examine and map research on minimum data sets linked to nursing practice and the fundamentals of care. Another aim was to identify gaps in the evidence to suggest future research questions to highlight the need for standardisation of terminology around nursing practice and fundamental care.

    Background

    Addressing fundamental care has been highlighted internationally as a response to missed nursing care. Systematic performance measurements are needed to capture nursing practice outcomes.

    Design

    Overview of the literature framed by the scoping study methodology.

    Method

    PubMed and CINAHL were searched using the following inclusion criteria: peer‐reviewed empirical quantitative and qualitative studies related to minimum data sets and nursing practice published in English. No time restrictions were set. Exclusion criteria were as follows: no available full text, reviews and methodological and discursive studies. Data were categorised into one of the fundamentals of care elements.

    Results

    The review included 20 studies published in 1999–2016. Settings were mainly nursing homes or hospitals. Of 14 elements of the fundamentals of care, 11 were identified as measures in the included studies, but their frequency varied. The most commonly identified elements concerned safety, prevention and medication (n = 11), comfort (n = 6) and eating and drinking (n = 5).

    Conclusion

    Studies have used minimum data sets and included variables linked to nursing practices and fundamentals of care. However, the relations of these variables to nursing practice were not always clearly described and the main purpose of the studies was seldom to measure the outcomes of nursing interventions. More robust studies focusing on nursing practice and patient outcomes are warranted.

  • 333.
    Muntlin Athlin, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. School of Nursing, University of Adelaide.
    Brovall, Maria
    Högskolan i Skövde/Institutionen för hälsa och lärande.
    Wengström, Yvonne
    Karolinska Institutet/ Institutionen för Neurobiologi, Vårdvetenskap och Samhälle (NVS), H1, Sektionen för omvårdnad- Omvårdnad 2, Karolinska Universitetssjukhuset; CRU.
    Conroy, Tiffany
    School of Nursing, University of Adelaide, Australia.
    Kitson, Alison
    School of Nursing, University of Adelaide, Australia; Centre for Evidence based Practice South Australia, School of Nursing, The University of Adelaide, Australia; Green Templeton College, University of Oxford, United Kingdom.
    Descriptions of fundamental care needs in cancer care: an exploratory study2018In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 27, no 11-12, p. 2322-2332Article in journal (Refereed)
    Abstract [en]

    Aims and objectives

    To explore the experiences of the fundamentals of care for people with a cancer diagnosis, from diagnosis to after adjuvant treatment.

    Background

    More focus is needed on the experience of people living with cancer, as current cancer care more emphasises on independence and resilience without fully acknowledging that there will be moments in the cancer journey where patients will need ‘basic nursing care’ to manage their symptoms and care pathways.

    Design

    Secondary analysis of qualitative data.

    Method

    Secondary thematic analysis of interview data from 30 people with a diagnosis of breast (n=10), colorectal (n=10) or prostate (n=10) cancer was undertaken.

    Results

    The findings revealed vivid descriptions of the fundamentals of care (i.e. basic needs) and participants described physical, psychosocial and relational aspects of the delivery of care. Both positive (e.g. supportive and kind) and negative (e.g. humiliating) experiences related to the relationship with the healthcare professionals were re-counted and affected the participants' experiences of the fundamentals of care. Participants' accounts of their fundamental care needs were provided without them identifying who, within the health care system, was responsible for providing these needs. Specific nursing interventions were seldom described.

    Conclusion

    Some people with a cancer diagnosis have to strive for help and support from the nursing staff to manage to regain control over their recovery. Nurses in cancer care need to focus on the patients' fundamental care needs to optimise their patients' recovery.

    Relevance to clinical practice

    Cancer patients require support with their fundamental care needs and nurses need to be more aware of this and integrate it into the caring relationship. It is imperative that the complexity of the nurse–patient relationship is acknowledged and that models of care which honour this complexity are used.

  • 334.
    Muntlin Athlin, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. School of Nursing, University of Adelaide.
    Carlsson, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Gunningberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    To Receive or Not to Receive Analgesics in the Emergency Department: The Importance of the Pain Intensity Assessment and Initial Nursing Assessment2015In: Pain Management Nursing, ISSN 1524-9042, E-ISSN 1532-8635, Vol. 16, no 5, p. 743-750Article in journal (Refereed)
    Abstract [en]

    Patients seeking emergency care for abdominal pain still experience poor pain management. Pain intensity is not always seen as a mandatory parameter in the initial nurse assessment. Despite the development of nurse-initiated analgesic protocols, many patients do not receive analgesics in the emergency department. The aim of this study was to describe initial nursing assessment related to pain management and to identify predictors for receiving or not receiving analgesics in the emergency department. The sample consists of 100 patients from an intervention group in a previously undertaken Swedish intervention study. The main findings were that the registered nurses assessed 62 patients as being in need of analgesics, and that 52 of these obtained analgesics. The majority of the patients assessed as not being in need of analgesics did not receive analgesics because they did not want medication. Median value for pain intensity at initial assessment was 6 on the numerical rating scale. The results for the logistic regression (n = 80) showed significant differences between receiving analgesics/not receiving analgesics and the predictor pain intensity (measured at initial nurse assessment). Nurses in emergency departments play a crucial role, in that their initial assessment is of specific importance for the patient's further care and whether the patient may or may not receive analgesics. However, more attention has to be paid to patients' experiences and their expectations regarding the pain management in the emergency department. These complex questions have to be studied further in a more systematic way.

  • 335.
    Muntlin Athlin, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. School of Nursing, University of Adelaide, Australia.
    von Thiele Schwarz, Ulrica
    Karolinska institutet.
    Farrokhnia, Nasim
    Karolinska institutet/Södersjukhuset.
    Effects of multidisciplinary teamwork on lead times and patient flow in the emergency department: a longitudinal interventional cohort study2013In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, E-ISSN 1757-7241, Vol. 21, p. 76-Article in journal (Refereed)
    Abstract [en]

    Background: Long waiting times for emergency care are claimed to be caused by overcrowded emergency departments and non-effective working routines. Teamwork has been suggested as a promising solution to these issues. The aim of the present study was to investigate the effects of teamwork in a Swedish emergency department on lead times and patient flow. Methods: The study was set in an emergency department of a university hospital where teamwork, a multi-professional team responsible for the whole care process for a group of patients, was introduced. The study has a longitudinal non-randomized intervention study design. Data were collected for five two-week periods during a period of 1.5 years. The first part of the data collection used an ABAB design whereby standard procedure (A) was altered weekly with teamwork (B). Then, three follow-ups were conducted. At last follow-up, teamwork was permanently implemented. The outcome measures were: number of patients handled within teamwork time, time to physician, total visit time and number of patients handled within the 4-hour target. Results: A total of 1,838 patient visits were studied. The effect on lead times was only evident at the last follow-up. Findings showed that the number of patients handled within teamwork time was almost equal between the different study periods. At the last follow-up, the median time to physician was significantly decreased by 11 minutes (p = 0.0005) compared to the control phase and the total visit time was significantly shorter at last follow-up compared to control phase (p = <0.0001; 39 minutes shorter on average). Finally, the 4-hour target was met in 71% in the last follow-up compared to 59% in the control phase (p = 0.0005). Conclusions: Teamwork seems to contribute to the quality improvement of emergency care in terms of small but significant decreases in lead times. However, although efficient work processes such as teamwork are necessary to ensure safe patient care, it is likely not sufficient for bringing about larger decreases in lead times or for meeting the 4-hour target in the emergency department.

  • 336. Murray, Christopher J L
    et al.
    Barber, Ryan M
    Foreman, Kyle J
    Ozgoren, Ayse Abbasoglu
    Abd-Allah, Foad
    Abera, Semaw F
    Aboyans, Victor
    Abraham, Jerry P
    Abubakar, Ibrahim
    Abu-Raddad, Laith J
    Abu-Rmeileh, Niveen M
    Achoki, Tom
    Ackerman, Ilana N
    Ademi, Zanfina
    Adou, Arsène K
    Adsuar, José C
    Afshin, Ashkan
    Agardh, Emilie E
    Alam, Sayed Saidul
    Alasfoor, Deena
    Albittar, Mohammed I
    Alegretti, Miguel A
    Alemu, Zewdie A
    Alfonso-Cristancho, Rafael
    Alhabib, Samia
    Ali, Raghib
    Alla, François
    Allebeck, Peter
    Almazroa, Mohammad A
    Alsharif, Ubai
    Alvarez, Elena
    Alvis-Guzman, Nelson
    Amare, Azmeraw T
    Ameh, Emmanuel A
    Amini, Heresh
    Ammar, Walid
    Anderson, H Ross
    Anderson, Benjamin O
    Antonio, Carl Abelardo T
    Anwari, Palwasha
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Arsenijevic, Valentina S Arsic
    Artaman, Al
    Asghar, Rana J
    Assadi, Reza
    Atkins, Lydia S
    Avila, Marco A
    Awuah, Baffour
    Bachman, Victoria F
    Badawi, Alaa
    Bahit, Maria C
    Balakrishnan, Kalpana
    Banerjee, Amitava
    Barker-Collo, Suzanne L
    Barquera, Simon
    Barregard, Lars
    Barrero, Lope H
    Basu, Arindam
    Basu, Sanjay
    Basulaiman, Mohammed O
    Beardsley, Justin
    Bedi, Neeraj
    Beghi, Ettore
    Bekele, Tolesa
    Bell, Michelle L
    Benjet, Corina
    Bennett, Derrick A
    Bensenor, Isabela M
    Benzian, Habib
    Bernabé, Eduardo
    Bertozzi-Villa, Amelia
    Beyene, Tariku J
    Bhala, Neeraj
    Bhalla, Ashish
    Bhutta, Zulfiqar A
    Bienhoff, Kelly
    Bikbov, Boris
    Biryukov, Stan
    Blore, Jed D
    Blosser, Christopher D
    Blyth, Fiona M
    Bohensky, Megan A
    Bolliger, Ian W
    Başara, Berrak Bora
    Bornstein, Natan M
    Bose, Dipan
    Boufous, Soufiane
    Bourne, Rupert R A
    Boyers, Lindsay N
    Brainin, Michael
    Brayne, Carol E
    Brazinova, Alexandra
    Breitborde, Nicholas J K
    Brenner, Hermann
    Briggs, Adam D
    Brooks, Peter M
    Brown, Jonathan C
    Brugha, Traolach S
    Buchbinder, Rachelle
    Buckle, Geoffrey C
    Budke, Christine M
    Bulchis, Anne
    Bulloch, Andrew G
    Campos-Nonato, Ismael R
    Carabin, Hélène
    Carapetis, Jonathan R
    Cárdenas, Rosario
    Carpenter, David O
    Caso, Valeria
    Castañeda-Orjuela, Carlos A
    Castro, Ruben E
    Catalá-López, Ferrán
    Cavalleri, Fiorella
    Çavlin, Alanur
    Chadha, Vineet K
    Chang, Jung-Chen
    Charlson, Fiona J
    Chen, Honglei
    Chen, Wanqing
    Chiang, Peggy P
    Chimed-Ochir, Odgerel
    Chowdhury, Rajiv
    Christensen, Hanne
    Christophi, Costas A
    Cirillo, Massimo
    Coates, Matthew M
    Coffeng, Luc E
    Coggeshall, Megan S
    Colistro, Valentina
    Colquhoun, Samantha M
    Cooke, Graham S
    Cooper, Cyrus
    Cooper, Leslie T
    Coppola, Luis M
    Cortinovis, Monica
    Criqui, Michael H
    Crump, John A
    Cuevas-Nasu, Lucia
    Danawi, Hadi
    Dandona, Lalit
    Dandona, Rakhi
    Dansereau, Emily
    Dargan, Paul I
    Davey, Gail
    Davis, Adrian
    Davitoiu, Dragos V
    Dayama, Anand
    De Leo, Diego
    Degenhardt, Louisa
    Del Pozo-Cruz, Borja
    Dellavalle, Robert P
    Deribe, Kebede
    Derrett, Sarah
    Jarlais, Don C Des
    Dessalegn, Muluken
    Dharmaratne, Samath D
    Dherani, Mukesh K
    Diaz-Torné, Cesar
    Dicker, Daniel
    Ding, Eric L
    Dokova, Klara
    Dorsey, E Ray
    Driscoll, Tim R
    Duan, Leilei
    Duber, Herbert C
    Ebel, Beth E
    Edmond, Karen M
    Elshrek, Yousef M
    Endres, Matthias
    Ermakov, Sergey P
    Erskine, Holly E
    Eshrati, Babak
    Esteghamati, Alireza
    Estep, Kara
    Faraon, Emerito Jose A
    Farzadfar, Farshad
    Fay, Derek F
    Feigin, Valery L
    Felson, David T
    Fereshtehnejad, Seyed-Mohammad
    Fernandes, Jefferson G
    Ferrari, Alize J
    Fitzmaurice, Christina
    Flaxman, Abraham D
    Fleming, Thomas D
    Foigt, Nataliya
    Forouzanfar, Mohammad H
    Fowkes, F Gerry R
    Paleo, Urbano Fra
    Franklin, Richard C
    Fürst, Thomas
    Gabbe, Belinda
    Gaffikin, Lynne
    Gankpé, Fortuné G
    Geleijnse, Johanna M
    Gessner, Bradford D
    Gething, Peter
    Gibney, Katherine B
    Giroud, Maurice
    Giussani, Giorgia
    Dantes, Hector Gomez
    Gona, Philimon
    González-Medina, Diego
    Gosselin, Richard A
    Gotay, Carolyn C
    Goto, Atsushi
    Gouda, Hebe N
    Graetz, Nicholas
    Gugnani, Harish C
    Gupta, Rahul
    Gupta, Rajeev
    Gutiérrez, Reyna A
    Haagsma, Juanita
    Hafezi-Nejad, Nima
    Hagan, Holly
    Halasa, Yara A
    Hamadeh, Randah R
    Hamavid, Hannah
    Hammami, Mouhanad
    Hancock, Jamie
    Hankey, Graeme J
    Hansen, Gillian M
    Hao, Yuantao
    Harb, Hilda L
    Haro, Josep Maria
    Havmoeller, Rasmus
    Hay, Simon I
    Hay, Roderick J
    Heredia-Pi, Ileana B
    Heuton, Kyle R
    Heydarpour, Pouria
    Higashi, Hideki
    Hijar, Martha
    Hoek, Hans W
    Hoffman, Howard J
    Hosgood, H Dean
    Hossain, Mazeda
    Hotez, Peter J
    Hoy, Damian G
    Hsairi, Mohamed
    Hu, Guoqing
    Huang, Cheng
    Huang, John J
    Husseini, Abdullatif
    Huynh, Chantal
    Iannarone, Marissa L
    Iburg, Kim M
    Innos, Kaire
    Inoue, Manami
    Islami, Farhad
    Jacobsen, Kathryn H
    Jarvis, Deborah L
    Jassal, Simerjot K
    Jee, Sun Ha
    Jeemon, Panniyammakal
    Jensen, Paul N
    Jha, Vivekanand
    Jiang, Guohong
    Jiang, Ying
    Jonas, Jost B
    Juel, Knud
    Kan, Haidong
    Karch, André
    Karema, Corine K
    Karimkhani, Chante
    Karthikeyan, Ganesan
    Kassebaum, Nicholas J
    Kaul, Anil
    Kawakami, Norito
    Kazanjan, Konstantin
    Kemp, Andrew H
    Kengne, Andre P
    Keren, Andre
    Khader, Yousef S
    Khalifa, Shams Eldin A
    Khan, Ejaz A
    Khan, Gulfaraz
    Khang, Young-Ho
    Kieling, Christian
    Kim, Daniel
    Kim, Sungroul
    Kim, Yunjin
    Kinfu, Yohannes
    Kinge, Jonas M
    Kivipelto, Miia
    Knibbs, Luke D
    Knudsen, Ann Kristin
    Kokubo, Yoshihiro
    Kosen, Soewarta
    Krishnaswami, Sanjay
    Defo, Barthelemy Kuate
    Bicer, Burcu Kucuk
    Kuipers, Ernst J
    Kulkarni, Chanda
    Kulkarni, Veena S
    Kumar, G Anil
    Kyu, Hmwe H
    Lai, Taavi
    Lalloo, Ratilal
    Lallukka, Tea
    Lam, Hilton
    Lan, Qing
    Lansingh, Van C
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lawrynowicz, Alicia E B
    Leasher, Janet L
    Leigh, James
    Leung, Ricky
    Levitz, Carly E
    Li, Bin
    Li, Yichong
    Li, Yongmei
    Lim, Stephen S
    Lind, Maggie
    Lipshultz, Steven E
    Liu, Shiwei
    Liu, Yang
    Lloyd, Belinda K
    Lofgren, Katherine T
    Logroscino, Giancarlo
    Looker, Katharine J
    Lortet-Tieulent, Joannie
    Lotufo, Paulo A
    Lozano, Rafael
    Lucas, Robyn M
    Lunevicius, Raimundas
    Lyons, Ronan A
    Ma, Stefan
    Macintyre, Michael F
    Mackay, Mark T
    Majdan, Marek
    Malekzadeh, Reza
    Marcenes, Wagner
    Margolis, David J
    Margono, Christopher
    Marzan, Melvin B
    Masci, Joseph R
    Mashal, Mohammad T
    Matzopoulos, Richard
    Mayosi, Bongani M
    Mazorodze, Tasara T
    Mcgill, Neil W
    Mcgrath, John J
    Mckee, Martin
    Mclain, Abigail
    Meaney, Peter A
    Medina, Catalina
    Mehndiratta, Man Mohan
    Mekonnen, Wubegzier
    Melaku, Yohannes A
    Meltzer, Michele
    Memish, Ziad A
    Mensah, George A
    Meretoja, Atte
    Mhimbira, Francis A
    Micha, Renata
    Miller, Ted R
    Mills, Edward J
    Mitchell, Philip B
    Mock, Charles N
    Ibrahim, Norlinah Mohamed
    Mohammad, Karzan A
    Mokdad, Ali H
    Mola, Glen L D
    Monasta, Lorenzo
    Hernandez, Julio C Montañez
    Montico, Marcella
    Montine, Thomas J
    Mooney, Meghan D
    Moore, Ami R
    Moradi-Lakeh, Maziar
    Moran, Andrew E
    Mori, Rintaro
    Moschandreas, Joanna
    Moturi, Wilkister N
    Moyer, Madeline L
    Mozaffarian, Dariush
    Msemburi, William T
    Mueller, Ulrich O
    Mukaigawara, Mitsuru
    Mullany, Erin C
    Murdoch, Michele E
    Murray, Joseph
    Murthy, Kinnari S
    Naghavi, Mohsen
    Naheed, Aliya
    Naidoo, Kovin S
    Naldi, Luigi
    Nand, Devina
    Nangia, Vinay
    Narayan, K M Venkat
    Nejjari, Chakib
    Neupane, Sudan P
    Newton, Charles R
    Ng, Marie
    Ngalesoni, Frida N
    Nguyen, Grant
    Nisar, Muhammad I
    Nolte, Sandra
    Norheim, Ole F
    Norman, Rosana E
    Norrving, Bo
    Nyakarahuka, Luke
    Oh, In-Hwan
    Ohkubo, Takayoshi
    Ohno, Summer L
    Olusanya, Bolajoko O
    Opio, John Nelson
    Ortblad, Katrina
    Ortiz, Alberto
    Pain, Amanda W
    Pandian, Jeyaraj D
    Panelo, Carlo Irwin A
    Papachristou, Christina
    Park, Eun-Kee
    Park, Jae-Hyun
    Patten, Scott B
    Patton, George C
    Paul, Vinod K
    Pavlin, Boris I
    Pearce, Neil
    Pereira, David M
    Perez-Padilla, Rogelio
    Perez-Ruiz, Fernando
    Perico, Norberto
    Pervaiz, Aslam
    Pesudovs, Konrad
    Peterson, Carrie B
    Petzold, Max
    Phillips, Michael R
    Phillips, Bryan K
    Phillips, David E
    Piel, Frédéric B
    Plass, Dietrich
    Poenaru, Dan
    Polinder, Suzanne
    Pope, Daniel
    Popova, Svetlana
    Poulton, Richie G
    Pourmalek, Farshad
    Prabhakaran, Dorairaj
    Prasad, Noela M
    Pullan, Rachel L
    Qato, Dima M
    Quistberg, D Alex
    Rafay, Anwar
    Rahimi, Kazem
    Rahman, Sajjad U
    Raju, Murugesan
    Rana, Saleem M
    Razavi, Homie
    Reddy, K Srinath
    Refaat, Amany
    Remuzzi, Giuseppe
    Resnikoff, Serge
    Ribeiro, Antonio L
    Richardson, Lee
    Richardus, Jan Hendrik
    Roberts, D Allen
    Rojas-Rueda, David
    Ronfani, Luca
    Roth, Gregory A
    Rothenbacher, Dietrich
    Rothstein, David H
    Rowley, Jane T
    Roy, Nobhojit
    Ruhago, George M
    Saeedi, Mohammad Y
    Saha, Sukanta
    Sahraian, Mohammad Ali
    Sampson, Uchechukwu K A
    Sanabria, Juan R
    Sandar, Logan
    Santos, Itamar S
    Satpathy, Maheswar
    Sawhney, Monika
    Scarborough, Peter
    Schneider, Ione J
    Schöttker, Ben
    Schumacher, Austin E
    Schwebel, David C
    Scott, James G
    Seedat, Soraya
    Sepanlou, Sadaf G
    Serina, Peter T
    Servan-Mori, Edson E
    Shackelford, Katya A
    Shaheen, Amira
    Shahraz, Saeid
    Levy, Teresa Shamah
    Shangguan, Siyi
    She, Jun
    Sheikhbahaei, Sara
    Shi, Peilin
    Shibuya, Kenji
    Shinohara, Yukito
    Shiri, Rahman
    Shishani, Kawkab
    Shiue, Ivy
    Shrime, Mark G
    Sigfusdottir, Inga D
    Silberberg, Donald H
    Simard, Edgar P
    Sindi, Shireen
    Singh, Abhishek
    Singh, Jasvinder A
    Singh, Lavanya
    Skirbekk, Vegard
    Slepak, Erica Leigh
    Sliwa, Karen
    Soneji, Samir
    Søreide, Kjetil
    Soshnikov, Sergey
    Sposato, Luciano A
    Sreeramareddy, Chandrashekhar T
    Stanaway, Jeffrey D
    Stathopoulou, Vasiliki
    Stein, Dan J
    Stein, Murray B
    Steiner, Caitlyn
    Steiner, Timothy J
    Stevens, Antony
    Stewart, Andrea
    Stovner, Lars J
    Stroumpoulis, Konstantinos
    Sunguya, Bruno F
    Swaminathan, Soumya
    Swaroop, Mamta
    Sykes, Bryan L
    Tabb, Karen M
    Takahashi, Ken
    Tandon, Nikhil
    Tanne, David
    Tanner, Marcel
    Tavakkoli, Mohammad
    Taylor, Hugh R
    Ao, Braden J Te
    Tediosi, Fabrizio
    Temesgen, Awoke M
    Templin, Tara
    Ten Have, Margreet
    Tenkorang, Eric Y
    Terkawi, Abdullah S
    Thomson, Blake
    Thorne-Lyman, Andrew L
    Thrift, Amanda G
    Thurston, George D
    Tillmann, Taavi
    Tonelli, Marcello
    Topouzis, Fotis
    Toyoshima, Hideaki
    Traebert, Jefferson
    Tran, Bach X
    Trillini, Matias
    Truelsen, Thomas
    Tsilimbaris, Miltiadis
    Tuzcu, Emin M
    Uchendu, Uche S
    Ukwaja, Kingsley N
    Undurraga, Eduardo A
    Uzun, Selen B
    Van Brakel, Wim H
    Van De Vijver, Steven
    van Gool, Coen H
    Van Os, Jim
    Vasankari, Tommi J
    Venketasubramanian, N
    Violante, Francesco S
    Vlassov, Vasiliy V
    Vollset, Stein Emil
    Wagner, Gregory R
    Wagner, Joseph
    Waller, Stephen G
    Wan, Xia
    Wang, Haidong
    Wang, Jianli
    Wang, Linhong
    Warouw, Tati S
    Weichenthal, Scott
    Weiderpass, Elisabete
    Weintraub, Robert G
    Wenzhi, Wang
    Werdecker, Andrea
    Westerman, Ronny
    Whiteford, Harvey A
    Wilkinson, James D
    Williams, Thomas N
    Wolfe, Charles D
    Wolock, Timothy M
    Woolf, Anthony D
    Wulf, Sarah
    Wurtz, Brittany
    Xu, Gelin
    Yan, Lijing L
    Yano, Yuichiro
    Ye, Pengpeng
    Yentür, Gökalp K
    Yip, Paul
    Yonemoto, Naohiro
    Yoon, Seok-Jun
    Younis, Mustafa Z
    Yu, Chuanhua
    Zaki, Maysaa E
    Zhao, Yong
    Zheng, Yingfeng
    Zonies, David
    Zou, Xiaonong
    Salomon, Joshua A
    Lopez, Alan D
    Vos, Theo
    Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition2015In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 386, no 10009, p. 2145-2191Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development.

    METHODS:

    We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time.

    FINDINGS:

    Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries.

    INTERPRETATION:

    Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition-in which increasing sociodemographic status brings structured change in disease burden-is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

    FUNDING:

    Bill & Melinda Gates Foundation.

  • 337. Naghavi, Moshen
    et al.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Murray, Christopher JL
    Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.2015In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 385, no 9963, p. 117-171Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries.

    METHODS: We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions.

    FINDINGS: Global life expectancy for both sexes increased from 65·3 years (UI 65·0-65·6) in 1990, to 71·5 years (UI 71·0-71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8-48·2) to 54·9 million (UI 53·6-56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions.

    INTERPRETATION: For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.

  • 338.
    Nerpin, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Erik
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Jobs, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Association between glomerular filtration rate and endothelial function in an elderly community cohort2012In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 224, no 1, p. 242-246Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Endothelial dysfunction is prevalent among individuals with chronic kidney disease. However, the association between glomerular filtration rate and endothelial function in the community is unclear and needs to be investigated in the general population.

    METHODS: In the community-based Prospective Investigation of the Vasculature of Uppsala Seniors study (PIVUS, n = 952, mean age 70, women 49.3%), we investigated cross-sectional associations between estimated cystatin C-based glomerular filtration rate (eGFR), and 3 measures representing different aspects of endothelial function (endothelial-dependent vasodilation [EDV], endothelial independent vasodilatation [EIDV], and flow-mediated dilatation [FMD]). We also performed pre-specified sub-group analyses in participants with normal eGFR (>60 ml/min/1.73 m(2)).

    RESULTS: In the whole cohort, 10 ml/min/1.73 m(2) higher eGFR was associated with 3% higher EDV (p = 0.001) and 2% higher EIDV (p = 0.007), adjusted for age and sex. The associations were attenuated and no longer statistically significant after adjusting for established cardiovascular risk factors. In participants with eGFR >60 ml/min/1.73 m(2), 10 ml higher eGFR was associated with 2% higher EDV (p = 0.04) after adjusting for sex and age. eGFR was not associated to FMD in any model or sub-sample.

    CONCLUSION: This community-based study suggests that eGFR is associated with endothelial function also in persons with normal kidney function, but that this association is largely explained by confounding by established cardiovascular risk factors. Thus, our data do not support the notion of a direct causal interplay between renal and vascular function prior to the development of CKD.

  • 339.
    Nerpin, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Högskolan Dalarna-Medicinsk vetenskap.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Jobs, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Högskolan Dalarna Medicinsk vetenskap.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Högskolan Dalarna Medicinsk vetenskap.
    The association between glomerular filtration rate and left ventricular function in two independent community-based cohorts of elderly2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, no 11, p. 2069-2074Article in journal (Refereed)
    Abstract [en]

    The cardiorenal syndrome, the detrimental bi-directional interplay between symptomatic heart failure and chronic kidney disease, is a major clinical challenge. Nonetheless, it is unknown if this interplay begins already at an asymptomatic stage. Therefore we investigated whether the glomerular filtration rate (GFR) is associated with left ventricular function in participants free from clinical heart failure and with a left ventricular ejection fraction (LVEF) > 40% and with pre-specified sub-group analyses in individuals with a GFR > 60 mL/min/m(2). Two independent community-based cohorts were used; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 911; 50% women; mean age: 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 538; mean age: 71 years). We investigated cross-sectional association between cystatin C-based GFR (estimated glomerular function [eGFR]) and systolic (LVEF), diastolic- (isovolumic relaxation time [IVRT]) and global left ventricular function (myocardial performance index [MPI]) determined by echocardiography. In both PIVUS and ULSAM, higher eGFR was significantly associated with higher LVEF (P = 0.004 [PIVUS] and P = 0.005 [ULSAM]). In PIVUS, higher eGFR was significantly associated with lower IVRT (P = 0.001) and MPI (P = 0.006), in age- and sex-adjusted models. After further adjustment for cardiovascular risk factors, the association between higher eGFR and higher LVEF was still statistically significant (P = 0.008 [PIVUS] and P = 0.02 [ULSAM]). In PIVUS, the age- and sex-adjusted association between eGFR and left ventricular function was similar in participants with eGFR > 60 mL/min/m(2). Our data suggest that the interplay between kidney and heart function begins prior to the development of symptomatic heart failure and kidney disease.

  • 340.
    Ng, Esther
    et al.
    Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine. Uppsala Univ, Dept Med Sci Occupat & Environm Med, S-75185 Uppsala, Sweden..
    Lindgren, Cecilia
    Harvard Univ, Inst Technol, Broad Inst Massachusetts, Cambridge, MA 02142 USA..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mahajan, Anubha
    Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Morris, Andrew
    Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Genome-wide association study of toxic metals and trace elements reveals novel associations2015In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, no 16, p. 4739-4745Article in journal (Refereed)
    Abstract [en]

    The accumulation of toxic metals in the human body is influenced by exposure and mechanisms involved in metabolism, some of which may be under genetic control. This is the first genome-wide association study to investigate variants associated with whole blood levels of a range of toxic metals. Eleven toxic metals and trace elements (aluminium, cadmium, cobalt, copper, chromium, mercury, manganese, molybdenum, nickel, lead and zinc) were assayed in a cohort of 949 individuals using mass spectrometry. DNA samples were genotyped on the Infinium Omni Express bead microarray and imputed up to reference panels from the 1000 Genomes Project. Analyses revealed two regions associated with manganese level at genome-wide significance, mapping to 4q24 and 1q41. The lead single nucleotide polymorphism(SNP) in the 4q24 locus was rs13107325 (P-value = 5.1 x 10(-11), beta = -0.77), located in an exon of SLC39A8, which encodes a protein involved in manganese and zinc transport. The lead SNP in the 1q41 locus is rs1776029 (P-value = 2.2 x 10(-14), beta = -0.46). The SNP lies within the intronic region of SLC30A10, another transporter protein. Among other metals, the loci 6q14.1 and 3q26.32 were associated with cadmium and mercury levels (P = 1.4x10(-10), beta = -1.2 and P = 1.8x10(-9), beta = -1.8, respectively). Whole blood measurements of toxicmetals are associated with genetic variants in metal transporter genes and others. This is relevant in inferring metabolic pathways of metals and identifying subsets of individuals who may be more susceptible to metal toxicity.

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  • 341. Ng, Esther
    et al.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Mahajan, Anubha
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lindgren, Cecilia M
    van Bavel, Bert
    Morris, Andrew P
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample2015In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 140, p. 95-101Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Polychlorinated biphenyls (PCBs) are a group of man-made environmental pollutants which accumulate in humans with adverse health effects. To date, very little effort has been devoted to the study of the metabolism of PCBs on a genome-wide level.

    OBJECTIVES: Here, we conducted a genome-wide association study (GWAS) to identify genomic regions involved in the metabolism of PCBs.

    METHODS: Plasma levels of 16 PCBs ascertained in a cohort of elderly individuals from Sweden (n=1016) were measured using gas chromatography-high resolution mass spectrophotometry (GC-HRMS). DNA samples were genotyped on the Infinium Omni Express bead microarray, and imputed up to reference panels from the 1000 Genomes Project. Association testing was performed in a linear regression framework under an additive model.

    RESULTS: Plasma levels of PCB-99 demonstrated genome-wide significant association with single nucleotide polymorphisms (SNPs) mapping to chromosome 19q13.2. The SNP with the strongest association was rs8109848 (p=3.7×10(-13)), mapping to an intronic region of CYP2B6. Moreover, when all PCBs were conditioned on PCB-99, further signals were revealed for PCBs -74, -105 and -118, mapping to the same genomic region. The lead SNPs were rs8109848 (p=3.8×10(-12)) for PCB-118, rs4802104 (p=1.4×10(-9)) for PCB-74 and rs4803413 (p=2.5×10(-9)) for PCB-105, all of which map to CYP2B6.

    CONCLUSIONS: In our study, we found plasma levels of four lower-chlorinated PCBs to be significantly associated with the genetic region mapping to the CYP2B6 locus. These findings show that CYP2B6 is of importance for the metabolism of PCBs in humans, and may help to identify individuals who may be susceptible to PCB toxicity.

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  • 342.
    Nikpay, Majid
    et al.
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Goel, Anuj
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Won, Hong-Hee
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA USA..
    Hall, Leanne M.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England..
    Willenborg, Christina
    Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany.;DZHK German Res Ctr Cardiovasc Res, Lubeck, Germany..
    Kanoni, Stavroula
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Saleheen, Danish
    Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.;Ctr Noncommunicable Dis, Karachi, Pakistan..
    Kyriakou, Theodosios
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Hopewell, Jemma C.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England..
    Webb, Thomas R.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Zeng, Lingyao
    Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Dehghan, Abbas
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Alver, Maris
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia..
    Armasu, Sebastian M.
    Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA..
    Auro, Kirsi
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland..
    Bjonnes, Andrew
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA USA..
    Chen, Shufeng
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China..
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland..
    Franceschini, Nora
    Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA..
    Gieger, Christian
    DZHK German Ctr Cardiovasc Res, Munich, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Grace, Christopher
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Huang, Jie
    Wellcome Trust Sanger Inst, Hinxton, England..
    Hwang, Shih-Jen
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Kim, Yun Kyoung
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea..
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Vth Dept Med Nephrol Hypertensiol Endocrinol Diab, Mannheim, Germany..
    Lau, King Wai
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England..
    Lu, Xiangfeng
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    Morrison, Alanna C.
    Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Houston, TX 77030 USA..
    Pervjakova, Natalia
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland..
    Qu, Liming
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA..
    Rose, Lynda M.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA..
    Salfati, Elias
    Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Saxena, Richa
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA..
    Scholz, Markus
    Univ Leipzig, Fac Med, Inst Med Informat Stat & Epidemiol, D-04109 Leipzig, Germany.;LIFE Res Ctr Civilizat Dis, Leipzig, Germany..
    Smith, Albert V.
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Tikkanen, Emmi
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Uitterlinden, Andre
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Yang, Xueli
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China..
    Zhang, Weihua
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England..
    Zhao, Wei
    Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA..
    de Andrade, Mariza
    Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA..
    de Vries, Paul S.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    van Zuydam, Natalie R.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Dundee, Med Res Inst, Dundee, Scotland..
    Anand, Sonia S.
    McMaster Univ, Dept Med, Populat Hlth Res Inst, Hamilton Hlth Sci, Hamilton, ON, Canada..
    Bertram, Lars
    Univ Lubeck, Inst Neurogenet & Integrat, Platform Genome Analyt, Lubeck, Germany.;Univ Lubeck, Inst Expt Gen, Platform Genome Analyt, Lubeck, Germany.;Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, Neuroepidemiol & Ageing Res Unit, London, England..
    Beutner, Frank
    LIFE Res Ctr Civilizat Dis, Leipzig, Germany.;Univ Leipzig, Heart Ctr Leipzig, Cardiol, D-04109 Leipzig, Germany..
    Dedoussis, George
    Harokopio Univ, Dept Dietet Nutr, Athens, Greece..
    Frossard, Philippe
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Gauguier, Dominique
    INSERM, Ctr Rech Cordeliers, UMRS 1138, Paris, France..
    Goodall, Alison H.
    Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England.;Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England..
    Gottesman, Omri
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Haber, Marc
    Lebanese Amer Univ, Sch Med, Beirut, Lebanon..
    Han, Bok-Ghee
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea..
    Huang, Jianfeng
    Peking Union Med Coll, Beijing 100021, Peoples R China.;Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, Hypertens Div, Beijing 100730, Peoples R China..
    Jalilzadeh, Shapour
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Kessler, Thorsten
    Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany.;Klinikum Rechts Der Isar, Munich, Germany..
    Koenig, Inke R.
    DZHK German Res Ctr Cardiovasc Res, Lubeck, Germany.;Univ Lubeck, Inst Med Biometrie & Stat, Lubeck, Germany..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lieb, Wolfgang
    Univ Kiel, Inst Epidemiol, Kiel, Germany..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Broad Inst MIT & Harvard Univ, Cambridge, MA USA..
    Lokki, Marja-Liisa
    Univ Helsinki, Haartman Inst, Transplantat Lab, Helsinki, Finland..
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Mallick, Nadeem H.
    Punjab Inst Cardiol, Lahore, Pakistan..
    Mehra, Narinder
    All India Inst Med Sci, New Delhi, India..
    Meitinger, Thomas
    DZHK German Ctr Cardiovasc Res, Munich, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Humangenet, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany..
    Memon, Fazal-ur-Rehman
    Red Crescent Inst Cardiol, Hyderabad, Andhra Pradesh, Pakistan..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England..
    Nieminen, Markku S.
    Univ Helsinki, Cent Hosp, Dept Med, Dept Cardiol, Helsinki, Finland..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Peters, Annette
    DZHK German Ctr Cardiovasc Res, Munich, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Rallidis, Loukianos S.
    Univ Athens, Sch Med, Attikon Hosp, Dept Cardiol 2, GR-11527 Athens, Greece..
    Rasheed, Asif
    Ctr Noncommunicable Dis, Karachi, Pakistan.;Red Crescent Inst Cardiol, Hyderabad, Andhra Pradesh, Pakistan..
    Samuel, Maria
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Shah, Svati H.
    Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA..
    Sinisalo, Juha
    Univ Helsinki, Cent Hosp, Dept Med, Dept Cardiol, Helsinki, Finland..
    Stirrups, Kathleen E.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Univ Cambridge, Dept Haematol, Cambridge, England..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Wang, Laiyuan
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China.;Natl Human Genome Ctr Beijing, Beijing, Peoples R China..
    Zaman, Khan S.
    Natl Inst Cardiovasc Dis, Karachi, Pakistan..
    Ardissino, Diego
    Univ Parma, Azienda Osped, Div Cardiol, I-43100 Parma, Italy.;Assoc Studio Trombosi Cardiol, Pavia, Italy..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Buring, Julie E.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA..
    Chambers, John C.
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England..
    Collins, Rory
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England..
    Cupples, L. Adrienne
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Danesh, John
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Demuth, Ilja
    Berlin Aging Study 2, Berlin, Germany.;Charite, Res Grp Geriatr, D-13353 Berlin, Germany.;Charite, Inst Med & Human Genet, D-13353 Berlin, Germany..
    Elosua, Roberto
    Inst Hosp Mar Invest Med IMIM, Grp Epidemiol & Genet Cardiovasc, Barcelona, Spain..
    Epstein, Stephen E.
    MedStar Washington Hosp Ctr, MedStar Heart & Vasc Inst, Washington, DC USA..
    Esko, Tonu
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Boston Childrens Hosp, Div Endocrinol & Basic & Translat Obes Res, Boston, MA USA.;Harvard Univ, Sch Med, Dept Genet, Boston, MA USA..
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA..
    Franco, Oscar H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Franzosi, Maria Grazia
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy..
    Granger, Christopher B.
    Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA..
    Gu, Dongfeng
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Hall, Alistair S.
    Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden..
    Harris, Tamara B.
    NIA, Lab Epidemiol Demog & Biometry, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Hazen, Stanley L.
    Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA..
    Hengstenberg, Christian
    Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Hofman, Albert
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Iribarren, Carlos
    Kaiser Permanente Div Res, Oakland, CA USA..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.;Interunivers Cardiol Inst Netherlands, Utrecht, Netherlands..
    Karhunen, Pekka J.
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Forens Med, FIN-33101 Tampere, Finland..
    Kim, Bong-Jo
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea..
    Kooner, Jaspal S.
    Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England.;Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Cardiovasc Sci, London, England..
    Kullo, Iftikhar J.
    Mayo Clin, Dept Med, Cardiovasc Dis, Rochester, MN USA..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA..
    Melander, Olle
    Lund Univ, Univ Hosp Malmo, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia..
    Maerz, Winfried
    Heidelberg Univ, Med Fac Mannheim, Vth Dept Med Nephrol Hypertensiol Endocrinol Diab, Mannheim, Germany.;Synlab Acad, Synlab Serv, Mannheim, Germany.;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria..
    Palmer, Colin N.
    Univ Dundee, Med Res Inst, Dundee, Scotland..
    Perola, Markus
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland..
    Quertermous, Thomas
    Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA..
    Rader, Daniel J.
    Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA..
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA USA..
    Ripatti, Samuli
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Wellcome Trust Sanger Inst, Hinxton, England.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Roberts, Robert
    Univ Ottawa, Inst Heart, Ottawa, ON, Canada..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland..
    Sanghera, Dharambir K.
    Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Coll Med, Oklahoma City, OK 73190 USA.;Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73190 USA.;Oklahoma Ctr Neurosci, Oklahoma City, OK USA..
    Schwartz, Stephen M.
    Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98104 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Seedorf, Udo
    Univ Med Ctr Hamburg Eppendorf, Ctr Dent & Oral Med, Dept Prosthet Dent, Hamburg, Germany..
    Stewart, Alexandre F.
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Stott, David J.
    Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Thiery, Joachim
    LIFE Res Ctr Civilizat Dis, Leipzig, Germany.;Univ Hosp Leipzig, Fac Med, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany..
    Zalloua, Pierre A.
    Lebanese Amer Univ, Sch Med, Beirut, Lebanon.;Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA..
    O'Donnell, Christopher J.
    NHLBI, Framingham Heart Study, Framingham, MA USA.;NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.;Massachusetts Gen Hosp, Cardiol Div, Boston, MA 02114 USA..
    Reilly, Muredach P.
    Assimes, Themistocles L.
    Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA..
    Thompson, John R.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Erdmann, Jeanette
    Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany.;DZHK German Res Ctr Cardiovasc Res, Lubeck, Germany..
    Clarke, Robert
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England..
    Watkins, Hugh
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Kathiresan, Sekar
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA USA..
    McPherson, Ruth
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Deloukas, Panos
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21413, Saudi Arabia..
    Schunkert, Heribert
    Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Farrall, Martin
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease2015In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, no 10, p. 1121-1130Article in journal (Refereed)
    Abstract [en]

    Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.

  • 343.
    Nilsen, Tom
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Serum calprotectin levels in elderly males and females without bacterial or viral infections2014In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 47, no 12, p. 1065-1068Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Calprotectin is released from activated leukocytes and calprotectin can thus be used as a marker for leukocyte activation. Faeces calprotectin is not only used as a marker for inflammatory bowel disease but can also be used to detect leukocyte activation in other body fluids. The aim of the present study was to study serum calprotectin levels in non-infected elderly individuals to establish reference intervals for the marker.

    METHODS: Serum calprotectin was analyzed by immunoturbidimetry in 75year old females and males without known infections. Individuals with CRP>20mg/L were excluded as this could indicate a subclinical infection. The calprotectin levels in the remaining 713 individuals were used to calculate reference values for this population. The Spearman rank correlations between calprotectin and 27 other laboratory biomarkers were also investigated.

    RESULTS: There was a strong positive Spearman rank correlation between calprotectin and CRP (p<0.000001) and alkaline phosphatase (p<0.000001). There were also significant negative correlations between calprotectin and ApoA1 and direct HDL-cholesterol.

    CONCLUSIONS: The reference interval for serum-calprotectin for all study subjects was 0.3-2.6mg/L. Leukocyte alkaline phosphatase contributes to serum alkaline phosphatase levels.

  • 344.
    Nilsson, Bo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ekdahl, Kristina Nilsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Plasma concentrations of C3 and C4 are linked to cardiovascular risk factors and to the metabolic syndrome2013In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 56, no 3 SI, p. 252-252Article in journal (Other academic)
  • 345.
    Nilsson, Bo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Hamad, Osama A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hänni, Arvo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ekdahl, Kristina N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    C3 And C4 Are Strongly Related To Adipose Tissue Variables And Cardiovascular Risk Factors2014In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 44, no 6, p. 587-596Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In several reports C3 and C4 have been linked to diabetes and cardiovascular disease (CVD). Here we investigate this link and the degree of C3 activation in elderly individuals.

    METHODS: In the present study, C3 and C4 and the activation fragment C3a-desArg were analyzed in 1016 subjects aged 70, in which blood pressure, lipid variables and fasting blood glucose were assessed.

    RESULTS: C3 levels were related to all the investigated classical cardiovascular risk factors and the metabolic syndrome (BMI, waist circumference, fat distribution, blood pressure, blood glucose levels, TG) except total cholesterol and LDL-cholesterol in a highly significant fashion (Spearman up to 0,5; p<0.0001). C4 and C3a-desArg were associated in the same fashion but less significantly, while the ratios C4/C3 or C3a-desArg/C3 were not, indicating that the association was not directly related to complement activation. The levels C3 and to a lesser degree C4 and C3a-desArg, were associated particularly to CRP, but also to E-selectin and ICAM-1. In addition, C3 and C4 levels were shown to decline significantly in 15 female subjects enrolled in a weight-reduction program over 4 months.

    CONCLUSION: A strong relation between C3, C4 and C3a-desArg levels, adipose tissue and risk factors of CVD was established. The data support that the adipose tissue produces complement components and generates initiators of inflammation, such as C3a and C5a, able to trigger a cyto/chemokine response, in proportion to the amount of adipose tissue. This corroborates the concept that complement contributes to the low-grade inflammation associated with obesity. This article is protected by copyright. All rights reserved.

  • 346.
    Nilsson, Erik
    et al.
    Orebro Univ, Sch Med Sci, Dept Internal Med, Orebro, Sweden;Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Stockholm, Sweden.
    Rudholm, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Stenvinkel, Peter
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Stockholm, Sweden.
    Arnlov, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Pregnancy-associated plasma protein A and mortality in haemodialysis2018In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 48, no 8, article id e12959Article in journal (Refereed)
    Abstract [en]

    BackgroundElevated pregnancy-associated plasma protein A (PAPP-A) levels are associated with increased risk of death in ischaemic heart disease as well as in haemodialysis patients. Previous research indicates that the prognostic value of PAPP-A may be stronger in patients with concomitant diabetes mellitus or signs of inflammation. We studied the association between PAPP-A and outcomes in prevalent haemodialysis patients and hypothesized that diabetes mellitus and inflammation status act as effect modifiers. Materials and MethodsCirculating PAPP-A levels were quantified using ELISA. Cox proportional hazards and quantile regression models were used for associations between PAPP-A and mortality. PAPP-A levels were log-transformed for Normality. ResultsDuring 60-month follow-up, 37 (40%) of the 92 participants died. Higher PAPP-A was associated with increased risk of mortality in unadjusted analysis (HR per SD=1.4, 95% CI=1-1.9, P=.03) and when adjusted for confounders and cardiovascular risk factors (HR=1.8, 95% CI=1.18-2.73, P=.006). An interaction between PAPP-A levels and diabetes mellitus on mortality was found (HR for the multiplicative interaction term=2.74 95% CI=1.02-7.37, P=.05). In a quantile regression adjusted for age and sex, one SD increase in PAPP-A was associated with 22months shorter estimated time until 25% of the patients died (95% CI -35 to -9.1months). ConclusionsIncreased PAPP-A levels are associated with higher all-cause mortality in prevalent haemodialysis patients with concomitant diabetes mellitus.

  • 347.
    Nordenskjöld, Richard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Simmons, Andrew
    Brooks, Samantha J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Intracranial volume estimated with commonly used methods could introduce bias in studies including brain volume measurements2013In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 83, p. 355-360Article in journal (Refereed)
    Abstract [en]

    In brain volumetric studies, intracranial volume (ICV) is often used as an estimate of pre-morbid brain size as well as to compensate for inter-subject variations in head size. However, if the estimated ICV is biased by for example gender or atrophy, it could introduce errors in study results. To evaluate how two commonly used methods for ICV estimation perform, computer assisted reference segmentations were created and evaluated. Segmentations were created for 399 MRI volumes from 75-year-old subjects, with 53 of these subjects having an additional scan and segmentation created at age 80. ICV estimates from Statistical Parametric Mapping (SPM, version 8) and Freesurfer (FS, version 5.1.0) were compared to the reference segmentations, and bias related to skull size (approximated with the segmentation measure), gender or atrophy were tested for. The possible ICV related effect on associations between normalized hippocampal volume and factors gender, education and cognition was evaluated by normalizing hippocampal volume with different ICV measures. Excellent agreement was seen for inter- (r=0.999) and intra- (r=0.999) operator reference segmentations. Both SPM and FS overestimated ICV. SPM showed bias associated with gender and atrophy while FS showed bias dependent on skull size. All methods showed good correlation between time points in the longitudinal data (reference: 0.998, SPM: 0.962, FS: 0.995). Hippocampal volume showed different associations with cognition and gender depending on which ICV measure was used for hippocampal volume normalization. These results show that the choice of method used for ICV estimation can bias results in studies including brain volume measurements.

  • 348.
    Nowak, C.
    et al.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden.
    Carlsson, A. C.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden.
    Östgren, C. J.
    Linkoping Univ, Linkoping, Sweden.
    Nyström, F. H.
    Linkoping Univ, Linkoping, Sweden.
    Alam, M.
    Dalarna Univ, Falun, Sweden.
    Feldreich, T. R.
    Dalarna Univ, Falun, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Roig, J. J. Carrero
    Karolinska Inst, Solna, Sweden.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Cordeiro, A. C.
    Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, E.
    Stanford Univ, Sch Med, Stanford, CA 94305 USA.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Arnlöv, J.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden;Dalarna Univ, Falun, Sweden.
    Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S65-S65Article in journal (Other academic)
  • 349.
    Nowak, Christoph
    et al.
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Alfred Nobels Alle 23, SE-14183 Huddinge, Sweden.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Alfred Nobels Alle 23, SE-14183 Huddinge, Sweden.
    Östgren, Carl Johan
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Nyström, Fredrik H.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Alam, Moudud
    Dalarna Univ, Sch Technol & Business Studies Stat, Falun, Sweden.
    Feldreich, Tobias
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Carrero, Juan-Jesus
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Cordeiro, Antonio C.
    Dante Pazzanese Inst Cardiol, Dept Hypertens & Nephrol, Sao Paulo, Brazil.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ärnlöv, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Alfred Nobels Alle 23, SE-14183 Huddinge, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 8, p. 1748-1757Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. Methods We combined data from six prospective epidemiological studies of 30-77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularised Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. Results Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (+/- SD) of 6.4 +/- 2.3 years. We replicated associations (< 5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)-12, IL-27 subunit alpha (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. Conclusions/interpretation We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardiovascular event.

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  • 350.
    Nowak, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Hetty, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Castillejo-Lopez, Casimiro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ganna, Andrea
    Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA;Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Cook, Naomi L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Broeckling, Corey D.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.
    Prenni, Jessica E.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.
    Shen, Xia
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance2018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 8691Article in journal (Refereed)
    Abstract [en]

    Insulin resistance (IR) predisposes to type 2 diabetes and cardiovascular disease but its causes are incompletely understood. Metabolic challenges like the oral glucose tolerance test (OGTT) can reveal pathogenic mechanisms. We aimed to discover associations of IR with metabolite trajectories during OGTT. In 470 non-diabetic men (age 70.6 +/- 0.6 years), plasma samples obtained at 0, 30 and 120 minutes during an OGTT were analyzed by untargeted liquid chromatography-mass spectrometry metabolomics. IR was assessed with the hyperinsulinemic-euglycemic clamp method. We applied age-adjusted linear regression to identify metabolites whose concentration change was related to IR. Nine trajectories, including monounsaturated fatty acids, lysophosphatidylethanolamines and a bile acid, were significantly associated with IR, with the strongest associations observed for medium-chain acylcarnitines C10 and C12, and no associations with L-carnitine or C2-, C8-, C14- or C16-carnitine. Concentrations of C10-and C12-carnitine decreased during OGTT with a blunted decline in participants with worse insulin resistance. Associations persisted after adjustment for obesity, fasting insulin and fasting glucose. In mouse 3T3-L1 adipocytes exposed to different acylcarnitines, we observed blunted insulin-stimulated glucose uptake after treatment with C10-or C12-carnitine. In conclusion, our results identify medium-chain acylcarnitines as possible contributors to IR.

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