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  • 101.
    Fall, Tove
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hägg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Maegi, Reedik
    Ploner, Alexander
    Fischer, Krista
    Horikoshi, Momoko
    Sarin, Antti-Pekka
    Thorleifsson, Gudmar
    Ladenvall, Claes
    Kals, Mart
    Kuningas, Maris
    Draisma, Harmen H. M.
    Ried, Janina S.
    van Zuydam, Natalie R.
    Huikari, Ville
    Mangino, Massimo
    Sonestedt, Emily
    Benyamin, Beben
    Nelson, Christopher P.
    Rivera, Natalia V.
    Kristiansson, Kati
    Shen, Huei-yi
    Havulinna, Aki S.
    Dehghan, Abbas
    Donnelly, Louise A.
    Kaakinen, Marika
    Nuotio, Marja-Liisa
    Robertson, Neil
    de Bruijn, Renee F. A. G.
    Ikram, M. Arfan
    Amin, Najaf
    Balmforth, Anthony J.
    Braund, Peter S.
    Doney, Alexander S. F.
    Doering, Angela
    Elliott, Paul
    Esko, Tonu
    Franco, Oscar H.
    Gretarsdottir, Solveig
    Hartikainen, Anna-Liisa
    Heikkila, Kauko
    Herzig, Karl-Heinz
    Holm, Hilma
    Hottenga, Jouke Jan
    Hypponen, Elina
    Illig, Thomas
    Isaacs, Aaron
    Isomaa, Bo
    Karssen, Lennart C.
    Kettunen, Johannes
    Koenig, Wolfgang
    Kuulasmaa, Kari
    Laatikainen, Tiina
    Laitinen, Jaana
    Lindgren, Cecilia
    Lyssenko, Valeriya
    Laara, Esa
    Rayner, Nigel W.
    Mannisto, Satu
    Pouta, Anneli
    Rathmann, Wolfgang
    Rivadeneira, Fernando
    Ruokonen, Aimo
    Savolainen, Markku J.
    Sijbrands, Eric J. G.
    Small, Kerrin S.
    Smit, Jan H.
    Steinthorsdottir, Valgerdur
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Taanila, Anja
    Tobin, Martin D.
    Uitterlinden, Andre G.
    Willems, Sara M.
    Willemsen, Gonneke
    Witteman, Jacqueline
    Perola, Markus
    Evans, Alun
    Ferrieres, Jean
    Virtamo, Jarmo
    Kee, Frank
    Tregouet, David-Alexandre
    Arveiler, Dominique
    Amouyel, Philippe
    Ferrario, Marco M.
    Brambilla, Paolo
    Hall, Alistair S.
    Heath, AndrewC.
    Madden, Pamela A. F.
    Martin, Nicholas G.
    Montgomery, Grant W.
    Whitfield, John B.
    Jula, Antti
    Knekt, Paul
    Oostra, Ben
    van Duijn, Cornelia M.
    Penninx, Brenda W. J. H.
    Smith, George Davey
    Kaprio, Jaakko
    Samani, Nilesh J.
    Gieger, Christian
    Peters, Annette
    Wichmann, H. -Erich
    Boomsma, Dorret I.
    de Geus, Eco J. C.
    Tuomi, TiinaMaija
    Power, Chris
    Hammond, Christopher J.
    Spector, Tim D.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Orho-Melander, Marju
    Palmer, Colin Neil Alexander
    Morris, Andrew D.
    Groop, Leif
    Jarvelin, Marjo-Riitta
    Salomaa, Veikko
    Vartiainen, Erkki
    Hofman, Albert
    Ripatti, Samuli
    Metspalu, Andres
    Thorsteinsdottir, Unnur
    Stefansson, Kari
    Pedersen, Nancy L.
    McCarthy, Mark I.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Prokopenko, Inga
    The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis2013Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 10, nr 6, s. e1001474-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.

  • 102.
    Fall, Tove
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hägg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ploner, Alexander
    Mägi, Reedik
    Fischer, Krista
    Draisma, Harmen H M
    Sarin, Antti-Pekka
    Benyamin, Beben
    Ladenvall, Claes
    Åkerlund, Mikael
    Kals, Mart
    Esko, Tõnu
    Nelson, Christopher P
    Kaakinen, Marika
    Huikari, Ville
    Mangino, Massimo
    Meirhaeghe, Aline
    Kristiansson, Kati
    Nuotio, Marja-Liisa
    Kobl, Michael
    Grallert, Harald
    Dehghan, Abbas
    Kuningas, Maris
    de Vries, Paul S
    de Bruijn, Renée F A G
    Willems, Sara M
    Heikkilä, Kauko
    Silventoinen, Karri
    Pietiläinen, Kirsi H
    Legry, Vanessa
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Goumidi, Louisa
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Strauch, Konstantin
    Koenig, Wolfgang
    Lichtner, Peter
    Herder, Christian
    Palotie, Aarno
    Menni, Cristina
    Uitterlinden, André G
    Kuulasmaa, Kari
    Havulinna, Aki S
    Moreno, Luis A
    Gonzalez-Gross, Marcela
    Evans, Alun
    Tregouet, David-Alexandre
    Yarnell, John W G
    Virtamo, Jarmo
    Ferrières, Jean
    Veronesi, Giovanni
    Perola, Markus
    Arveiler, Dominique
    Brambilla, Paolo
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Kaprio, Jaakko
    Hofman, Albert
    Stricker, Bruno H
    van Duijn, Cornelia M
    Ikram, M Arfan
    Franco, Oscar H
    Cottel, Dominique
    Dallongeville, Jean
    Hall, Alistair S
    Jula, Antti
    Tobin, Martin D
    Penninx, Brenda W
    Peters, Annette
    Gieger, Christian
    Samani, Nilesh J
    Montgomery, Grant W
    Whitfield, John B
    Martin, Nicholas G
    Groop, Leif
    Spector, Tim D
    Magnusson, Patrik K
    Amouyel, Philippe
    Boomsma, Dorret I
    Nilsson, Peter M
    Järvelin, Marjo-Riitta
    Lyssenko, Valeriya
    Metspalu, Andres
    Strachan, David P
    Salomaa, Veikko
    Ripatti, Samuli
    Pedersen, Nancy L
    Prokopenko, Inga
    McCarthy, Mark I
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Age- and sex-specific causal effects of adiposity on cardiovascular risk factors2015Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 64, nr 5, s. 1841-1852Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.

  • 103. Fall, Tove
    et al.
    Shiue, Ivy
    af Geijerstam, Per Bergea
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Relations of circulating vitamin D concentrations with left ventricular geometry and function2012Ingår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 14, nr 9, s. 985-991Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Vitamin D deficiency has been associated with risk of overt cardiovascular disease (CVD), but associations with subclinical disease are not well characterized. Hence, we examined associations of circulating vitamin D concentrations and left ventricular (LV) geometry and function by echocardiography at baseline and after 5 years in a community-based study. In the PIVUS study, we measured serum 25-dihydroxyvitamin-D (25-OH D) at age 70 and performed echocardiography including LV mass, wall thickness, end-diastolic diameter, end-systolic diameter (LVESD), left atrial diameter, fractional shortening, ejection fraction, isovolumic relaxation time, and E/A ratio at both age 70 and 75. We included 870 participants (52 women) without prior myocardial infarctions, heart failure, or prevalent valvular disease. After adjusting for potential confounders, 25-OH D at baseline was found to be significantly associated with LVESD, fractional shortening, and ejection fraction (, 0.42 mm, P 0.03; , 0.70, P 0.03; and , 0.91 P 0.01, respectively), per 1 SD increase in 25-OH D (SD 20 nmol/L) at baseline. In longitudinal analyses, vitamin D levels at baseline were not significantly associated with change in LV geometry and function after 5 years. In our community-based study among the elderly, we found higher circulating vitamin D concentrations to be associated cross-sectionally with better LV systolic function and smaller LVESD at baseline. The association persisted after adjusting for several potential confounders, including cardiovascular risk factors and calcium, phosphate, and parathyroid hormone levels. Randomized clinical trials are needed to establish firmly or refute a causal relationship between vitamin D levels and changes in LV geometry and function.

  • 104.
    Feldreich, T
    et al.
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.; Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Stockholm, Sweden.
    Carlsson, Axel C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Stockholm, Sweden.
    Helmersson, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.; Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Stockholm, Sweden .
    Urinary Osteopontin Predicts Incident Chronic Kidney Disease, while Plasma Osteopontin Predicts Cardiovascular Death in Elderly Men2017Ingår i: Cardiorenal Medicine, Vol. 7, nr 3, s. 245-254Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Objectives: The matricellular protein osteopontin is involved in the pathogenesis of both kidney and cardiovascular disease. However, whether circulating and urinary osteopontin levels are associated with the risk of these diseases is less studied.

    Design, Setting, Participants, and Measurements: A community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM]; n = 741; mean age: 77 years) was used to study the associations between plasma and urinary osteopontin, incident chronic kidney disease, and the risk of cardiovascular death during a median of 8 years of follow-up.

    Results: There was no significant cross-sectional correlation between plasma and urinary osteopontin (Spearman. = 0.07, p = 0.13). Higher urinary osteopontin, but not plasma osteopontin, was associated with incident chronic kidney disease in multivariable models adjusted for age, cardiovascular risk factors, baseline glomerular filtration rate, urinary albumin/ creatinine ratio, and the inflammatory markers interleukin 6 and high-sensitivity C-reactive protein (odds ratio for 1 standard deviation [SD] of urinary osteopontin, 1.42, 95% CI 1.00-2.02, p = 0.048). Conversely, plasma osteopontin, but not urinary osteopontin, was independently associated with cardiovascular death (multivariable hazard ratio per SD increase, 1.35, 95% CI 1.14-1.58, p < 0.001, and 1.00, 95% CI 0.79-1.26, p = 0.99, respectively). The addition of plasma osteopontin to a model with established cardiovascular risk factors significantly increased the C-statistics for the prediction of cardiovascular death (p < 0.002).

    Conclusions: Higher urinary osteopon-tin specifically predicts incident chronic kidney disease, while plasma osteopontin specifically predicts cardiovascular death. Our data put forward osteopontin as an important factor in the detrimental interplay between the kidney and the cardiovascular system. The clinical implications, and why plasma and urinary osteopontin mirror different pathologies, remain to be established.

  • 105.
    Feldreich, T. Rudholm
    et al.
    Dalarna Univ, Med Sci, Falun, Sweden..
    Carlsson, Axel C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Larsson, A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Higher circulating osteopontin specifically predicts cardiovascular death while urinary osteopontin predicts kidney disease progression2016Ingår i: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, s. 1282-1282Artikel i tidskrift (Refereegranskat)
  • 106.
    Feldreich, T. Rudholm
    et al.
    Dalarna Univ, Med Sci, Falun, Sweden..
    Carlsson, Axel C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Riserus, U
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Larsson, A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    The association between serum cathepsin l and mortality in older adults2016Ingår i: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, s. 1283-1283Artikel i tidskrift (Refereegranskat)
  • 107.
    Feldreich, Tobias
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. School of Health and Social Studies, Dalarna University, Falun, .
    Carlsson, Axel C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. School of Health and Social Studies, Dalarna University, Falun, .
    The association between serum cathepsin L and mortality in older adults2016Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 254, s. 109-116Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND AIMS: Research suggests that the protease cathepsin L is causally involved in atherosclerosis. However, data on cathepsin L as a risk marker are lacking. Therefore, we investigated associations between circulating cathepsin L and cardiovascular mortality.

    METHODS: Two independent community-based cohorts were used: Uppsala Longitudinal Study of Adult Men (ULSAM); n = 776; mean age 77 years; baseline 1997-2001; 185 cardiovascular deaths during 9.7 years follow-up, and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS); n = 993; 50% women; mean age 70 years; baseline 2001-2004; 42 cardiovascular deaths during 10.0 years follow-up.

    RESULTS: Higher serum cathepsin L was associated with an increased risk for cardiovascular mortality in age- and sex-adjusted models in both cohorts (ULSAM: hazard ratio (HR) for 1-standard deviation (SD) increase, 1.17 [95% CI, 1.01-1.34], p = 0.032 PIVUS: HR 1.35 [95% CI, 1.07-1.72], p = 0.013). When merging the cohorts, these associations were independent of inflammatory markers and cardiovascular risk factors, but non-significant adjusting for kidney function. Individuals with a combination of elevated cathepsin L and increased inflammation, kidney dysfunction, or prevalent cardiovascular disease had a markedly increased risk, while no increased risk was associated with elevated cathepsin L, in the absence of these disease states.

    CONCLUSIONS: An association between higher serum cathepsin L and increased risk of cardiovascular mortality was found in two independent cohorts. Impaired kidney function appears to be an important moderator or mediator of these associations. Further studies are needed to delineate the underlying mechanisms and to evaluate whether the measurement of cathepsin L might have clinical utility.

  • 108. Ferreira, Daniel
    et al.
    Hansson, Oskar
    Barroso, José
    Molina, Yaiza
    Machado, Alejandra
    Hernández-Cabrera, Juan Andrés
    Muehlboeck, J-Sebastian
    Stomrud, Erik
    Nägga, Katarina
    Lindberg, Olof
    Ames, David
    Kalpouzos, Grégoria
    Fratiglioni, Laura
    Bäckman, Lars
    Graff, Caroline
    Mecocci, Patrizia
    Vellas, Bruno
    Tsolaki, Magda
    Kłoszewska, Iwona
    Soininen, Hilkka
    Lovestone, Simon
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wahlund, Lars-Olof
    Simmons, Andrew
    Westman, Eric
    The interactive effect of demographic and clinical factors on hippocampal volume: A multicohort study on 1958 cognitively normal individuals2017Ingår i: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 27, nr 6, s. 653-667Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.

  • 109.
    Figarska, Sylwia M.
    et al.
    Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, 300 Pasteur Dr, Stanford, CA 94305 USA.
    Gustafsson, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ärnlöv, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden;Dalarna Univ, Sch Hlth & Social Sci, Falun, Sweden.
    Mälarstig, Anders
    Pfizer Worldwide Res & Dev, Stockholm, Sweden;Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.
    Elmstahl, Sölve
    Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Div Geriatr Med, Lund, Sweden.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, 300 Pasteur Dr, Stanford, CA 94305 USA.
    Associations of Circulating Protein Levels With Lipid Fractions in the General Population2018Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 38, nr 10, s. 2505-2518Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Revealing patterns of associations between circulating protein and lipid levels could improve biological understanding of cardiovascular disease (CVD). In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in individuals from the general population.

    Approach and Results: We measured plasma protein levels using the Olink ProSeek CVD I or II+III arrays and analyzed 57 proteins available in 3 population-based cohorts: EpiHealth (n=2029; 52% women; median age, 61 years), PIVUS (Prospective Study of the Vasculature in Uppsala Seniors; n=790; 51% women; all aged 70 years), and ULSAM (Uppsala Longitudinal Study of Adult Men; n=551; all men aged 77 years). A discovery analysis was performed in EpiHealth in a regression framework (adjusted for sex, age, body mass index, smoking, glucose levels, systolic blood pressure, blood pressure medication, diabetes mellitus medication, and CVD history), and associations with false discovery rate <0.05 were further tested in PIVUS and ULSAM, where a P value of 0.05 was considered a successful replication (validation false discovery rate of 0.1%). We used summary statistics from a genome-wide association study on each protein biomarker (meta-analysis of EpiHealth, PIVUS, ULSAM, and IMPROVE [Carotid Intima-Media Thickness and IMT-Progression as Predictors of Vascular Events in a High-Risk European Population]) and publicly available data from Global Lipids Genetics Consortium to perform Mendelian randomization analyses to address possible causality of protein levels. Of 57 tested proteins, 42 demonstrated an association with at least 1 lipid fraction; 35 were associated with TG, 15 with total cholesterol, 9 with LDL cholesterol, and 24 with HDL cholesterol. Among these associations, we found KIM-1 (kidney injury molecule-1), TNFR (TNF [tumor necrosis factor] receptor) 1 and 2, TRAIL-R2 (TRAIL [TNF-related apoptosis-inducing ligand] receptor 2), and RETN (resistin) to be associated with all 4 lipid fractions. Further, 15 proteins were related to both TG and HDL cholesterol in a consistent and biologically expected manner, that is, higher TG and lower HDL cholesterol or vice versa. Another common pattern of associations was concomitantly higher TG, total cholesterol, and LDL cholesterol, which is associated with higher CVD risk. We did not find evidence of causal links for protein levels.

    Conclusions: Our comprehensive analysis of plasma proteins and lipid fractions of 3370 individuals from the general population provides new information about lipid metabolism.

  • 110. Figtree, G. A.
    et al.
    Kindmark, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Grundberg, Elin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Speller, B.
    Robinson, B.G.
    Channon, K.M.
    Watkins, H.
    Novel estrogen receptor alpha promoter polymorphism increases ventricular hypertrophic response to hypertension2007Ingår i: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 103, nr 2, s. 110-118Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Given the strong genetic contribution to blood pressure and left ventricular hypertrophy (LVH), and the influence of estrogen on these parameters, we hypothesized that polymorphisms in the estrogen receptor alpha (ERα) promoter may influence LVH. Three novel polymorphisms were identified upstream of the ERα alternatively spliced exon 1E, within sequence which demonstrated significant promoter activity in vitro. Demonstration of ERα E isoform expression in human ventricle by RT-PCR supported a possible functional role for the 1E novel polymorphisms in estrogen signaling in the heart. Indeed, G > A (-721 E) was significantly associated with LVH after controlling for systolic blood pressure and sex in a healthy population (n = 74), contributing to 23% of interventricular septum (IVS) width variance (p < 0.001) and 9.4% of left ventricular mass index (LVMI) variance (p = 0.035). In a separate hypertensive cohort, male carriers of the A allele (n = 8) had a 17% increase in IVS (95% CI: 6-28%) and a 19% increase in LVMI (3-34%) compared to GG homozygotes (n = 84). We conclude that a novel polymorphism in the promoter of a cardiac mRNA splice isoform of ERα is associated with LVH.

  • 111.
    Flannick, Jason
    et al.
    Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Fuchsberger, Christian
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Mahajan, Anubha
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Teslovich, Tanya M.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Agarwala, Vineeta
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;MIT, Harvard Div Hlth Sci & Technol, Cambridge, MA USA..
    Gaulton, Kyle J.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Caulkins, Lizz
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Koesterer, Ryan
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Ma, Clement
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Moutsianas, Loukas
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    McCarthy, Davis J.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Rivas, Manuel A.
    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, Univ Exeter Med Sch, Genet Complex Traits, Exeter, Devon, England.;Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.;Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Sim, Xueling
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Blackwell, Thomas W.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 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..
    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, Cambridgeshire, England..
    Cingolani, Pablo
    McGill Univ, Sch Comp Sci, Montreal, PQ, Canada.;McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ H3A 2T5, Canada..
    Locke, Adam E.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Tajes, Juan Fernandez
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Highland, Heather M.
    Univ Texas Grad Sch Biomed Sci, Ctr Human Genet, Univ Texas Hlth Sci Ctr, Houston, TX USA..
    Dupuis, Josee
    Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA.;Boston Univ Sch Publ Hlth, Dept Biostatist, Boston, MA USA.;Nat Heart Lung & Blood Inst Framingham Heart Stud, Framingham, MA USA..
    Chines, Peter S.
    NIH, Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD USA..
    Lindgren, Cecilia M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Hartl, Christopher
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Chen, Han
    Boston Univ Sch Publ Hlth, Dept Biostatist, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Biostatist, Boston, MA USA..
    Huyghe, Jeroen R.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    De Bunt, Martijn Van
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Pearson, Richard D.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Kumar, Ashish
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Basel, Swiss Trop & Publ Hlth Inst, Chron Dis Epidemiol, Basel, Switzerland..
    Muller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Univ Hosp Grosshadern, Ludwig Maximilians Univ, Dept Med I, Munich, Germany.;Ludwig Maximilians Univ Munchen, IBE, Chair Genet Epidemiol, Fac Med, Munich, Germany.;DZHK German Ctr Cardiovascular Res, Munich Heart Alliance, Munich, Germany..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Gamazon, Eric R.
    Univ Chicago, Med Genet Sect, Dept Med, Chicago, IL USA..
    Lee, Jaehoon
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Chen, Yuhui
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Below, Jennifer E.
    Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA..
    Chen, Peng
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Huang, Jinyan
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Go, Min Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbukdo, South Korea..
    Stitzel, Michael L.
    Jackson Lab Genom Med, Farmington, CT USA..
    Pasko, Dorota
    Univ Exeter, Univ Exeter Med Sch, Genet Complex Traits, Exeter, Devon, England..
    Parker, Stephen C. J.
    Univ Michigan, Dept Computat Med Bioinformat, Ann Arbor, MI USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI USA..
    Varga, Tibor V.
    Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden..
    Green, Todd
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Beer, Nicola L.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Day-Williams, Aaron G.
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambridgeshire, England..
    Ferreira, Teresa
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Fingerlin, Tasha
    Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA..
    Horikoshi, Momoko
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Hu, Cheng
    Shanghai Jiao Tong Univ, Shanghai Diabet Inst, Dept Endocrinol & Metab, Sixth Peoples Hosp, Shanghai, Peoples R China..
    Huh, Iksoo
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Ikram, Mohammad Kamran
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Eye Acad Clin Programme, Duke NUS Grad Med Sch, Singapore, Singapore..
    Kim, Bong-Jo
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbukdo, South Korea..
    Kim, Yongkang
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Kim, Young Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbukdo, South Korea..
    Kwon, Min-Seok
    Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Lee, Juyoung
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbukdo, South Korea..
    Lee, Selyeong
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Lin, Keng-Han
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Maxwell, Taylor J.
    Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA..
    Nagai, Yoshihiko
    McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ H3A 2T5, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;Res Inst McGill Univ Hlth Ctr, Montreal, PQ, Canada..
    Wang, Xu
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Welch, Ryan P.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Yoon, Joon
    Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Zhang, Weihua
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Barzilai, Nir
    Albert Einstein Coll Med, Dept Med, New York, NY USA.;Albert Einstein Coll Med, Dept Genet, New York, NY USA..
    Voight, Benjamin F.
    Univ Pennsylvania, Dept Syst Pharmacol & Translat Therapeut, Perelman Sch Med, Philadelphia, PA USA.;Univ Pennsylvania, Dept Genet, Perelman Sch Med, Philadelphia, PA USA..
    Han, Bok-Ghee
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbukdo, South Korea..
    Jenkinson, Christopher P.
    Univ Texas Hlth Sci Ctr, Dept Med, San Antonio, TX USA.;South Texas Vet Hlth Care Syst, Res, San Antonio, TX USA..
    Kuulasmaa, Teemu
    Univ Eastern Finland, Inst Clin Med, Fac Hlth Sci, Internal Med, Kuopio, Finland..
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Fac Hlth Sci, Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Manning, Alisa
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 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..
    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, Dept Biochem, Winston Salem, NC USA..
    Balkau, Beverley
    Inserm U1018, Ctr Res Epidemiol & Populat Hlth, Villejuif, France..
    Stancakova, Alena
    Univ Eastern Finland, Inst Clin Med, Fac Hlth Sci, Internal Med, Kuopio, Finland..
    Abboud, Hanna E.
    Univ Texas Hlth Sci Ctr, Dept Med, San Antonio, TX USA..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany..
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Prabhakaran, Dorairaj
    Ctr Chron Dis Control, New Delhi, India..
    Gottesman, Omri
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA..
    Scott, James
    Natl Heart & Lung Inst, Cardiovascular Sci, Imperial Coll London, Hammersmith Campus, London, England..
    Carey, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Kwan, Phoenix
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Grant, George
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Smith, Joshua D.
    Univ Washington Sch Med, Dept Genome Sci, Seattle, WA USA..
    Neale, Benjamin M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA USA..
    Purcell, Shaun
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Ctr Genom Med, Boston, MA USA.;Icahn Inst Genom & Multiscale Biol, Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA..
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Lee, Heung Man
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China..
    Lu, Yingchang
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA..
    Kwak, Soo-Heon
    Seoul Natl Univ Coll Med, Dept Internal Med, Seoul, South Korea..
    Zhao, Wei
    Univ Pennsylvania, Dept Med, Philadelphia, PA USA..
    Danesh, John
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambridgeshire, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England..
    Lam, Vincent K. L.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China..
    Park, Kyong Soo
    Seoul Natl Univ, Dept Mol Med & Biopharmaceut Sci, Grad Sch Convergence Sci & Technol, Seoul, South Korea.;Seoul Natl Univ, Coll Med, Seoul, South Korea..
    Saleheen, Danish
    Univ Pennsylvania, Dept Biostatist & Epidemiol, Philadelphia, PA USA.;Ctr Non Communicable Dis, Karachi, Pakistan..
    So, Wing Yee
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China..
    Tam, Claudia H. T.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China..
    Afzal, Uzma
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Aguilar, David
    Baylor Coll Med, Cardiovascular Div, Houston, TX USA..
    Arya, Rector
    Univ Texas Hlth Sci Ctr, Dept Pediat, San Antonio, TX USA..
    Aung, Tin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Eye Acad Clin Programme, Duke NUS Grad Med Sch, Singapore, Singapore..
    Chan, Edmund
    Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore..
    Navarro, Carmen
    Murcia Reg Hlth Council, Dept Epidemiol, IMIB Arrixaca, Murcia, Spain.;CIBER Epidemiol Salud Publ CIBERESP, Madrid, Spain.;Univ Murcia, Sch Med, Unit Prevent Med & Publ Hlth, Murcia, Spain..
    Cheng, Ching-Yu
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Eye Acad Clin Programme, Duke NUS Grad Med Sch, Singapore, Singapore..
    Palli, Domenico
    Canc Res & Prevent Inst ISPO, Florence, Italy..
    Correa, Adolfo
    Univ Mississippi Med Ctr, Dept Med, Jackson, MS USA..
    Curran, Joanne E.
    Univ Texas Hlth Sci Ctr, San Antonio Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Rybin, Dennis
    Boston Univ Sch Publ Hlth, Dept Biostatist, Boston, MA USA..
    Farook, Vidya S.
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Fowler, Sharon P.
    Univ Texas Hlth Sci Ctr, Dept Med, San Antonio, TX USA..
    Freedman, Barry I.
    Wake Forest Sch Med, Nephrol Sect, Dept Internal Med, Winston Salem, NC USA..
    Griswold, Michael
    Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA..
    Hale, Daniel Esten
    Univ Texas Hlth Sci Ctr, Dept Pediat, San Antonio, TX USA..
    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, Dept Biochem, Winston Salem, NC USA..
    Khor, Chiea-Chuen
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Dept Paediat, Yong Loo Lin Sch Med, Singapore, Singapore..
    Kumar, Satish
    Univ Texas Hlth Sci Ctr, San Antonio Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Lehne, Benjamin
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Thuillier, Dorothee
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France..
    Lim, Wei Yen
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Liu, Jianjun
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Divis Human Genet, Singapore, Singapore..
    Loh, Marie
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Univ Oulu, Inst Hlth Sci, Oulu, Finland.;ASTAR, Translat Lab Genet Med TLGM, Singapore, Singapore..
    Musani, Solomon K.
    Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39216 USA..
    Puppala, Sobha
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Scott, William R.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Yengo, Loic
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France..
    Tan, Sian-Tsung
    Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Natl Heart & Lung Inst, Cardiovascular Sci, Imperial Coll London, Hammersmith Campus, London, England..
    Taylor, Herman A.
    Univ Mississippi Med Ctr, Dept Med, Jackson, MS USA..
    Thameem, Farook
    Univ Texas Hlth Sci Ctr, Dept Med, San Antonio, TX USA..
    Wilson, Gregory
    Jackson State Univ, Coll Publ Serv, Jackson, MS USA..
    Wong, Tien Yin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Eye Acad Clin Programme, Duke NUS Grad Med Sch, Singapore, Singapore..
    Njolstad, Pal Rasmus
    Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway.;Haukeland Hosp, Dept Pediat, Bergen, Norway..
    Levy, Jonathan C.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.;Guys & St Thomas Fdn Trust, NIHR Biomed Res Ctr, London, England..
    Bonnycastle, Lori L.
    NIH, Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD USA..
    Schwarzmayr, Thomas
    Helmholtz Zentrum Munchen, Inst Human Genet, German Res Ctr Environm Hlth, Neuherberg, Germany..
    Fadista, Joao
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, Malmo, Sweden..
    Surdulescu, Gabriela L.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Herder, Christian
    Heinrich Heine Univ, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD, Munich, Germany..
    Groves, Christopher J.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Wieland, Thomas
    Helmholtz Zentrum Munchen, Inst Human Genet, German Res Ctr Environm Hlth, Neuherberg, Germany..
    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..
    Christensen, Cramer
    Vejle Hosp, Dept Internal Med & Endocrinol, Vejle, Denmark..
    Koistinen, Heikki A.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Helsinki Univ Cent Hosp, Abdominal Ctr Endocrinol, Helsinki, Finland.;Minerva Fdn, Helsinki, Finland.;Univ Helsinki, Dept Med, Helsinki, Finland.;Helsinki Univ Cent Hosp, Dept Med, Helsinki, Finland..
    Doney, Alex S. F.
    Med Res Inst, Ninewells Hosp & Med Sch, Divis Cardiovascular & Diabet Med, Dundee, Scotland..
    Kinnunen, Leena
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Esko, Tonu
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Boston Childrens Hosp, Divis Endocrinol, Boston, MA USA..
    Farmer, Andrew J.
    Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England..
    Hakaste, Liisa
    Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Helsinki Univ Cent Hosp, Abdominal Ctr Endocrinol, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland..
    Hodgkiss, Dylan
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Kravic, Jasmina
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, Malmo, Sweden..
    Lyssenko, Valeriya
    Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway.;Lund Univ, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, Malmo, Sweden..
    Hollensted, Mette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Jorgensen, Marit E.
    Steno Diabet Ctr, Gentofte, Denmark..
    Jorgensen, Torben
    Capital Region Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Univ Copenhagen, Inst Hlth Sci, Dept Publ Hlth, Copenhagen, Denmark.;Aalborg Univ, Fac Med, Aalborg, Denmark..
    Ladenvall, Claes
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, Malmo, Sweden..
    Justesen, Johanne Marie
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Karajamaki, Annemari
    Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland.;Vaasa Hlth Care Ctr, Ctr Diabet, Vaasa, Finland..
    Kriebel, Jennifer
    German Ctr Diabet Res DZD, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol II, Neuherberg, Germany.;Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany..
    Rathmann, Wolfgang
    German Ctr Diabet Res DZD, Munich, Germany.;Heinrich Heine Univ, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Biometr & Epidemiol, Dusseldorf, Germany..
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lauritzen, Torsten
    Aarhus Univ, Sect Gen Practice, Dept Publ Hlth, Aarhus, Denmark..
    Narisu, Narisu
    NIH, Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD USA..
    Linneberg, Allan
    Capital Region Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Dept Clin Expt Res, Rigshospitalet, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Melander, Olle
    Lund Univ, Dept Clin Sci, Hypertens & Cardiovascular Dis, Malmo, Sweden..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    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..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, Diabet & Cardiovascular Dis, Genet Epidemiol, Malmo, Sweden..
    Qi, Lu
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp & Harvard Med Sch, Channing Div Network Med, Dept Med, Boston, MA USA..
    Qi, Qibin
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA..
    Roden, Michael
    Heinrich Heine Univ, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD, Munich, Germany.;Heinrich Heine Univ, Fac Med, Divis Endocrinol & Diabetol, Dusseldorf, Germany..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Swift, Amy
    NIH, Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD USA..
    Rosengren, Anders H.
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, Malmo, Sweden..
    Stirrups, Kathleen
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambridgeshire, England..
    Wood, Andrew R.
    Univ Exeter, Univ Exeter Med Sch, Genet Complex Traits, Exeter, Devon, England..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Blancher, Christine
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, Wellcome Trust Ctr Human Genet, Oxford, England..
    Carneiro, Mauricio O.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Maguire, Jared
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Poplin, Ryan
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Shakir, Khalid
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Fennell, Timothy
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    DePristo, Mark
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    De Angelis, Martin Hrabe
    German Ctr Diabet Res DZD, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Expt Genet, Neuherberg, Germany.;Tech Univ Munich, Ctr Life & Food Sci Weihenstephan, Freising Weihenstephan, Germany..
    Deloukas, Panos
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambridgeshire, England.;Queen Mary Univ London, William Harvey Res Inst, London, England.;Queen Mary Univ London, London Sch Med & Dent, London, England.;King Abdulaziz Univ, Princess Jawhara Brahim Ctr Excellence Res Heredi, Jeddah, Saudi Arabia..
    Gjesing, Anette P.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Jun, Goo
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA.;Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA..
    Nilsson, Peter M.
    Lund Univ, Dept Clin Sci, Malmo, Sweden.;Lund Univ, Dept Med, Malmo, Sweden..
    Murphy, Jacquelyn
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Onofrio, Robert
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Thorand, Barbara
    German Ctr Diabet Res DZD, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol II, Neuherberg, Germany..
    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..
    Meisinger, Christa
    German Ctr Diabet Res DZD, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol II, Neuherberg, Germany..
    Hu, Frank B.
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA..
    Isomaa, Bo
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Social Serv & Hlth Care, Pietarsaari, Finland..
    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..
    Liang, Liming
    Harvard Sch Publ Hlth, Dept Biostatist, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Peters, Annette
    DZHK German Ctr Cardiovascular Res, Munich Heart Alliance, Munich, Germany.;German Ctr Diabet Res DZD, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol II, Neuherberg, Germany..
    Huth, Cornelia
    German Ctr Diabet Res DZD, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol II, Neuherberg, Germany..
    O'Rahilly, Stephen P.
    Univ Cambridge, Inst Metab Sci, Metabol Res Labs, Cambridge, England..
    Palmer, Colin N. A.
    Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogenet, Dundee, Scotland.;Ninewells Hosp & Med Sch, Med Res Inst, Dundee, Scotland..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Foundat Res Hlth Exercise & Nutr, Kuopio, Finland..
    Tuomilehto, Jaakko
    Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;King Abdulaziz Univ, Diabetes Res Grp, Jeddah, Saudi Arabia.;Dasman Diabet Inst, Kuwait, Kuwait.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland..
    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, Diabet & Obes Res Inst, Keck Sch Med, Los Angeles, CA USA..
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bergman, Richard N.
    Cedars Sinai Diabet & Obes Res Inst, Los Angeles, CA USA..
    Bharadwaj, Dwaipayan
    CSIR Inst Genom Integrat Biol CSIR IGIB, Funct Genom Unit, New Delhi, India..
    Bottinger, Erwin P.
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA..
    Cho, Yoon Shin
    Hallym Univ, Dept Biomed Sci, Chunchon, South Korea..
    Chandak, Giriraj R.
    CSIR, Ctr Cellular & Mol Biol, Hyderabad, Andhra Pradesh, India..
    Chan, Juliana Cn
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Peoples R China..
    Chia, Kee Seng
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Daly, Mark J.
    Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA USA..
    Ebrahim, Shah B.
    Ctr Chron Dis Control, New Delhi, India..
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Elliott, Paul
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Jablonski, Kathleen A.
    George Washington Univ, Biostatist Ctr, Rockville, MD USA..
    Lehman, Donna M.
    Univ Texas Hlth Sci Ctr, Dept Med, San Antonio, TX USA..
    Jia, Weiping
    Shanghai Jiao Tong Univ, Shanghai Diabet Inst, Dept Endocrinol & Metab, Sixth Peoples Hosp, Shanghai, Peoples R China..
    Ma, Ronald Cw
    Boston Univ Sch Publ Hlth, Dept Biostatist, Boston, MA USA.;Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Peoples R China..
    Pollin, Toni I.
    Univ Maryland Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD USA.;Univ Maryland Sch Med, Program Personalized Genom Med, Baltimore, MD USA..
    Sandhu, Manjinder
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambridgeshire, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Tandon, Nikhil
    All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi, India..
    Froguel, Philippe
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France.;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambridgeshire, England.;Univ Cambridge, Inst Metab Sci, Metabol Res Labs, Cambridge, England..
    Teo, Yik Ying
    Natl Univ Singapore, Natl Univ Hlth Syst, 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, Cambridgeshire, England..
    Loos, Ruth J. F.
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Ried, Janina S.
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    DeFronzo, Ralph A.
    Univ Texas Hlth Sci Ctr, Dept Med, San Antonio, TX USA..
    Grallert, Harald
    German Ctr Diabet Res DZD, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol II, Neuherberg, Germany.;Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany..
    Glaser, Benjamin
    Hadassah Hebrew Univ Med Ctr, Endocrinol & Metab Serv, Jerusalem, Israel..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Walker, Mark
    Newcastle Univ, Inst Cellular Med, Sch Med, Newcastle Upon Tyne, Tyne & Wear, England..
    Banks, Eric
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Gieger, Christian
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol II, Neuherberg, Germany.;Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
    Im, Hae Kyung
    Univ Chicago, Med Genet Sect, Dept Med, Chicago, IL USA..
    Illig, Thomas
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Hannover, NH, Germany.;Hannover Med Sch, Dept Human Genet, Hannover, NH, Germany..
    Franks, Paul W.
    Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Buck, Gemma
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, Wellcome Trust Ctr Human Genet, Oxford, England..
    Trakalo, Joseph
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, Wellcome Trust Ctr Human Genet, Oxford, England..
    Buck, David
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, Wellcome Trust Ctr Human Genet, Oxford, England..
    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..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Farjoun, Yossi
    Broad Inst, Data Sci & Data Engn, Cambridge, MA USA..
    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..
    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..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, IBE, Chair Genet Epidemiol, Fac Med, Munich, Germany..
    Tuomi, Tiinamaija
    Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Helsinki Univ Cent Hosp, Abdominal Ctr Endocrinol, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    Kooner, Jaspal Singh
    Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Natl Heart & Lung Inst, Cardiovascular Sci, Imperial Coll London, Hammersmith Campus, London, England.;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England..
    Lee, Jong-Young
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbukdo, South Korea..
    Park, Taesung
    Seoul Natl Univ, Dept Stat, Seoul, South Korea.;Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Donnelly, Peter
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Morris, Andrew D.
    Ninewells Hosp & Med Sch, Ctr Mol Med, Clin Res Ctr, Dundee, Scotland.;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Hattersley, Andrew T.
    Univ Exeter, Univ Exeter Med Sch, Exeter, Devon, England..
    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, Dept Biochem, Winston Salem, NC USA..
    Collins, Francis S.
    NIH, Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD 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, Dept Nat Sci, Haifa, Israel..
    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..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Fac Hlth Sci, Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Strom, Tim M.
    Helmholtz Zentrum Munchen, Inst Human Genet, German Res Ctr Environm Hlth, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Bell, Graeme I.
    Univ Chicago, Dept Med, Chicago, IL USA.;Univ Chicago, Dept Human Genet, Chicago, IL USA..
    Blangero, John
    Univ Texas Hlth Sci Ctr, San Antonio Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Duggirala, Ravindranath
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Tai, EShyong
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore.;Duke NUS Med Sch Singapore, Cardiovascular Metab Disorders Program, Singapore, Singapore..
    McVean, Gilean
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England..
    Hanis, Craig L.
    Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA..
    Wilson, James G.
    Univ Mississippi Med Ctr, Dept Physiol & Biophys, Jackson, MS USA..
    Seielstad, Mark
    Univ Calif San Francisco, Dept Lab Med, Inst Human Genet, San Francisco, CA USA.;Blood Syst Res Inst, San Francisco, CA USA..
    Frayling, Timothy M.
    Univ Exeter, Univ Exeter Med Sch, Genet Complex Traits, Exeter, Devon, England..
    Meigs, James B.
    Harvard Med Sch, Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA..
    Cox, Nancy J.
    Univ Chicago, Med Genet Sect, Dept Med, Chicago, IL USA..
    Sladek, Rob
    McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ H3A 2T5, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ, Dept Med, Divis Endocrinol & Metab, Montreal, PQ, Canada..
    Lander, Eric S.
    MIT, Broad Inst, Cambridge, MA USA..
    Gabriel, Stacey
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Meitinger, Thomas
    Helmholtz Zentrum Munchen, Inst Human Genet, German Res Ctr Environm Hlth, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Groop, Leif
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, Malmo, Sweden.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    Abecasis, Goncalo
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Scott, Laura J.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    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..
    Kang, Hyun Min
    Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA..
    Altshuler, David
    Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr Diabet Unit, Boston, MA USA.;MIT, Dept Biol, Cambridge, MA 02139 USA..
    Burtt, Noel P.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Florez, Jose C.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Ctr Genom Med, Boston, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr Diabet Unit, Boston, MA USA..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 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..
    Data Descriptor: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls2017Ingår i: Scientific Data, E-ISSN 2052-4463, Vol. 4, artikel-id 170179Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.

  • 112. Flannick, Jason
    et al.
    Thorleifsson, Gudmar
    Beer, Nicola L.
    Jacobs, Suzanne B. R.
    Grarup, Niels
    Burtt, Noel P.
    Mahajan, Anubha
    Fuchsberger, Christian
    Atzmon, Gil
    Benediktsson, Rafn
    Blangero, John
    Bowden, Don W.
    Brandslund, Ivan
    Brosnan, Julia
    Burslem, Frank
    Chambers, John
    Cho, Yoon Shin
    Christensen, Cramer
    Douglas, Desiree A.
    Duggirala, Ravindranath
    Dymek, Zachary
    Farjoun, Yossi
    Fennell, Timothy
    Fontanillas, Pierre
    Forsen, Tom
    Gabriel, Stacey
    Glaser, Benjamin
    Gudbjartsson, Daniel F.
    Hanis, Craig
    Hansen, Torben
    Hreidarsson, Astradur B.
    Hveem, Kristian
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Isomaa, Bo
    Johansson, Stefan
    Jorgensen, Torben
    Jorgensen, Marit Eika
    Kathiresan, Sekar
    Kong, Augustine
    Kooner, Jaspal
    Kravic, Jasmina
    Laakso, Markku
    Lee, Jong-Young
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindgren, Cecilia M.
    Linneberg, Allan
    Masson, Gisli
    Meitinger, Thomas
    Mohlke, Karen L.
    Molven, Anders
    Morris, Andrew P.
    Potluri, Shobha
    Rauramaa, Rainer
    Ribel-Madsen, Rasmus
    Richard, Ann-Marie
    Rolph, Tim
    Salomaa, Veikko
    Segre, Ayellet V.
    Skaerstrand, Hanna
    Steinthorsdottir, Valgerdur
    Stringham, Heather M.
    Sulem, Patrick
    Tai, E. Shyong
    Teo, Yik Ying
    Teslovich, Tanya
    Thorsteinsdottir, Unnur
    Trimmer, Jeff K.
    Tuomi, Tiinamaija
    Tuomilehto, Jaakko
    Vaziri-Sani, Fariba
    Voight, Benjamin F.
    Wilson, James G.
    Boehnke, Michael
    McCarthy, Mark I.
    Njolstad, Pal R.
    Pedersen, Oluf
    Groop, Leif
    Cox, David R.
    Stefansson, Kari
    Altshuler, David
    Loss-of-function mutations in SLC30A8 protect against type 2 diabetes2014Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, nr 4, s. 357-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets1-3, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of -150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) 4 and harbors a common variant (p. Trp325Arg) associated with T2D risk and glucose and proinsulin levels5-7. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 x 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p. Lys34Serfs* 50) demonstrated reduced glucose levels (-0.17 s. d., P = 4.6 x 10(-4)). The two most common proteintruncating variants (p. Arg138* and p. Lys34Serfs* 50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk(8,9), and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts(10-15). In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.

  • 113. Folkersen, Lasse
    et al.
    Fauman, Eric
    Sabater-Lleal, Maria
    Strawbridge, Rona J
    Frånberg, Mattias
    Sennblad, Bengt
    Baldassarre, Damiano
    Veglia, Fabrizio
    Humphries, Steve E
    Rauramaa, Rainer
    de Faire, Ulf
    Smit, Andries J
    Giral, Philippe
    Kurl, Sudhir
    Mannarino, Elmo
    Enroth, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Johansson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bosdotter Enroth, Sofia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Lindgren, Cecilia
    Morris, Andrew P
    Giedraitis, Vilmantas
    Silveira, Angela
    Franco-Cereceda, Anders
    Tremoli, Elena
    Gyllensten, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Brunak, Søren
    Eriksson, Per
    Ziemek, Daniel
    Hamsten, Anders
    Mälarstig, Anders
    Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease2017Ingår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, nr 4, artikel-id e1006706Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We identified 79 genome-wide significant (p<5e-8) association signals, 55 of which replicated at P<0.0007 in separate validation studies (n = 2,639 individuals). Using automated text mining, manual curation, and network-based methods incorporating information on expression quantitative trait loci (eQTL), we propose plausible causal mechanisms for 25 trans-acting loci, including a potential post-translational regulation of stem cell factor by matrix metalloproteinase 9 and receptor-ligand pairs such as RANK-RANK ligand. Using public GWA study data, we further evaluate all 79 loci for their causal effect on coronary artery disease, and highlight several potentially causal associations. Overall, a majority of the plasma proteins studied showed evidence of regulation at the genetic level. Our results enable future studies of the causal architecture of human disease, which in turn should aid discovery of new drug targets.

  • 114.
    Forsberg, Lars A.
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala Univ, Beijer Lab Genome Res, Uppsala, Sweden.
    Halvardson, Jonatan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Rychlicka-Buniowska, Edyta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Danielsson, Marcus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Moghadam, Behrooz Torabi
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Mattisson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Rasi, Chiara
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Davies, Hanna
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Lind, Lars
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Dumanski, Jan P.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Med Univ Gdansk, Fac Pharm, Gdansk, Poland.
    Mosaic loss of chromosome Y in leukocytes matters2019Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 1, s. 4-7Artikel i tidskrift (Övrigt vetenskapligt)
  • 115.
    Forsberg, Lars A.
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Rasi, Chiara
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Malmqvist, Niklas
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Davies, Hanna
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Pasupulati, Saichand
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Pakalapati, Geeta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sandgren, Johanna
    de Stahl, Teresita Diaz
    Zaghlool, Ammar
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Score, Joannah
    Cross, Nicholas C. P.
    Absher, Devin
    Tiensuu Janson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Lindgren, Cecilia M.
    Morris, Andrew P.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Dumanski, Jan P.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer2014Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, nr 6, s. 624-628Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Incidence and mortality for sex-unspecific cancers are higher among men, a fact that is largely unexplained(1,2). Furthermore, age-related loss of chromosome Y (LOY) is frequent in normal hematopoietic cells(3,4), but the phenotypic consequences of LOY have been elusive(5-10). From analysis of 1,153 elderly men, we report that LOY in peripheral blood was associated with risks of all-cause mortality (hazards ratio (HR) = 1.91, 95% confidence interval (CI) = 1.17-3.13; 637 events) and non-hematological cancer mortality (HR = 3.62, 95% CI = 1.56-8.41; 132 events). LOY affected at least 8.2% of the subjects in this cohort, and median survival times among men with LOY were 5.5 years shorter. Association of LOY with risk of all-cause mortality was validated in an independent cohort (HR = 3.66) in which 20.5% of subjects showed LOY. These results illustrate the impact of post-zygotic mosaicism on disease risk, could explain why males are more frequently affected by cancer and suggest that chromosome Y is important in processes beyond sex determination. LOY in blood could become a predictive biomarker of male carcinogenesis.

  • 116.
    Fox, Glen A
    et al.
    Canadian Wildlife Service, National Wildlife Research Centre, Carleton University, Ottawa, Ontario, Canada.
    Lundberg, Rebecca
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wejheden, Carolina
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Örberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Ekotoxikologi.
    Lind, Monica
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Health of herring gulls (Larus argentatus) in relation to breeding location in the early 1990s: III. Effects on the bone tissue2008Ingår i: Journal of Toxicology and Environmental Health, ISSN 1528-7394, E-ISSN 1087-2620, Vol. 71, nr 21, s. 1448-1456Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Health effects associated with the Great Lakes environment were assessed in adult herring gulls (Larus argentatus) in the early 1990s, including the size and quality of their bones. Femurs were excised from 140 individuals from 10 colonies distributed throughout the Great Lakes and 2 reference colonies in Lake Winnipeg (freshwater) and the Bay of Fundy (marine). Femurs of gulls from the Great Lakes differed from the freshwater or marine reference for 9 of 12 variables of size, composition, and strength assessed using peripheral quantitative computed tomography (pQCT) and biomechanical testing. Femurs of Great Lakes gulls were significantly smaller in length (-2.9%), periosteal circumference (-2.4%), and cross-sectional area (-5.4%) than freshwater reference birds. Femurs of the Great Lakes gulls had a lower significant cortical bone mineral content (-8.1%) and density (-2%) than the marine reference. A significant increase in the amount the bone could bend before it broke (+34%) and the energy required to break it (+44%) and a significant decrease (-16.3%) in stiffness during three-point biomechanical bending test were also detected in Great Lakes versus the freshwater gulls. These differences are indicative of impaired mineralization. When divided into high and low 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalent (TCDD-TEQ) colonies, the amount the bone could bend before it broke and the energy required to break it were significantly higher in the high TEQ colonies, but not high polychlorinated biphenyl (PCB) colonies. Breeding location and dietary choices of Great Lakes herring gulls in the early 1990s resulted in modulations of physiological processes that affected the size, mineralization, and biomechanical properties of bone.

  • 117.
    Franceschini, Nora
    et al.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27516 USA.
    Giambartolomei, Claudia
    Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
    de Vries, Paul S.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Houston, TX 77030 USA.
    Finan, Chris
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
    Huntley, Rachael P.
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Lovering, Ruth C.
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Tajuddin, Salman M.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Winkler, Thomas W.
    Univ Regensburg, Dept Genet Epidemiol, D-93053 Regensburg, Germany.
    Graff, Misa
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27516 USA.
    Kavousi, Maryam
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands.
    Dale, Caroline
    UCL, Inst Hlth Informat, London WC1E 6BT, England.
    Smith, Albert V.
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland;Univ Iceland, IS-101 Reykjavik, Iceland.
    Hofer, Edith
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, A-8036 Graz, Austria;Med Univ Graz, Inst Med Informat Stat & Documentat, A-8036 Graz, Austria.
    van Leeuwen, Elisabeth M.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands.
    Nolte, Ilja M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-3015 Groningen, Netherlands.
    Lu, Lingyi
    Wake Forest Univ, Bowman Gray Sch Med, Dept Biostatist Sci, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA.
    Scholz, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany.
    Sargurupremraj, Muralidharan
    Univ Bordeaux, INSERM, CHU Bordeaux, Bordeaux Populat Hlth Res Ctr,UMR 1219, F-33000 Bordeaux, France.
    Pitkanen, Niina
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland.
    Franzen, Oscar
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Clin Gene Networks AB, S-10462 Stockholm, Sweden.
    Joshi, Peter K.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
    Noordam, Raymond
    Leiden Univ, Med Ctr, Sect Gerontol & Geriatr, Dept Internal Med, NL-2300 RC Leiden, Netherlands.
    Marioni, Riccardo E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH4 2XU, Midlothian, Scotland.
    Hwang, Shih-Jen
    NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Framingham, MA 01702 USA;NHLBI, Intramural Res Program, Framingham Heart Study, Framingham, MA 01702 USA.
    Musani, Solomon K.
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
    Schminke, Ulf
    Univ Med Greifswald, Dept Neurol, D-17475 Greifswald, Germany.
    Palmas, Walter
    Columbia Univ, Dept Med, New York, NY 10032 USA.
    Isaacs, Aaron
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Maastricht Univ, CARIM Sch Cardiovasc Dis, Maastricht Ctr Syst Biol MaCSBio, Dept Biochem, NL-6229 Maastricht, Netherlands.
    Correa, Adolfo
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
    Zonderman, Alan B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.
    Cox, Amanda J.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 25157 USA;Griffith Univ, Menzies Hlth Inst Queensland, Southport, Qld 4222, Australia.
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus Med Ctr, Dept Internal Med, NL-3015 Rotterdam, Netherlands.
    Wong, Andrew
    UCL, MRC Unit Lifelong Hlth & Ageing, London WC1E 6BT, England.
    Smit, Andries J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Med, NL-2300 Groningen, Netherlands.
    Newman, Anne B.
    Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA;Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA 15213 USA.
    Britton, Annie
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.
    Ruusalepp, Arno
    Clin Gene Networks AB, S-10462 Stockholm, Sweden;Univ Tartu, Inst Biomed & Translat Med, Dept Pathophysiol, EE-51010 Tartu, Estonia;Tartu Univ Hosp, Dept Cardiac Surg, EE-51010 Tartu, Estonia.
    Sennblad, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17177 Stockholm, Sweden.
    Hedblad, Bo
    Lund Univ, Dept Clin Sci Malmo, SE-20502 Malmo, Sweden.
    Pasaniuc, Bogdan
    Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA;Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
    Penninx, Brenda W.
    Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res & Neurosci Campus Amste, Department Psychiat, NL-1081 HL Amsterdam, Netherlands.
    Langefeld, Carl D.
    Wake Forest Univ, Bowman Gray Sch Med, Dept Biostatist Sci, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA.
    Wassel, Christina L.
    Premier Inc, Appl Sci, Charlotte, NC 28277 USA.
    Tzourio, Christophe
    Univ Bordeaux, INSERM, CHU Bordeaux, Bordeaux Populat Hlth Res Ctr,UMR 1219, F-33000 Bordeaux, France.
    Fava, Cristiano
    Lund Univ, Dept Clin Sci Malmo, SE-20502 Malmo, Sweden;Univ Verona, Dept Med, I-37134 Verona, Italy.
    Baldassarre, Damiano
    Univ Milan, Dept Med Biotechnol & Translat Med, I-20133 Milan, Italy;IRCCS, Ctr Cardiol Monzino, I-20138 Milan, Italy.
    O'Leary, Daniel H.
    Tufts Univ, Sch Med, St Elizabeths Med Ctr, Boston, MA 02135 USA.
    Teupser, Daniel
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany;LMU, Univ Hosp Munich, Inst Lab Med, D-80539 Munich, Germany.
    Kuh, Diana
    UCL, MRC Unit Lifelong Hlth & Ageing, London WC1E 6BT, England.
    Tremoli, Elena
    IRCCS, Ctr Cardiol Monzino, I-20138 Milan, Italy;Univ Milan, Dipartimento Sci Farmacol Biomol, I-20133 Milan, Italy.
    Mannarino, Elmo
    Univ Perugia, Internal Med Angiol & Arteriosclerosis Dis, Dept Clin & Expt Med, I-06123 Perugia, Italy.
    Grossi, Enzo
    Ctr Diagnost Italiano, I-20147 Milan, Italy.
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Houston, TX 77030 USA;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
    Schadt, Eric E.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Clin Gene Networks AB, S-10462 Stockholm, Sweden.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94309 USA;Stanford Univ, Stanford Cardiovasc Inst, G1120, Stanford, CA USA.
    Veglia, Fabrizio
    IRCCS, Ctr Cardiol Monzino, I-20138 Milan, Italy.
    Rivadeneira, Fernando
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus Med Ctr, Dept Internal Med, NL-3015 Rotterdam, Netherlands.
    Beutner, Frank
    Heart Ctr Leipzig, D-04103 Leipzig, Germany.
    Chauhan, Ganesh
    Univ Bordeaux, INSERM, CHU Bordeaux, Bordeaux Populat Hlth Res Ctr,UMR 1219, F-33000 Bordeaux, France;Indian Inst Sci, Ctr Brain Res, Bangalore 560012, Karnataka, India.
    Heiss, Gerardo
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27516 USA.
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-3015 Groningen, Netherlands.
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
    Voelzke, Henry
    Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.
    Markus, Hugh S.
    Univ Cambridge, Dept Clin Neurosci, Stroke Res Grp, Cambridge CB2 0QQ, England.
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands.
    de Graaf, Jacqueline
    Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands.
    Price, Jacqueline
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
    Pott, Janne
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany.
    Hopewell, Jemma C.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford OX3 7LF, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford OX3 7LF, England.
    Liang, Jingjing
    Case Western Reserve Univ, Sch Med, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA.
    Thiery, Joachim
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany;Univ Leipzig, Inst Lab Med, D-04109 Leipzig, Germany.
    Engmann, Jorgen
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Gertow, Karl
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17177 Stockholm, Sweden.
    Rice, Kenneth
    Univ Washington, Dept Biostat, Seattle, WA 98105 USA.
    Taylor, Kent D.
    Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Dhana, Klodian
    Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA.
    Kiemeney, Lambertus A. L. M.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6525 GA Nijmegen, Netherlands.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Raffield, Laura M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27516 USA.
    Launer, Lenore J.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Holdt, Lesca M.
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany;LMU, Univ Hosp Munich, Inst Lab Med, D-80539 Munich, Germany.
    Doer, Marcus
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany;Univ Med Greifswald, Dept Internal Med B, D-17475 Greifswald, Germany.
    Dichgans, Martin
    LMU, Univ Hosp, Inst Stroke & Dementia Res ISD, D-80539 Munich, Germany;Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany.
    Traylor, Matthew
    Univ Cambridge, Dept Clin Neurosci, Stroke Res Grp, Cambridge CB2 0QQ, England.
    Sitzer, Matthias
    Goethe Univ Frankfurt, Ctr Neurol & Neurosurg, Dept Neurol, D-60323 Frankfurt, Germany.
    Kumari, Meena
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England;Essex Univ, Inst Social & Econ Res, Colchester CO4 3SQ, Essex, England.
    Kivimaki, Mika
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.
    Nalls, Mike A.
    NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA;Data Tecn Int, Glen Echo, MD 20812 USA.
    Melander, Olle
    Lund Univ, Dept Clin Sci Malmo, SE-20502 Malmo, Sweden.
    Raitakari, Olli
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland;Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Bern, ISPM, CH-3012 Bern, Switzerland.
    Rueda-Ochoa, Oscar L.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Ind Santander, Sch Med, Electrocardiog Res Grp, Santander 680003, Colombia.
    Roussos, Panos
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA;James J Peters VA Med Ctr, MIRECC, Bronx, NY 10468 USA.
    Whincup, Peter H.
    St Georges Univ London, Populat Hlth Res Inst, London SW17 0RE, England.
    Amouyel, Philippe
    INSERM, U1167, F-59000 Lille, France;Inst Pasteur, U1167, F-59000 Lille, France;Univ Lille, U1167, RID AGE, F-59000 Lille, France;CHU Lille, U1167, F-59000 Lille, France.
    Giral, Philippe
    Sorbonne Univ, Pitie Salpetriere Hosp, Cardiovasc Prevent Unit, F-75013 Paris, France.
    Anugu, Pramod
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
    Wong, Quenna
    Univ Washington, Dept Biostat, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
    Malik, Rainer
    LMU, Univ Hosp, Inst Stroke & Dementia Res ISD, D-80539 Munich, Germany.
    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.
    Burkhardt, Ralph
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany;Univ Leipzig, Inst Lab Med, D-04109 Leipzig, Germany;Univ Hosp Regensburg, Inst Clin Chem & Lab Med, D-93053 Regensburg, Germany.
    Hardy, Rebecca
    UCL, MRC Unit Lifelong Hlth & Ageing, London WC1E 6BT, England.
    Schmidt, Reinhold
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, A-8036 Graz, Austria.
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 Leiden, Netherlands.
    Morris, Richard W.
    Univ Bristol, Bristol Med Sch, Dept Populat Hlth Sci, Bristol BS8 1QU, Avon, England.
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17177 Stockholm, Sweden;Univ Glasgow, Inst Hlth & Wellbeing, Mental Hlth & Wellbeing, Glasgow G12 0XH, Lanark, Scotland.
    Wannamethee, S. Goya
    UCL, Dept Primary Care & Populat Hlth, London WC1E 6BT, England.
    Hagg, Sara
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
    Shah, Sonia
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    McLachlan, Stela
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
    Trompet, Stella
    Leiden Univ, Med Ctr, Sect Gerontol & Geriatr, Dept Internal Med, NL-2300 RC Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands.
    Seshadri, Sudha
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
    Kurl, Sudhir
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, FI-70210 Kuopio, Finland.
    Heckbert, Susan R.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA 98101 USA.
    Ring, Susan
    Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol BS8 1QU, Avon, England;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 1TH, Avon, England.
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33014, Finland;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland.
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6525 GA Nijmegen, Netherlands.
    Shah, Tina
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-17177 Stockholm, Sweden;Karolinska Univ Hosp, Dept Cardiol, S-17177 Stockholm, Sweden.
    Plagnol, Vincent
    UCL, Genet Inst, London WC1E 6BT, England.
    Rosamond, Wayne D.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27516 USA.
    Post, Wendy
    Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA;Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA.
    Zhu, Xiaofeng
    Case Western Reserve Univ, Sch Med, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA.
    Zhang, Xiaoling
    NHLBI, Intramural Res Program, Framingham Heart Study, Framingham, MA 01702 USA;Boston Univ, Sch Med, Sect Biomed Genet, Boston, MA 02215 USA.
    Guo, Xiuqing
    Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA;Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Dept Pediat, Med Ctr, Torrance, CA 90502 USA.
    Saba, Yasaman
    Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, A-8010 Graz, Austria.
    Dehghan, Abbas
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Imperial Coll London, Dept Epidemiol & Biostat, London SW7 2AZ, England.
    Seldenrijk, Adrie
    Univ Amsterdam, Med Ctr, Dept Psychiat, GGZ inGeest & Amsterdam Publ Hlth Res Inst, NL-1081 HV Amsterdam, Netherlands.
    Morrison, Alanna C.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Houston, TX 77030 USA.
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17177 Stockholm, Sweden.
    Psaty, Bruce M.
    Kaiser Permanente Washington Hlth Res Inst, Seattle, WA 98101 USA;Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA;Univ Washington, Dept Med, Seattle, WA 98195 USA;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford OX3 7LF, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford OX3 7LF, England.
    Lawlor, Deborah A.
    Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol BS8 1QU, Avon, England;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 1TH, Avon, England.
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2333 ZA Leiden, Netherlands.
    Bowden, Donald W.
    Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Gen, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA.
    Schmidt, Helena
    Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, A-8010 Graz, Austria.
    Wilson, James F.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland;Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Rotter, Jerome I.
    Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA;Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Dept Pediat, Med Ctr, Torrance, CA 90502 USA.
    Wardlaw, Joanna M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland;Univ Edinburgh, UK Dementia Res Inst, Edinburgh EH16 4SB, Midlothian, Scotland.
    Deanfield, John
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Halcox, Julian
    Swansea Univ, Med Sch, Swansea SA2 8PP, W Glam, Wales.
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33014, Finland;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland.
    Loeffler, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany.
    Evans, Michele K.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Debette, Stephanie
    Univ Bordeaux, INSERM, CHU Bordeaux, Bordeaux Populat Hlth Res Ctr,UMR 1219, F-33000 Bordeaux, France.
    Humphries, Steve E.
    UCL, Inst Cardiovasc Sci, Crt Cardiovasc Genet, London WC1E 6BT, England.
    Voelker, Uwe
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany;Univ Med Greifswald, Interfac Inst Genet & Funct Gen, D-17475 Greifswald, Germany.
    Gudnason, Vilmundur
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland;Univ Iceland, IS-101 Reykjavik, Iceland.
    Hingorani, Aroon D.
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Bjorkegren, Johan L. M.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Clin Gene Networks AB, S-10462 Stockholm, Sweden;Univ Tartu, Inst Biomed & Translat Med, Dept Pathophysiol, EE-51010 Tartu, Estonia;Karolinska Univ Sjukhuset, Karolinska Inst, Dept Med, Integrated Cardio Metab Ctr, SE-14157 Huddinge, Sweden.
    Casas, Juan P.
    UCL, Inst Hlth Informat, London WC1E 6BT, England.
    O'Donnell, Christopher J.
    NHLBI, Intramural Adm Management Branch, NIH, Bldg 10, Bethesda, MD 20892 USA;Boston Vet Adm Healthcare, Cardiol Sect, Boston, MA 02130 USA;Harvard Med Sch, Boston, MA 02115 USA.
    GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes2018Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, artikel-id 5141Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

  • 118.
    Franklin, Stanley S.
    et al.
    Univ Calif Irvine, Sch Med, Div Cardiol, Heart Dis Prevent Program, Irvine, CA 92717 USA..
    Thijs, Lutgarde
    Katholieke Univ Leuven, Dept Cardiovasc Sci, Res Unit Hypertens & Cardiovasc Epidemiol, Studies Coordinating Ctr, Leuven, Belgium..
    Asayama, Kei
    Tohoku Univ, Grad Sch Pharmaceut Sci, Sendai, Miyagi, Japan.;Teikyo Univ, Sch Med, Dept Hyg & Publ Hlth, Tokyo, Japan..
    Li, Yan
    Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Ctr Epidemiol Studies & Clin Trials, Shanghai, Peoples R China.;Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Ctr Vasc Evaluat, Shanghai, Peoples R China..
    Hansen, Tine W.
    Gentofte & Res Ctr Prevent & Hlth, Steno Diabet Ctr, Gentofte, Denmark..
    Boggia, Jose
    Univ Republica, Hosp Clin, Ctr Nefrol, Montevideo, Uruguay.;Univ Republica, Hosp Clin, Dept Fisiopatol, Montevideo, Uruguay..
    Jacobs, Lotte
    Katholieke Univ Leuven, Dept Cardiovasc Sci, Res Unit Hypertens & Cardiovasc Epidemiol, Studies Coordinating Ctr, Leuven, Belgium..
    Zhang, Zhenyu
    Katholieke Univ Leuven, Dept Cardiovasc Sci, Res Unit Hypertens & Cardiovasc Epidemiol, Studies Coordinating Ctr, Leuven, Belgium..
    Kikuya, Masahiro
    Tohoku Univ, Grad Sch Pharmaceut Sci & Med, Sendai, Miyagi, Japan..
    Björklund-Bodegård, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Karolinska Inst, Danderyd Hosp, Dept Cardiol, Stockholm, Sweden..
    Ohkubo, Takayoshi
    Tohoku Univ, Grad Sch Pharmaceut Sci, Sendai, Miyagi, Japan.;Tohoku Univ, Grad Sch Pharmaceut Sci & Med, Sendai, Miyagi, Japan..
    Yang, Wen-Yi
    Katholieke Univ Leuven, Dept Cardiovasc Sci, Res Unit Hypertens & Cardiovasc Epidemiol, Studies Coordinating Ctr, Leuven, Belgium..
    Jeppesen, Jorgen
    Univ Copenhagen, Glostrup Hosp, Dept Med, Copenhagen, Denmark..
    Dolan, Eamon
    Addenbrooks Hosp, Cambridge Univ Hosp, Cambridge, England..
    Kuznetsova, Tatiana
    Inst Internal Med, Novosibirsk, Russia..
    Stolarz-Skrzypek, Katarzyna
    Jagiellonian Univ, Coll Med, Dept Cardiol Intervent Elect & Hypertens 1, Krakow, Poland..
    Tikhonoff, Valerie
    Univ Padua, Dept Med, Padua, Italy..
    Malyutina, Sofia
    Inst Internal Med, Novosibirsk, Russia..
    Casiglia, Edoardo
    Univ Padua, Dept Med, Padua, Italy..
    Nikitin, Yuri
    Inst Internal Med, Novosibirsk, Russia..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sandoya, Edgardo
    Asociac Espanola Primera Socorros Mutuos, Montevideo, Uruguay..
    Kawecka-Jaszcz, Kalina
    Jagiellonian Univ, Coll Med, Dept Cardiol Intervent Elect & Hypertens 1, Krakow, Poland..
    Filipovsky, Jan
    Charles Univ Prague, Fac Med, Plzen, Czech Republic..
    Imai, Yutaka
    Tohoku Univ, Grad Sch Pharmaceut Sci, Sendai, Miyagi, Japan.;Univ Republica, Hosp Clin, Ctr Nefrol, Montevideo, Uruguay.;Univ Republica, Hosp Clin, Dept Fisiopatol, Montevideo, Uruguay..
    Wang, Ji-Guang
    Tohoku Univ, Grad Sch Pharmaceut Sci, Sendai, Miyagi, Japan..
    O'Brien, Eoin
    Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin, Ireland..
    Staessen, Jan A.
    Katholieke Univ Leuven, Dept Cardiovasc Sci, Res Unit Hypertens & Cardiovasc Epidemiol, Studies Coordinating Ctr, Leuven, Belgium.;Maastricht Univ, Dept Epidemiol, Maastricht, Netherlands..
    The Cardiovascular Risk of White-Coat Hypertension2016Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 68, nr 19, s. 2033-2043Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND The role of white-coat hypertension (WCH) and the white-coat-effect (WCE) in development of cardiovascular disease (CVD) risk remains poorly understood. OBJECTIVES Using data from the population-based, 11-cohort IDACO (International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes), this study compared daytime ambulatory blood pressure monitoring with conventional blood pressure measurements in 653 untreated subjects with WCH and 653 normotensive control subjects. METHODS European Society Hypertension guidelines were used as a 5-stage risk score. Low risk was defined as 0 to 2 risk factors, and high risk was defined as >= 3 to 5 risk factors, diabetes, and/or history of prior CVD events. Age-and cohort-matching was done between 653 untreated subjects with WCH and 653 normotensive control subjects. RESULTS In a stepwise linear regression model, systolic WCE increased by 3.8 mm Hg (95% confidence interval [CI]: 3.1 to 4.6 mm Hg) per 10-year increase in age, and was similar in low-and high-risk subjects with or without prior CVD events. Over a median 10.6-year follow-up, incidence of new CVD events was higher in 159 high-risk subjects with WCH compared with 159 cohort-and age-matched high-risk normotensive subjects (adjusted hazard ratio [HR]: 2.06; 95% CI: 1.10 to 3.84; p = 0.023). The HR was not significant for 494 participants with low-risk WCH and age-matched low-risk normotensive subjects. Subgroup analysis by age showed that an association between WCH and incident CVD events is limited to older (age >= 60 years) high-risk WCH subjects; the adjusted HR was 2.19 (95% CI: 1.09 to 4.37; p = 0.027) in the older high-risk group and 0.88 (95% CI: 0.51 to 1.53; p = 0.66) in the older low-risk group (p for interaction = 0.044). CONCLUSIONS WCE size is related to aging, not to CVD risk. CVD risk in most persons with WCH is comparable to age-and risk-adjusted normotensive control subjects.

  • 119. Franklin, Stanley S.
    et al.
    Thijs, Lutgarde
    Hansen, Tine W.
    Li, Yan
    Boggia, Jose
    Kikuya, Masahiro
    Björklund-Bodegård, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ohkubo, Takayoshi
    Jeppesen, Jorgen
    Torp-Pedersen, Christian
    Dolan, Eamon
    Kuznetsova, Tatiana
    Stolarz-Skrzypek, Katarzyna
    Tikhonoff, Valerie
    Malyutina, Sofia
    Casiglia, Edoardo
    Nikitin, Yuri
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sandoya, Edgardo
    Kawecka-Jaszcz, Kalina
    Imai, Yutaka
    Wang, Jiguang
    Ibsen, Hans
    O'Brien, Eoin
    Staessen, Jan A.
    Significance of White-Coat Hypertension in Older Persons With Isolated Systolic Hypertension: A Meta-Analysis Using the International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes Population2012Ingår i: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 59, nr 3, s. 564-571Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The significance of white-coat hypertension in older persons with isolated systolic hypertension remains poorly understood. We analyzed subjects from the population-based 11-country International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes database who had daytime ambulatory blood pressure (BP; ABP) and conventional BP (CBP) measurements. After excluding persons with diastolic hypertension by CBP (>= 90 mm Hg) or by daytime ABP (>= 85 mm Hg), a history of cardiovascular disease, and persons<18 years of age, the present analysis totaled 7295 persons, of whom 1593 had isolated systolic hypertension. During a median follow-up of 10.6 years, there was a total of 655 fatal and nonfatal cardiovascular events. The analyses were stratified by treatment status. In untreated subjects, those with white-coat hypertension (CBP >= 140/<90 mm Hg and ABP<135/<85 mm Hg) and subjects with normal BP (CBP<140/<90 mm Hg and ABP<135/<85 mm Hg) were at similar risk (adjusted hazard rate: 1.17 [95% CI: 0.87-1.57]; P=0.29). Furthermore, in treated subjects with isolated systolic hypertension, the cardiovascular risk was similar in elevated conventional and normal daytime systolic BP as compared with those with normal conventional and normal daytime BPs (adjusted hazard rate: 1.10 [95% CI: 0.79-1.53]; P = 0.57). However, both treated isolated systolic hypertension subjects with white-coat hypertension (adjusted hazard rate: 2.00; [95% CI: 1.43-2.79]; P<0.0001) and treated subjects with normal BP (adjusted hazard rate: 1.98 [95% CI: 1.49-2.62]; P<0.0001) were at higher risk as compared with untreated normotensive subjects. In conclusion, subjects with sustained hypertension who have their ABP normalized on antihypertensive therapy but with residual white-coat effect by CBP measurement have an entity that we have termed, "treated normalized hypertension." Therefore, one should be cautious in applying the term "white-coat hypertension" to persons receiving antihypertensive treatment.

  • 120. Franklin, Stanley S.
    et al.
    Thijs, Lutgarde
    Li, Yan
    Hansen, Tine W.
    Boggia, Jose
    Liu, Yanping
    Asayama, Kei
    Björklund-Bodegard, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ohkubo, Takayoshi
    Jeppesen, Jorgen
    Torp-Pedersen, Christian
    Dolan, Eamon
    Kuznetsova, Tatiana
    Stolarz-Skrzypek, Katarzyna
    Tikhonoff, Valerie
    Malyutina, Sofia
    Casiglia, Edoardo
    Nikitin, Yuri
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Sandoya, Edgardo
    Kawecka-Jaszcz, Kalina
    Filipovsky, Jan
    Imai, Yutaka
    Wang, Jiguang
    Ibsen, Hans
    O'Brien, Eoin
    Staessen, Jan A.
    Masked Hypertension in Diabetes Mellitus Treatment Implications for Clinical Practice2013Ingår i: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 61, nr 5, s. 964-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although distinguishing features of masked hypertension in diabetics are well known, the significance of antihypertensive treatment on clinical practice decisions has not been fully explored. We analyzed 9691 subjects from the population-based 11-country International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes. Prevalence of masked hypertension in untreated normotensive participants was higher (P<0.0001) among 229 diabetics (29.3%, n=67) than among 5486 nondiabetics (18.8%, n=1031). Over a median of 11.0 years of follow-up, the adjusted risk for a composite cardiovascular end point in untreated diabetic-masked hypertensives tended to be higher than in normotensives (hazard rate [HR], 1.96; 95% confidence interval [CI], 0.97-3.97; P=0.059), similar to untreated stage 1 hypertensives (HR, 1.07; CI, 0.58-1.98; P=0.82), but less than stage 2 hypertensives (HR, 0.53; CI, 0.29-0.99; P=0.048). In contrast, cardiovascular risk was not significantly different in antihypertensive-treated diabetic-masked hypertensives, as compared with the normotensive comparator group (HR, 1.13; CI, 0.54-2.35; P=0.75), stage 1 hypertensives (HR, 0.91; CI, 0.49-1.69; P=0.76), and stage 2 hypertensives (HR, 0.65; CI, 0.35-1.20; P=0.17). In the untreated diabetic-masked hypertensive population, mean conventional systolic/diastolic blood pressure was 129.2 +/- 8.0/76.0 +/- 7.3 mm Hg, and mean daytime systolic/diastolic blood pressure 141.5 +/- 9.1/83.7 +/- 6.5 mm Hg. In conclusion, masked hypertension occurred in 29% of untreated diabetics, had comparable cardiovascular risk as stage 1 hypertension, and would require considerable reduction in conventional blood pressure to reach daytime ambulatory treatment goal. Importantly, many hypertensive diabetics when receiving antihypertensive therapy can present with normalized conventional and elevated ambulatory blood pressure that mimics masked hypertension.

  • 121. Franklin, Stanley S.
    et al.
    Thijs, Lutgarde
    Li, Yan
    Hansen, Tine W.
    Boggia, Jose
    Liu, Yanping
    Asayama, Kei
    Björklund-Bodegård, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ohkubo, Takayoshi
    Jeppesen, Jorgen
    Torp-Pedersen, Christian
    Dolan, Eamon
    Kuznetsova, Tatiana
    Stolarz-Skrzypek, Katarzyna
    Tikhonoff, Valerie
    Malyutina, Sofia
    Casiglia, Edoardo
    Nikitin, Yuri
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Sandoya, Edgardo
    Kawecka-Jaszcz, Kalina
    Filipovsky, Jan
    Imai, Yutaka
    Wang, Jiguang
    Ibsen, Hans
    O'Brien, Eoin
    Staessen, Jan A.
    Response to Masked Hypertension in Untreated and Treated Patients With Diabetes Mellitus: Attractive But Questionable Interpretations and Response to Is Masked Hypertension Related to Diabetes Mellitus?2013Ingår i: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 62, nr 4, s. E23-E25Artikel i tidskrift (Refereegranskat)
  • 122.
    Fresard, Laure
    et al.
    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
    Smail, Craig
    Stanford Univ, Biomed Informat Program, Stanford, CA 94305 USA.
    Ferraro, Nicole M.
    Stanford Univ, Biomed Informat Program, Stanford, CA 94305 USA.
    Teran, Nicole A.
    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
    Li, Xin
    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
    Smith, Kevin S.
    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Bonner, Devon
    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Kernohan, Kristin D.
    Childrens Hosp Eastern Ontario, NSO, Ottawa, ON, Canada.
    Marwaha, Shruti
    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;Stanford Univ, Stanford Cardiovasc Inst, Sch Med, Stanford, CA 94305 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Zappala, Zachary
    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
    Balliu, Brunilda
    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
    Davis, Joe R.
    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
    Liu, Boxiang
    Stanford Univ, Sch Humanities & Sci, Dept Biol, Stanford, CA 94305 USA.
    Prybol, Cameron J.
    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
    Kohler, Jennefer N.
    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Zastrow, Diane B.
    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Reuter, Chloe M.
    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Fisk, Dianna G.
    Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA.
    Grove, Megan E.
    Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA.
    Davidson, Jean M.
    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Hartley, Taila
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    Joshi, Ruchi
    Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA.
    Strober, Benjamin J.
    Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA.
    Utiramerur, Sowmithri
    Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Ingelsson, Erik
    Stanford Univ, Stanford Cardiovasc Inst, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA.
    Battle, Alexis
    Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA;Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA.
    Bejerano, Gill
    Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Biomed Data Sci, Stanford, CA 94305 USA.
    Bernstein, Jonathan A.
    Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Ashley, Euan A.
    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA;Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Boycott, Kym M.
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    Merker, Jason D.
    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA;Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Pathol & Lab Med, Chapel Hill, NC 27515 USA;Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27515 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Wheeler, Matthew T.
    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;Stanford Univ, Stanford Cardiovasc Inst, Sch Med, Stanford, CA 94305 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Montgomery, Stephen B.
    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
    Adams, David R.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Aday, Aaron
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Alejandro, Mercedes E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Allard, Patrick
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Azamian, Mahshid S.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Bacino, Carlos A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Baker, Eva
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Balasubramanyam, Ashok
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Barseghyan, Hayk
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Batzli, Gabriel F.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Beggs, Alan H.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Behnam, Babak
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Bellen, Hugo J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Berry, Gerard T.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Bican, Anna
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Bick, David P.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Birch, Camille L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Boone, Braden E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Bostwick, Bret L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Briere, Lauren C.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Brokamp, Elly
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Brown, Donna M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Brush, Matthew
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Burke, Elizabeth A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Burrage, Lindsay C.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Butte, Manish J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Chen, Shan
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Clark, Gary D.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Coakley, Terra R.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Cogan, Joy D.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Colley, Heather A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Cooper, Cynthia M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Cope, Heidi
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Craigen, William J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    D'Souza, Precilla
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Davids, Mariska
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Dayal, Jyoti G.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Dell'Angelica, Esteban C.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Dhar, Shweta U.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Dipple, Katrina M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Donnell-Fink, Laurel A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Dorrani, Naghmeh
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Dorset, Daniel C.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Douine, Emilie D.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Draper, David D.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Dries, Annika M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Duncan, Laura
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Eckstein, David J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Emrick, Lisa T.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Eng, Christine M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Enns, Gregory M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Eskin, Ascia
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Esteves, Cecilia
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Estwick, Tyra
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Fernandez, Liliana
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Ferreira, Carlos
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Fieg, Elizabeth L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Fisher, Paul G.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Fogel, Brent L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Friedman, Noah D.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Gahl, William A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Glanton, Emily
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Godfrey, Rena A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Goldman, Alica M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Goldstein, David B.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Gould, Sarah E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Gourdine, Jean-Philippe F.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Groden, Catherine A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Gropman, Andrea L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Haendel, Melissa
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Hamid, Rizwan
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Hanchard, Neil A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    High, Frances
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Holm, Ingrid A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Hom, Jason
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Howerton, Ellen M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Huang, Yong
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Jamal, Fariha
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Jiang, Yong-hui
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Johnston, Jean M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Jones, Angela L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Karaviti, Lefkothea
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Koeller, David M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Kohane, Isaac S.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Krasnewich, Donna M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Korrick, Susan
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Koziura, Mary
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Krier, Joel B.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Kyle, Jennifer E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Lalani, Seema R.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Lau, C. Christopher
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Lazar, Jozef
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    LeBlanc, Kimberly
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Lee, Brendan H.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Lee, Hane
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Levy, Shawn E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Lewis, Richard A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Lincoln, Sharyn A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Loo, Sandra K.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Loscalzo, Joseph
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Maas, Richard L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Macnamara, Ellen F.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    MacRae, Calum A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Maduro, Valerie V.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Majcherska, Marta M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Malicdan, May Christine V.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Mamounas, Laura A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Manolio, Teri A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Markello, Thomas C.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Marom, Ronit
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Martin, G. Martin
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Martinez-Agosto, Julian A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    May, Thomas
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    McConkie-Rosell, Allyn
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    McCormack, Colleen E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    McCray, Alexa T.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Metz, Thomas O.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Might, Matthew
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Moretti, Paolo M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Morimoto, Marie
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Mulvihill, John J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Murdock, David R.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Murphy, Jennifer L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Muzny, Donna M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Nehrebecky, Michele E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Nelson, Stan F.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Newberry, J. Scott
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Newman, John H.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Nicholas, Sarah K.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Novacic, Donna
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Orange, Jordan S.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Orengo, James P.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Pallais, J. Carl
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Palmer, Christina G. S.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Papp, Jeanette C.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Parker, Neil H.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Pena, Loren D. M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Phillips, John A., III
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Posey, Jennifer E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Postlethwait, John H.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Potocki, Lorraine
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Pusey, Barbara N.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Renteria, Genecee
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Rives, Lynette
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Robertson, Amy K.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Rodan, Lance H.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Rosenfeld, Jill A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Sampson, Jacinda B.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Samson, Susan L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Schoch, Kelly
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Scott, Daryl A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Shakachite, Lisa
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Sharma, Prashant
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Shashi, Vandana
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Signer, Rebecca
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Silverman, Edwin K.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Sinsheimer, Janet S.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Spillmann, Rebecca C.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Stoler, Joan M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Stong, Nicholas
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Sullivan, Jennifer A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Sweetser, David A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Tan, Queenie K. -G.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Tifft, Cynthia J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Toro, Camilo
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Tran, Alyssa A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Urv, Tiina K.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Vilain, Eric
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Vogel, Tiphanie P.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Waggott, Daryl M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Wahl, Colleen E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Walley, Nicole M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Walsh, Chris A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Walker, Melissa
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Wan, Jijun
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Wangler, Michael F.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Ward, Patricia A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Waters, Katrina M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Webb-Robertson, Bobbie-Jo M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Westerfield, Monte
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Wise, Anastasia L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Wolfe, Lynne A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Worthey, Elizabeth A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yamamoto, Shinya
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yang, John
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yang, Yaping
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yoon, Amanda J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yu, Guoyun
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Zhao, Chunli
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Zheng, Allison
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Boycott, Kym
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    MacKenzie, Alex
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    Majewski, Jacek
    McGill Univ, Montreal, PQ, Canada.
    Brudno, Michael
    Univ Toronto, Toronto, ON, Canada.
    Bulman, Dennis
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    Dyment, David
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts2019Ingår i: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 25, nr 6, s. 911-919Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.

  • 123.
    Fuchsberger, Christian
    et al.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.;Univ Lubeck, European Acad Bolzano Bozen EURAC, Ctr Biomed, Bolzano, Italy..
    Flannick, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA..
    Teslovich, Tanya M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Agarwala, Vineeta
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA..
    Gaulton, Kyle J.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Ma, Clement
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Fontanillas, Pierre
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Moutsianas, Loukas
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    McCarthy, Davis J.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Rivas, Manuel A.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Perry, John R. B.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England.;Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.;Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Sim, Xueling
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Blackwell, Thomas W.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Robertson, Neil R.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Rayner, N. William
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Cingolani, Pablo
    McGill Univ, Sch Comp Sci, Montreal, PQ, Canada.;McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada..
    Locke, Adam E.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Tajes, Juan Fernandez
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Highland, Heather M.
    Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Human Genet Ctr, Houston, TX 77030 USA..
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Chines, Peter S.
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Lindgren, Cecilia M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Hartl, Christopher
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Chen, Han
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Huyghe, Jeroen R.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    van de Bunt, Martijn
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Pearson, Richard D.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Kumar, Ashish
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Basel, Swiss Trop & Publ Hlth Inst, Chron Dis Epidemiol, Basel, Switzerland..
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.;Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.;Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Gamazon, Eric R.
    Univ Chicago, Dept Med, Med Genet Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Lee, Jaehoon
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Chen, Yuhui
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Below, Jennifer E.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Chen, Peng
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Huang, Jinyan
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Go, Min Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Stitzel, Michael L.
    Jackson Lab Genom Med, Farmington, CT USA..
    Pasko, Dorota
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Parker, Stephen C. J.
    Univ Michigan, Dept Computat Med, Ann Arbor, MI USA.;Univ Michigan, Dept Bioinformat & Human Genet, Ann Arbor, MI USA..
    Varga, Tibor V.
    Lund Univ, Genet & Mol Epidemiol Unit, Lund Univ Diabet Ctr, Dept Clin Sci, Malmo, Sweden..
    Green, Todd
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Beer, Nicola L.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Day-Williams, Aaron G.
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Ferreira, Teresa
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Fingerlin, Tasha
    Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA..
    Horikoshi, Momoko
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Hu, Cheng
    Shanghai Jiao Tong Univ, Peoples Hosp 6, Shanghai Diabet Inst, Dept Endocrinol & Metab, Shanghai, Peoples R China..
    Huh, Iksoo
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Ikram, Mohammad Kamran
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Kim, Bong-Jo
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Kim, Yongkang
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Kim, Young Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Kwon, Min-Seok
    Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Lee, Juyoung
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Lee, Selyeong
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Lin, Keng-Han
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Maxwell, Taylor J.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Nagai, Yoshihiko
    McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada..
    Wang, Xu
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Welch, Ryan P.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Yoon, Joon
    Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Zhang, Weihua
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Barzilai, Nir
    Albert Einstein Coll Med, Dept Med, New York, NY USA.;Albert Einstein Coll Med, Dept Genet, New York, NY USA..
    Voight, Benjamin F.
    Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA..
    Han, Bok-Ghee
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Jenkinson, Christopher P.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.;South Texas Vet Hlth Care Syst, Res, San Antonio, TX USA..
    Kuulasmaa, Teemu
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland..
    Kuusisto, Johanna
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Manning, Alisa
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 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..
    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, Dept Biochem, Winston Salem, NC USA..
    Balkau, Beverley
    INSERM, Ctr Res Epidemiol & Populat Hlth, U1018, Villejuif, France..
    Stancakova, Alena
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland..
    Abboud, Hanna E.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany..
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Prabhakaran, Dorairaj
    Ctr Chron Dis Control, New Delhi, India..
    Gottesman, Omri
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Scott, James
    Univ London Imperial Coll Sci Technol & Med, Cardiovasc Sci, Natl Heart & Lung Inst, Hammersmith Campus, London, England..
    Carey, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Kwan, Phoenix
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Grant, George
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Smith, Joshua D.
    Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA..
    Neale, Benjamin M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA..
    Purcell, Shaun
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 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..
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Lee, Heung Man
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Kwak, Soo-Heon
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea..
    Zhao, Wei
    Univ Penn, Dept Med, Philadelphia, PA 19104 USA..
    Danesh, John
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England..
    Lam, Vincent K. L.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Park, Kyong Soo
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea.;Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul, South Korea.;Seoul Natl Univ, Coll Med, Seoul, South Korea..
    Saleheen, Danish
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.;Ctr Noncommunicable Dis, Karachi, Pakistan..
    So, Wing Yee
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Tam, Claudia H. T.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Afzal, Uzma
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England..
    Aguilar, David
    Baylor Coll Med, Div Cardiovasc, Houston, TX 77030 USA..
    Arya, Rector
    Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA..
    Aung, Tin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Chan, Edmund
    Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore..
    Navarro, Carmen
    IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain.;Univ Murcia, CIBERESP, Murcia, Spain.;Univ Murcia, Sch Med, Unit Prevent Med & Publ Hlth, E-30001 Murcia, Spain..
    Cheng, Ching-Yu
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Palli, Domenico
    Canc Res & Prevent Inst ISPO, Florence, Italy..
    Correa, Adolfo
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Curran, Joanne E.
    Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Rybin, Denis
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Farook, Vidya S.
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Fowler, Sharon P.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Freedman, Barry I.
    Wake Forest Sch Med, Nephrol Sect, Dept Internal Med, Winston Salem, NC USA..
    Griswold, Michael
    Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA..
    Hale, Daniel Esten
    Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA..
    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, Dept Biochem, Winston Salem, NC USA..
    Khor, Chiea-Chuen
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Paediat, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore..
    Kumar, Satish
    Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Lehne, Benjamin
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England..
    Thuillier, Dorothee
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France..
    Lim, Wei Yen
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Liu, Jianjun
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Loh, Marie
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Univ Oulu, Inst Hlth Sci, Oulu, Finland.;ASTAR, TLGM, Singapore, Singapore..
    Musani, Solomon K.
    Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39216 USA..
    Puppala, Sobha
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Scott, William R.
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England..
    Yengo, Loic
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France..
    Tan, Sian-Tsung
    Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Univ London Imperial Coll Sci Technol & Med, Cardiovasc Sci, Natl Heart & Lung Inst, Hammersmith Campus, London, England..
    Taylor, Herman A., Jr.
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Thameem, Farook
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Wilson, Gregory, Sr.
    Jackson State Univ, Coll Publ Serv, Jackson, MS USA..
    Wong, Tien Yin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Njolstad, Pal Rasmus
    Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway.;Haukeland Hosp, Dept Pediat, Bergen, Norway..
    Levy, Jonathan C.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Bonnycastle, Lori L.
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Schwarzmayr, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany..
    Fadista, Joao
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Surdulescu, Gabriela L.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Herder, Christian
    Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany..
    Groves, Christopher J.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Wieland, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany..
    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..
    Christensen, Cramer
    Vejle Hosp, Dept Internal Med & Endocrinol, Vejle, Denmark..
    Koistinen, Heikki A.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Minerva Fdn, Helsinki, Finland.;Univ Helsinki, Dept Med, Helsinki, Finland..
    Doney, Alex S. F.
    Ninewells Hosp & Med Sch, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee, Scotland..
    Kinnunen, Leena
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Esko, Tonu
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA USA..
    Farmer, Andrew J.
    Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England..
    Hakaste, Liisa
    Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland..
    Hodgkiss, Dylan
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Kravic, Jasmina
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Lyssenko, Valeriya
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Hollensted, Mette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Jorgensen, Marit E.
    Steno Diabet Ctr, Gentofte, Denmark..
    Jorgensen, Torben
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Univ Copenhagen, Inst Hlth Sci, Dept Publ Hlth, Copenhagen, Denmark.;Aalborg Univ, Med, Aalborg, Denmark..
    Ladenvall, Claes
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Justesen, Johanne Marie
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Karajamaki, Annemari
    Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland.;Vaasa Hlth Care Ctr, Ctr Diabet, Vaasa, Finland..
    Kriebel, Jennifer
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Rathmann, Wolfgang
    Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany..
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lauritzen, Torsten
    Aarhus Univ, Sect Gen Practice, Dept Publ Hlth, Aarhus, Denmark..
    Narisu, Narisu
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Linneberg, Allan
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Rigshosp, Dept Clin Expt Res, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Melander, Olle
    Lund Univ, Dept Clin Sci Hypertens & Cardiovasc, Malmo, Sweden..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    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..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci Diabet & Cardiovasc Dis, Genet Epidemiol, Malmo, Sweden..
    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..
    Qi, Qibin
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA..
    Roden, Michael
    Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Univ Dusseldorf, Fac Med, Dept Endocrinol & Diabetol, Dusseldorf, Germany..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Swift, Amy
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Rosengren, Anders H.
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Stirrups, Kathleen
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Wood, Andrew R.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Blancher, Christine
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England..
    Carneiro, Mauricio O.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Maguire, Jared
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Poplin, Ryan
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Shakir, Khalid
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Fennell, Timothy
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    DePristo, Mark
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    de Angelis, Martin Hrabe
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Expt Genet, Neuherberg, Germany.;Tech Univ Munich, Ctr Life & Food Sci Weihenstephan, Freising Weihenstephan, Germany..
    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..
    Gjesing, Anette P.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Jun, Goo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Nilsson, Peter
    Lund Univ, Dept Clin Sci, Med, Malmo, Sweden..
    Murphy, Jacquelyn
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Onofrio, Robert
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Thorand, Barbara
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    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..
    Meisinger, Christa
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Hu, Frank B.
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA..
    Isomaa, Bo
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Social Serv & Hlth Care, Pietarsaari, Finland..
    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..
    Liang, Liming
    Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Peters, Annette
    Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Huth, Cornelia
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    O'Rahilly, Stephen P.
    Univ Cambridge, Inst Metab Sci, Metab Res Labs, Cambridge, England..
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Dundee, Scotland..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.;Autonomous Univ Madrid, Univ Hosp LaPaz, Inst Invest Sanitaria Hosp Univ LaPaz IdiPAZ, Madrid, Spain.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland..
    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, Dabet & Obes Res Inst, Los Angeles, CA USA..
    Syvanen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bergman, Richard N.
    Cedars Sinai Diabet & Obes Res Inst, Los Angeles, CA USA..
    Bharadwaj, Dwaipayan
    CSIR IGIB, Funct Genom Unit, New Delhi, India..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Cho, Yoon Shin
    Hallym Univ, Dept Biomed Sci, Chunchon, South Korea..
    Chandak, Giriraj R.
    CSIR Ctr Cellular & Mol Biol, Hyderabad, Telangana, India..
    Chan, Juliana C. N.
    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..
    Chia, Kee Seng
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Daly, Mark J.
    Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA..
    Ebrahim, Shah B.
    Ctr Chron Dis Control, New Delhi, India..
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Elliott, Paul
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Jablonski, Kathleen A.
    George Washington Univ, Biostat Ctr, Rockville, MD USA..
    Lehman, Donna M.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Jia, Weiping
    Shanghai Jiao Tong Univ, 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..
    Pollin, Toni I.
    Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.;Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA..
    Sandhu, Manjinder
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Tandon, Nikhil
    All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi, India..
    Froguel, Philippe
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France.;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England.;Univ Cambridge, Inst Metab Sci, Metab Res Labs, Cambridge, England..
    Teo, Yik Ying
    Natl Univ Hlth Syst, 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, Cambs, England..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Ried, Janina S.
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany..
    DeFronzo, Ralph A.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Grallert, Harald
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Glaser, Benjamin
    Hadassah Hebrew Univ Med Ctr, Endocrinol & Metab Serv, Jerusalem, Israel..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Walker, Mark
    Newcastle Univ, Inst Cellular Med, Sch Med, Newcastle Upon Tyne, Tyne & Wear, England..
    Banks, Eric
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Gieger, Christian
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Im, Hae Kyung
    Univ Chicago, Dept Med, Med Genet Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Illig, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Hannover, NH, Germany.;Hannover Med Sch, Inst Human Genet, Hannover, NH, Germany..
    Franks, Paul W.
    Lund Univ, Genet & Mol Epidemiol Unit, Lund Univ Diabet Ctr, Dept Clin Sci, Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Buck, Gemma
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England..
    Trakalo, Joseph
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England..
    Buck, David
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England..
    Prokopenko, Inga
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, 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..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Farjoun, Yossi
    Broad Inst, Data Sci & Data Engn, Cambridge, MA USA..
    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..
    Gloyn, Anna L.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, 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..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany..
    Tuomi, Tiinamaija
    Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland.;Univ Helsinki, FIMM, Helsinki, Finland..
    Kooner, Jaspal Singh
    Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Univ London Imperial Coll Sci Technol & Med, Cardiovasc Sci, Natl Heart & Lung Inst, Hammersmith Campus, London, England.;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England..
    Lee, Jong-Young
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Park, Taesung
    Seoul Natl Univ, Dept Stat, Seoul, South Korea.;Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Donnelly, Peter
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Morris, Andrew D.
    Ninewells Hosp & Med Sch, Ctr Mol Med, Clin Res Ctr, Dundee, Scotland.;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Hattersley, Andrew T.
    Univ Exeter, Sch Med, Exeter, Devon, England..
    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, Dept Biochem, Winston Salem, NC USA..
    Collins, Francis S.
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 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, Dept Nat Sci, Haifa, Israel..
    Chambers, John C.
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Laakso, Markku
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Strom, Tim M.
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Bell, Graeme I.
    Univ Chicago, Dept Med Genet, Chicago, IL 60637 USA.;Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA..
    Blangero, John
    Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Duggirala, Ravindranath
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Tai, E. Shyong
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore.;Duke NUS Med Sch Singapore, Cardiovasc & Metab Disorders Program, Singapore, Singapore..
    McVean, Gilean
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England..
    Hanis, Craig L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Seielstad, Mark
    Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.;Blood Syst Res Inst, San Francisco, CA USA..
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Meigs, James B.
    Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA..
    Cox, Nancy J.
    Univ Chicago, Dept Med, Med Genet Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    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..
    Lander, Eric S.
    Broad Inst MIT & Harvard, Cambridge, MA USA..
    Gabriel, Stacey
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Burtt, Noel P.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Meitinger, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Groop, Leif
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.;Univ Helsinki, FIMM, Helsinki, Finland..
    Abecasis, Goncalo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Florez, Jose C.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 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 Unit, Diabet Res Ctr, Boston, MA 02114 USA..
    Scott, Laura J.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Kang, Hyun Min
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Altshuler, David
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.;MIT, Dept Biol, Cambridge, MA USA..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, 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..
    The genetic architecture of type 2 diabetes2016Ingår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 536, nr 7614, s. 41-47Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.

  • 124.
    Fugmann, Andreas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Millgård, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sarabi, Mahziar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Central and peripheral haemodynamic effects of hyperglycaemia, hyperinsulinaemia, hyperlipidaemia or a mixed meal2003Ingår i: Clinical Science, ISSN 0143-5221, E-ISSN 1470-8736, Vol. 105, nr 6, s. 715-721Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of the present study was to evaluate the haemodynamic changes during hyperinsulinaemia, hyperglycaemia or hypertriglyceridaemia in relation to those following a mixed meal. Ten subjects were subjected to hypertriglyceridaemia (3.9 mmol/l) for 2 h by an infusion of Intralipid and heparin. Nine subjects received a hyperglycaemic clamp (12.5 mmol/l) with octreotide and low-dose insulin infusion to maintain normoinsulinaemia (10 m-units/l). Ten subjects received saline for 2 h as a control and, thereafter, 2 h of normoglycaemic hyperinsulinaemic clamp (80 m-units/l). Finally, ten subjects were evaluated for 2 h following an ordinary mixed meal. Calf blood flow was measured by venous occlusion plethysmography and cardiac index by thoracic bioimpedance. Both the mixed meal and normoglycaemic hyperinsulinaemia lowered total peripheral resistance, and increased calf blood flow and cardiac index, whereas blood pressure decreased (P <0.05-0.001). Both hyperglycaemia and hypertriglyceridaemia increased calf blood flow, but blood pressure was unchanged. Total peripheral resistance was unchanged in hypertriglyceridaemia, whereas hyperglycaemia induced a significant increase. Normoglycaemic hyperinsulinaemia induced a haemodynamic pattern similar, but to a lesser extent, to the pattern seen following a mixed meal. Hyperinsulinaemia seems to be a major mediator of the haemodynamic response, but other factors are obviously also of great importance. Hypertriglyceridaemia and hyperglycaemia induced haemodynamic responses that are not similar to those seen following a mixed meal.

  • 125.
    Fugmann, Andreas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sarabi, Mahziar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlström, Brita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lithell, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Blood flow is an important determinant of forearm glucose uptake following a mixed meal2003Ingår i: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 40, nr 3, s. 113-117Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Insulin-mediated vasodilation has been suggested to be of importance for glucose uptake during normoglycemic hyperinsulinemia. If this also is valid after an ordinary mixed meal remains to be evaluated. Forearm blood flow (FBF) and forearm glucose uptake change (evaluated by venous occlusion plethysmography) and glucose arteriovenous differences were evaluated over 120 minutes in 10 healthy volunteers following an ordinary mixed meal (700-900 kcal, 34% of energy from fat). Fasting arterial glucose level was 4.9+/-0.9 mmol/l, and the maximum glucose level was reached 30 minutes after the start of ingestion (6.6+/-0.8 mmol/l, p<0.0001). Plasma insulin levels were increased four-fold. FBF increased rapidly within 20 minutes after the start of ingestion and reached its maximum after 50 minutes (94% higher than baseline level, p<0.01). After 2 hours FBF was still substantially elevated (75% above baseline level, p<0.01). Forearm glucose uptake increased fivefold already after 20 minutes ( p<0.01). During the 2 hours, the increase in FBF contributed to 41% of the forearm glucose uptake ( p<0.05). The present study showed that the increase in FBF seen after an ordinary mixed meal is important for the change in forearm glucose uptake. These results support the view that modulation of limb blood flow is a determinant of glucose uptake.

  • 126. Ganna, Andrea
    et al.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    1-acyl-sn-glycero-3-phosphocholine Levels are Related to Obesity and Several Markers of Subclinical CV Disease and its Biosynthesis is Associated With Genetic Variants in the 9p21 Region2013Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, nr 22Artikel i tidskrift (Övrigt vetenskapligt)
  • 127.
    Ganna, Andrea
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lee, Woojoo
    Broeckling, Corey D.
    Kumar, Jitender
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Hägg, Sara
    Stenemo, Markus
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Magnusson, Patrik K.E.
    Prenni, Jessica E.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Pawitan, Yudi
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Large-scale non-targeted metabolomic profiling in three human population-based studies2016Ingår i: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 12, artikel-id 4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Non-targeted metabolomic profiling is used to simultaneously assess a large part of the metabolome in a biological sample. Here, we describe both the analytical and computational methods used to analyze a large UPLC–Q-TOF MS-based metabolomic profiling effort using plasma and serum samples from participants in three Swedish population-based studies of middle-aged and older human subjects: TwinGene, ULSAM and PIVUS. At present, more than 200 metabolites have been manually annotated in more than 3600 participants using an in-house library of standards and publically available spectral databases. Data available at the metabolights repository include individual raw unprocessed data, processed data, basic demographic variables and spectra of annotated metabolites. Additional phenotypical and genetic data is available upon request to cohort steering committees. These studies represent a unique resource to explore and evaluate how metabolic variability across individuals affects human diseases.

  • 128.
    Ganna, Andrea
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Broeckling, Corey D
    Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, Colorado, United States of America.
    Hedman, Åsa K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Magnusson, Patrik K E
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Pedersen, Nancy L
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Zilmer, Mihkel
    Department of Biochemistry, Centre of Excellence for Translational Medicine, University of Tartu, Tartu, Estonia.
    Prenni, Jessica
    Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, Colorado, United States of America.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart Disease2014Ingår i: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, nr 12, s. e1004801-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18∶1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001), lysophosphatidylcholine 18∶2 (HR = 0.81, P-value<0.001), monoglyceride 18∶2 (MG 18∶2; HR = 1.18, P-value = 0.011) and sphingomyelin 28∶1 (HR = 0.85, P-value = 0.015)]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18∶2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18∶2. MG 18∶2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10-7 for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18∶2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development.

  • 129.
    Gaulton, Kyle J.
    et al.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Stanford Univ, Dept Genet, Stanford, CA 94305 USA..
    Ferreira, Teresa
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Lee, Yeji
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Raimondo, Anne
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Maegi, Reedik
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    Reschen, Michael E.
    Univ Oxford, Nuffield Dept Med, Ctr Cellular & Mol Physiol, Oxford, England..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Locke, Adam
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Rayner, N. William
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Wellcome Trust Sanger Inst, Hinxton, England..
    Robertson, Neil
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Scott, Robert A.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, Med Res Council MRC Epidemiol Unit, Cambridge, England..
    Prokopenko, Inga
    Univ London Imperial Coll Sci Technol & Med, Genom Common Dis, London, England..
    Scott, Laura J.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Green, Todd
    Broad Inst Harvard & MIT, Cambridge, MA USA..
    Sparso, Thomas
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Thuillier, Dorothee
    European Genom Inst Diabet, Lille Inst Biol, Lille, France..
    Yengo, Loic
    European Genom Inst Diabet, Lille Inst Biol, Lille, France..
    Grallert, Harald
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Wahl, Simone
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Franberg, Mattias
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden.;Sci Life Lab, Stockholm, Sweden.;Stockholm Univ, Dept Numer Anal & Comp Sci, S-10691 Stockholm, Sweden..
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden..
    Kestler, Hans
    Fritz Lipmann Inst, Leibniz Inst Age Res, Jena, Germany.;Univ Ulm, Med Syst Biol, D-89069 Ulm, Germany..
    Chheda, Himanshu
    Finnish Inst Mol Med, Helsinki, Finland..
    Eisele, Lewin
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany..
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Steinthorsdottir, Valgerdur
    deCODE Genet Amgen Inc, Reykjavik, Iceland..
    Thorleifsson, Gudmar
    deCODE Genet Amgen Inc, Reykjavik, Iceland..
    Qi, Lu
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.;Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA..
    Karssen, Lennart C.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    van Leeuwen, Elisabeth M.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Willems, Sara M.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, Med Res Council MRC Epidemiol Unit, Cambridge, England.;Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Li, Man
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA..
    Chen, Han
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA..
    Fuchsberger, Christian
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Kwan, Phoenix
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Ma, Clement
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Linderman, Michael
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Thomsen, Soren K.
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Rundle, Jana K.
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Beer, Nicola L.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    van de Bunt, Martijn
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Chalisey, Anil
    Univ Oxford, Nuffield Dept Med, Ctr Cellular & Mol Physiol, Oxford, England..
    Kang, Hyun Min
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Voight, Benjamin F.
    Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA..
    Abecasis, Goncalo R.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Almgren, Peter
    Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden..
    Baldassarre, Damiano
    IRCCS, Ctr Cardiol Monzino, Milan, Italy.;Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy..
    Balkau, Beverley
    Ctr Rech Epidemiol & Sante Populat CESP, INSERM, U1018, Villejuif, France.;Univ Paris 11, UMRS 1018, Villejuif, France..
    Benediktsson, Rafn
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Landspitali Univ Hosp, Reykjavik, Iceland..
    Blueher, Matthias
    Univ Leipzig, Integrated Treatment & Res IFB Ctr Adipos Dis, D-04109 Leipzig, Germany.;Univ Leipzig, Dept Med, D-04109 Leipzig, Germany..
    Boeing, Heiner
    German Inst Human Nutr, Potsdam, Germany..
    Bonnycastle, Lori L.
    NHGRI, US NIH, Bethesda, MD 20892 USA..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Burtt, Noel P.
    Broad Inst Harvard & MIT, Cambridge, MA USA..
    Carey, Jason
    Broad Inst Harvard & MIT, Cambridge, MA USA..
    Charpentier, Guillaume
    Corbeil Essonnes Hosp, Endocrinol Diabetol Unit, Corbeil Essonnes, France..
    Chines, Peter S.
    NHGRI, US NIH, Bethesda, MD 20892 USA..
    Cornelis, Marilyn C.
    Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA..
    Couper, David J.
    Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA..
    Crenshaw, Andrew T.
    Broad Inst Harvard & MIT, Cambridge, MA USA..
    van Dam, Rob M.
    Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore..
    Doney, Alex S. F.
    Univ Dundee, Ninewells Hosp, Biomed Res Inst, Ctr Diabet Res, Dundee, Scotland.;Univ Dundee, Ninewells Hosp, Biomed Res Inst, Pharmacogen Ctr, Dundee, Scotland..
    Dorkhan, Mozhgan
    Lund Univ, Ctr Diabet, Dept Clin Sci Malmo, Novo Nordisk Scandinavia, Malmo, Sweden..
    Edkins, Sarah
    Wellcome Trust Sanger Inst, Hinxton, England..
    Eriksson, Johan G.
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.;Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Esko, Tonu
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA..
    Eury, Elodie
    CNRS, UMR 8199, Inst Biol, Lille, France.;Univ Lille 2, Inst Pasteur, Lille, France..
    Fadista, Joao
    Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden..
    Flannick, Jason
    Broad Inst Harvard & MIT, Cambridge, MA USA..
    Fontanillas, Pierre
    Broad Inst Harvard & MIT, Cambridge, MA USA..
    Fox, Caroline
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA USA..
    Franks, Paul W.
    Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden.;Lund Univ, Dept Clin Sci, Malmo, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Gertow, Karl
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden..
    Gieger, Christian
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Gigante, Bruna
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden..
    Gottesman, Omri
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Grant, George B.
    Broad Inst Harvard & MIT, Cambridge, MA USA..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Groves, Christopher J.
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Hassinen, Maija
    Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Have, Christian T.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Herder, Christian
    Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;Partner Site Dusseldorf, German Ctr Diabet Res, Dusseldorf, Germany..
    Holmen, Oddgeir L.
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Nord Trondelag Hlth Study HUNT Res Ctr, Levanger, Norway..
    Hreidarsson, Astradur B.
    Landspitali Univ Hosp, Reykjavik, Iceland..
    Humphries, Steve E.
    UCL, Inst Cardiovasc Sci, British Heart Fdn BHF Labs, Cardiovasc Genet, London, England..
    Hunter, David J.
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Jonsson, Anna
    Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden..
    Jorgensen, Marit E.
    Steno Diabet Ctr, DK-2820 Gentofte, Denmark..
    Jorgensen, Torben
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.;Aalborg Univ, Fac Med, Aalborg, Denmark..
    Kao, Wen-Hong L.
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA..
    Kerrison, Nicola D.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, Med Res Council MRC Epidemiol Unit, Cambridge, England..
    Kinnunen, Leena
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland..
    Klopp, Norman
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany..
    Kong, Augustine
    deCODE Genet Amgen Inc, Reykjavik, Iceland..
    Kovacs, Peter
    Univ Leipzig, Integrated Treatment & Res IFB Ctr Adipos Dis, D-04109 Leipzig, Germany.;Univ Leipzig, Dept Med, D-04109 Leipzig, Germany..
    Kraft, Peter
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA..
    Kravic, Jasmina
    Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden..
    Langford, Cordelia
    Wellcome Trust Sanger Inst, Hinxton, England..
    Leander, Karin
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden..
    Liang, Liming
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA..
    Lichtner, Peter
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Broad Inst Harvard & MIT, Cambridge, MA USA..
    Lindholm, Eero
    Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden..
    Linneberg, Allan
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark.;Rigshosp, Copenhagen Univ Hosp, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Lobbens, Stephane
    CNRS, UMR 8199, Inst Biol, Lille, France.;Univ Lille 2, Inst Pasteur, Lille, France..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, Med Res Council MRC Epidemiol Unit, Cambridge, England..
    Lyssenko, Valeriya
    Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden.;Steno Diabet Ctr, DK-2820 Gentofte, Denmark..
    Mannisto, Satu
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland..
    McLeod, Olga
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden..
    Meyer, Julia
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    Mirza, Ghazala
    Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Guys & St Thomas Hosp, Genom Core Facil, Biomed Res Ctr, London, England..
    Muehleisen, Thomas W.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany.;Res Ctr Julich, Inst Neurosci & Med INM 1, Julich, Germany..
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.;Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Neuherberg, Germany.;Partner Site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Navarro, Carmen
    Inst Murciano Invest Biosanitaria Virgen de la Ar, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain.;CIBERESP, Madrid, Spain.;Univ Murcia, Dept Hlth & Social Sci, Murcia, Spain..
    Noethen, Markus M.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany..
    Oskolkov, Nikolay N.
    Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden..
    Owen, Katharine R.
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Churchill Hosp, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford OX3 7LJ, England..
    Palli, Domenico
    Canc Res & Prevent Inst ISPO, Florence, Italy..
    Pechlivanis, Sonali
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany..
    Peltonen, Leena
    Wellcome Trust Sanger Inst, Hinxton, England.;Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland..
    Perry, John R. B.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, Med Res Council MRC Epidemiol Unit, Cambridge, England..
    Platou, Carl G. P.
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Nord Trondelag Hlth Study HUNT Res Ctr, Levanger, Norway.;Nord Trondelag Hlth Trust, Levanger Hosp, Dept Internal Med, Levanger, Norway..
    Roden, Michael
    Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;Partner Site Dusseldorf, German Ctr Diabet Res, Dusseldorf, Germany.;Univ Hosp Dusseldorf, Dept Endocrinol & Diabetol, Dusseldorf, Germany..
    Ruderfer, Douglas
    Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY 10029 USA..
    Rybin, Denis
    Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Utrecht, Netherlands..
    Sennblad, Bengt
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden.;Sci Life Lab, Stockholm, Sweden..
    Sigurdsson, Gunnar
    Landspitali Univ Hosp, Reykjavik, Iceland.;Iceland Heart Assoc, Kopavogur, Iceland..
    Stancakova, Alena
    Univ Eastern Finland, Dept Med, Kuopio, Finland.;Kuopio Univ Hosp, SF-70210 Kuopio, Finland..
    Steinbach, Gerald
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Ulm, Dept Clin Chem & Cent Lab, D-89069 Ulm, Germany..
    Storm, Petter
    Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Neuherberg, Germany..
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Sun, Qi
    Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA..
    Thorand, Barbara
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Tikkanen, Emmi
    Stanford Univ, Dept Genet, Stanford, CA 94305 USA.;Finnish Inst Mol Med, Helsinki, Finland.;Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland..
    Tonjes, Anke
    Univ Leipzig, Integrated Treatment & Res IFB Ctr Adipos Dis, D-04109 Leipzig, Germany.;Univ Leipzig, Dept Med, D-04109 Leipzig, Germany..
    Trakalo, Joseph
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Tremoli, Elena
    IRCCS, Ctr Cardiol Monzino, Milan, Italy.;Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy..
    Tuomi, Tiinamaija
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Finnish Inst Mol Med, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Helsinki Univ Hosp, Abdominal Ctr, Dept Endocrinol, Helsinki, Finland.;Univ Helsinki, Res Program Diabet & Obes, Helsinki, Finland..
    Wennauer, Roman
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands..
    Wiltshire, Steven
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Wood, Andrew R.
    Univ Oxford, Nuffield Dept Med, Ctr Cellular & Mol Physiol, Oxford, England.;Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Hinxton, England..
    Dunham, Ian
    Wellcome Trust Sanger Inst, Hinxton, England.;European Mol Biol Lab, EBI, Hinxton, England..
    Birney, Ewan
    Wellcome Trust Sanger Inst, Hinxton, England.;European Mol Biol Lab, EBI, Hinxton, England..
    Pasquali, Lorenzo
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, Med Res Council MRC Epidemiol Unit, Cambridge, England.;Univ London Imperial Coll Sci Technol & Med, Genom Common Dis, London, England.;Germans Trias & Pujol Univ Hosp & Res Inst, Div Endocrinol, Badalona, Spain.;Josep Carreras Leukaemia Res Inst, Badalona, Spain.;CIBERDEM, Barcelona, Spain..
    Ferrer, Jorge
    Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England.;Inst Invest Biomed August Pi & Sunyer, Ctr Esther Koplowitz, Barcelona, Spain..
    Loos, Ruth J. F.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, Med Res Council MRC Epidemiol Unit, Cambridge, England.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;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. Harvard Univ, Sch Med, Dept Med, Boston, MA USA..
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Florez, Jose C.
    Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Pankow, James S.
    Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    van Duijn, Cornelia
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.;Netherlands Consortium Hlth Ageing, Netherlands Genom Initiat, Rotterdam, Netherlands.;Ctr Med Syst Biol, Rotterdam, Netherlands..
    Sijbrands, Eric
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands..
    Meigs, James B.
    Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA..
    Hu, Frank B.
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA..
    Thorsteinsdottir, Unnur
    deCODE Genet Amgen Inc, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Stefansson, Kari
    deCODE Genet Amgen Inc, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Lakka, Timo A.
    Kuopio Res Inst Exercise Med, Kuopio, Finland.;Univ Eastern Finland, Inst Biomed Physiol, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland..
    Stumvoll, Michael
    Univ Leipzig, Integrated Treatment & Res IFB Ctr Adipos Dis, D-04109 Leipzig, Germany.;Univ Leipzig, Dept Med, D-04109 Leipzig, Germany..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Keinanen-Kiukaanniemi, Sirkka M.
    Univ Oulu, Inst Hlth Sci, Fac Med, Oulu, Finland.;Oulu Univ Hosp, Unit Gen Practice, Oulu, Finland..
    Korpi-Hyovalti, Eeva
    South Ostrobothnia Cent Hosp, Seinajoki, Finland..
    Saaristo, Timo E.
    Finnish Diabet Assoc, Tampere, Finland.;Pirkanmaa Dist Hosp, Tampere, Finland..
    Saltevo, Juha
    Cent Finland Cent Hosp, Dept Med, Jyvasklya, Finland..
    Kuusisto, Johanna
    Univ Eastern Finland, Dept Med, Kuopio, Finland.;Kuopio Univ Hosp, SF-70210 Kuopio, Finland..
    Laakso, Markku
    Univ Eastern Finland, Dept Med, Kuopio, Finland.;Kuopio Univ Hosp, SF-70210 Kuopio, Finland..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia..
    Erbel, Raimund
    Univ Duisdurg Essen, Univ Hosp Essen, West German Heart Ctr, Clin Cardiol, Essen, Germany..
    Joecke, Karl-Heinz
    Univ Eastern Finland, Inst Biomed Physiol, Kuopio, Finland..
    Moebus, Susanne
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany..
    Ripatti, Samuli
    Stanford Univ, Dept Genet, Stanford, CA 94305 USA.;Wellcome Trust Sanger Inst, Hinxton, England.;Finnish Inst Mol Med, Helsinki, Finland.;Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland.;Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Boehm, Bernhard O.
    Univ Med Ctr Ulm, Dept Internal Med, Div Endocrinol & Diabet, Ulm, Germany.;Univ London Imperial Coll Sci Technol & Med, Lee Kong Chian Sch Med, London SW7 2AZ, England.;Nanyang Technol Univ, Singapore 639798, Singapore..
    Bergman, Richard N.
    Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA..
    Collins, Francis S.
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;NHGRI, US NIH, Bethesda, MD 20892 USA..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Koistinen, Heikki
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Dept Med, Div Endocrinol, Helsinki, Finland.;Minerva Fdn, Helsinki, Finland..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.;Hosp Univ La Paz, Inst Invest Sanitaria, Madrid, Spain.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;King Abdulaziz Univ, Diabet Res Grp, Jeddah 21413, Saudi Arabia..
    Hveem, Kristian
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Nord Trondelag Hlth Study HUNT Res Ctr, Levanger, Norway..
    Njolstad, Inger
    Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway..
    Deloukas, Panagiotis
    Wellcome Trust Sanger Inst, Hinxton, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Donnelly, Peter J.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Dept Stat, Oxford OX1 3TG, England..
    Frayling, Timothy M.
    Univ Oxford, Nuffield Dept Med, Ctr Cellular & Mol Physiol, Oxford, England.;Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Hattersley, Andrew T.
    Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter, Devon, England..
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden..
    Illig, Thomas
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany..
    Peters, Annette
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;German Ctr Diabet Res, Neuherberg, Germany.;Partner Site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Cauchi, Stephane
    European Genom Inst Diabet, Lille Inst Biol, Lille, France..
    Sladek, Rob
    Ctr Hosp Univ Montreal, Ctr Rech, Montreal Diabet Res Ctr, Montreal, PQ, Canada.;McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada..
    Froguel, Philippe
    Univ London Imperial Coll Sci Technol & Med, Genom Common Dis, London, England.;CNRS, UMR 8199, Inst Biol, Lille, France.;Univ Lille 2, Inst Pasteur, Lille, France..
    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..
    Morris, Andrew D.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Palmer, Collin N. A.
    Univ Dundee, Ninewells Hosp, Biomed Res Inst, Ctr Diabet Res, Dundee, Scotland.;Univ Dundee, Ninewells Hosp, Biomed Res Inst, Pharmacogen Ctr, Dundee, Scotland..
    Kathiresan, Sekar
    Broad Inst Harvard & MIT, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Melander, Olle
    Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden..
    Nilsson, Peter M.
    Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden..
    Groop, Leif C.
    Finnish Inst Mol Med, Helsinki, Finland.;Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Cambridge, Metab Res Labs, Wellcome Trust MRC Inst Metab Sci, Cambridge, England.;Cambridge Biomed Res Ctr, Natl Inst Hlth Res, Cambridge, England..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, Med Res Council MRC Epidemiol Unit, Cambridge, England..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, Med Res Council MRC Epidemiol Unit, Cambridge, England..
    O'Callaghan, Christopher A.
    Univ Oxford, Nuffield Dept Med, Ctr Cellular & Mol Physiol, Oxford, England..
    Gloyn, Anna L.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Churchill Hosp, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford OX3 7LJ, England..
    Altshuler, David
    Broad Inst Harvard & MIT, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA.;Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.;Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA USA. Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Teslovich, Tanya M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Churchill Hosp, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford OX3 7LJ, England..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool L69 3BX, Merseyside, England..
    Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci2015Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, nr 12, s. 1415-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.

  • 130.
    Genberg, Margareta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Andrén, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Hedenström, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Malinovschi, Andrei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Commonly used reference values underestimate oxygen uptake in healthy, 50-year-old Swedish women.2018Ingår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, nr 1, s. 25-33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cardiopulmonary exercise testing (CPET) is the gold standard among clinical exercise tests. It combines a conventional stress test with measurement of oxygen uptake (VO2 ) and CO2 production. No validated Swedish reference values exist, and reference values in women are generally understudied. Moreover, the importance of achieved respiratory exchange ratio (RER) and the significance of breathing reserve (BR) at peak exercise in healthy individuals are poorly understood. We compared VO2 at maximal load (peakVO2 ) and anaerobic threshold (VO2@AT ) in healthy Swedish individuals with commonly used reference values, taking gender into account. Further, we analysed maximal workload and peakVO2 with regard to peak RER and BR. In all, 181 healthy, 50-year-old individuals (91 women) performed CPET. PeakVO2 was best predicted using Jones et al. (100·5%), while SHIP reference values underestimated peakVO2 most: 112·5%. Furthermore, underestimation of peakVO2 in women was found for all studied reference values (P<0·001) and was largest for SHIP: women had 128% of predicted peakVO2 , while men had 104%. PeakVO2 was similar in subjects with peak RER of 1-1·1 and RER > 1·1 (2 328·7 versus 2 176·7 ml min(-1) , P = 0·11). Lower BR (≤30%) related to significantly higher peakVO2 (P<0·001). In conclusion, peakVO2 was best predicted by Jones. All studied reference values underestimated oxygen uptake in women. No evidence for demanding RER > 1·1 in healthy individuals was found. A lowered BR is probably a normal response to higher workloads in healthy individuals.

  • 131. Gonzalez, Manuel
    et al.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Soderberg, Stefan
    Leptin and endothelial function in the elderly: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2013Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 228, nr 2, s. 485-490Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Leptin levels are elevated in obese humans. Several studies have shown an association between hyperleptinemia and development of atherosclerosis and cardiovascular disease (CVD), but the relationship between leptin and vascular function remains unclear. Aim: To evaluate associations between circulating plasma leptin and measures of vascular function in a large sample of elderly individuals from the community. Methods: This cross-sectional study included 1016 subjects aged 70 (50% women) from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The invasive technique forearm plethysmography with intra-arterial infusions of acetylcholine and sodium nitroprusside was used for estimation of endothelial dependent vasodilatation (EDV) and endothelial independent vasodilatation (EIDV), respectively, in resistance arteries, and the non-invasive technique ultrasound assessed flow mediated vasodilation (FMD) in conduit arteries. The aortic augmentation index (AoAI), a surrogate measure of arterial stiffness, was evaluated by pulse wave analysis. Associations of vascular function, arterial stiffness and blood pressure with leptin were explored. Results: In sex-adjusted models, high levels of leptin were inversely associated with EDV and EIDV. These associations remained after stratification for sex, traditional risk factors of CVD and insulin resistance, but were attenuated after taking a measure of obesity (body mass index) into account. In addition, leptin associated with arterial stiffness and systolic and diastolic blood pressure. Conclusion: Hyperleptinemia associated inversely with vasodilatation in resistance arteries. Furthermore, hyperleptinemia associated with arterial stiffness and hypertension. These associations were attenuated after adjusting for body mass index suggesting that leptin may be the mediator between obesity and impaired vascular function.

  • 132. Gu, Yu-Mei
    et al.
    Thijs, Lutgarde
    Li, Yan
    Asayama, Kei
    Boggia, Jose
    Hansen, Tine W.
    Liu, Yan-Ping
    Ohkubo, Takayoshi
    Bjorklund-Bodegard, Krishna
    Jeppesen, Jorgen
    Dolan, Eamon
    Torp-Pedersen, Christian
    Kuznetsova, Tatiana
    Stolarz-Skrzypek, Katarzyna
    Tikhonoff, Valerie
    Malyutina, Sofia
    Casiglia, Edoardo
    Nikitin, Yuri
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sandoya, Edgardo
    Kawecka-Jaszcz, Kalina
    Imai, Yutaka
    Mena, Luis J.
    Wang, Jiguang
    O'Brien, Eoin
    Verhamme, Peter
    Filipovsky, Jan
    Maestre, Gladys E.
    Staessen, Jan A.
    Outcome-Driven Thresholds for Ambulatory Pulse Pressure in 9938 Participants Recruited From 11 Populations2014Ingår i: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 63, nr 2, s. 229-237Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Evidence-based thresholds for risk stratification based on pulse pressure (PP) are currently unavailable. To derive outcome-driven thresholds for the 24-hour ambulatory PP, we analyzed 9938 participants randomly recruited from 11 populations (47.3% women). After age stratification (<60 versus >= 60 years) and using average risk as reference, we computed multivariable-adjusted hazard ratios (IIRs) to assess risk by tenths of the PP distribution or risk associated with stepwise increasing (+1 mm Hg) PP levels. All adjustments included mean arterial pressure. Among 6028 younger participants (68 853 person-years), the risk of cardiovascular (HR, 1.58; P=0.011) or cardiac (HR, 1.52; P=0.056) events increased only in the top PP tenth (mean, 60.6 mm Hg). Using stepwise increasing PP levels, the lower boundary of the 95% confidence interval of the successive thresholds did not cross unity. Among 3910 older participants (39 923 person-years), risk increased (P <= 0.028) in the top PP tenth (mean, 76.1 mm Hg). HRs were 1.30 and 1.62 for total and cardiovascular mortality, and 1.52, 1.69, and 1.40 for all cardiovascular, cardiac, and cerebrovascular events. The lower boundary of the 95% confidence interval of the HRs associated with stepwise increasing PP levels crossed unity at 64 mm Hg. While accounting for all covariables, the top tenth of PP contributed less than 0.3% (generalized R-2 statistic) to the overall risk among the elderly. Thus, in randomly recruited people, ambulatory PP does not add to risk stratification below age 60; in the elderly, PP is a weak risk factor with levels below 64 mm Hg probably being innocuous.

  • 133. Gustafsson, Stefan
    et al.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Soderberg, Stefan
    Zilmer, Mihkel
    Hulthe, Johannes
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Oxidative Stress and Inflammatory Markers in Relation to Circulating Levels of Adiponectin2013Ingår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, nr 7, s. 1467-1473Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Previous epidemiological studies together with animal studies have suggested an association between adiponectin and oxidative stress and inflammation, but community-based studies are lacking. Our objective was to investigate the relative importance of oxidative stress and inflammatory markers, representing different pathways in relation to adiponectin. Design and Methods: In a cross-sectional sample of 929 70-year-old individuals (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors study, relations between serum adiponectin and oxidative stress [conjugated dienes (CD), homocysteine, total antioxidant capacity, oxidized low-density lipoprotein (OxLDL), OxLDL antibodies, baseline CD of LDL, glutathione (GSH), total glutathione (TGSH), glutathione disulfide], circulation interleukins (IL-6, IL-8), other cytokines [tumor necrosis factor alpha, monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor], cell adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, P-selectin, L-selectin), and systemic inflammatory markers [C-reactive protein (CRP), leukocyte count] in separate models were investigated. Results: In age- and sex-adjusted, as well as multivariable-adjusted models, adiponectin was significantly and positively associated with GSH, log TGSH, whereas an inverse association was observed for CD and log EGF. An inverse association between adiponectin and MCP-1, log E-selectin, and log CRP was significant in age- and sex-adjusted models, but not in multivariable-adjusted models. Conclusions: Our results imply that higher levels of adiponectin are associated with a more beneficial oxidative stress profile, with higher levels of principal anti-oxidative GSH and total GSH together with lower levels of lipid peroxidation, possibly through shared pathways. Further studies are needed to investigate whether changes in the oxidative stress profile may be a mechanism linking adiponectin with type 2 diabetes and/or cardiovascular disease.

  • 134.
    Haenni, A
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Reneland, R
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Lind, L
    Institutionen för medicinska vetenskaper. Akut- och internmedicin.
    Lithell, H
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Serum aldosterone changes during hyperinsulinemia are correlated to body mass index and insulin sensitivity in patients with essential hypertension.2001Ingår i: J Hypertens, ISSN 0263-6352, Vol. 19, nr 1, s. 107-12Artikel i tidskrift (Övrigt vetenskapligt)
  • 135.
    Haenni, Arvo
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Johansson, Kristina
    Institutionen för medicinska vetenskaper.
    Lind, Lars
    Institutionen för medicinska vetenskaper.
    Lithell, Hans
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Magnesium infusion improves endothelium-dependent vasodilation in the human forearm.2002Ingår i: Am J Hypertens, ISSN 0895-7061, Vol. 15, nr 1 Pt 1, s. 10-5Artikel i tidskrift (Refereegranskat)
  • 136.
    Haenni, Arvo
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Reneland, Rikard
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Andersson, Per-Erik
    Lind, Lars
    Institutionen för medicinska vetenskaper.
    Lithell, Hans
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Skeletal muscle magnesium content is correlated with plasma glucose concentration in patients with essential hypertension treated with lisinopril or bendrofluazide.2002Ingår i: Am J Hypertens, ISSN 0895-7061, Vol. 15, nr 8, s. 735-8Artikel i tidskrift (Refereegranskat)
  • 137.
    Hagström, Emil
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ahlström, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Parathyroid hormone and calcium are independently associated with subclinical vascular disease in a community-based cohort2015Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 238, nr 2, s. 420-426Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    Diseases with abnormal levels of parathyroid hormone (PTH) and calcium, such as primary and secondary hyperparathyroidism, are associated with an increased risk of cardiovascular morbidity and mortality. However, there is paucity on the association between calcium, PTH and abnormalities in the vascular system in the general population.

    METHODS:

    In the PIVUS study (Prospective Investigation of the Vasculature in Uppsala Seniors), a community based cohort of 70-year old men and women (n = 1016), the associations between s-calcium, p-PTH and endothelial function, arterial stiffness and blood pressures were investigated, adjusting for cardiovascular risk factors and mineral metabolism.

    RESULTS:

    In multivariable linear regression models 1 SD increase in calcium was associated with 1.1 units decrease in the stroke volume/pulse pressure ratio and 0.06 decrease in common carotid artery distensibility (p < 0.001) indicative of increased arterial stiffness. Further, calcium was associated with increasing calculated central pulse pressure with 1.3 mmHg elevation per 1 SD increase in calcium (p < 0.05). 1 SD increase in PTH was associated with 1.9 and 1.0 mmHg increase in intra-arterially measured brachial artery systolic and diastolic blood pressures, respectively (p < 0.01), as well as 1.6 and 0.9 mmHg increase in calculated central systolic and diastolic blood pressures (p < 0.05). PTH was not associated with arterial stiffness, endothelial function or pulse pressure.

    CONCLUSION:

    In a large community-based sample of elderly, calcium was independently associated with increased arterial stiffness, and PTH independently to intra-arterial peripheral and calculated central blood pressures. The findings indicate a possible link between the vasculature and mineral metabolism.

  • 138.
    Hagström, Emil
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Nylander, Ruta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Arnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Plasma Parathyroid Hormone Is Associated with Vascular Dementia and Cerebral Hyperintensities in Two Community-Based Cohorts2014Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, nr 11, s. 4181-4189Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context:

    In diseases with increased PTH such as hyperparathyroidism and chronic renal failure, dementia is common. Little is known of PTH and dementia in the community.

    Objective:

    We sought to investigate relations between PTH, clinical dementia and cerebral micro-vascular disease.

    Setting and Design:

    The Uppsala Longitudinal Study Of Adult Men (ULSAM) was prospective, baseline, 1991-1995; followup, 15.8 years. The Prospective Investigation Of The Vasculature In Uppsala Seniors (PIVUS) was cross-sectional, baseline, 2001. Both settings were community based.

    Participants and Main Outcome Measure:

    In the ULSAM study of 998 men (age 71) the association between PTH and dementia was investigated. In the PIVUS study of 406 men and women (age 70) the relation between PTH and magnetic resonance imaging signs of cerebral small vascular disease was investigated.

    Results:

    During followup, 56 individuals were diagnosed with vascular, 91 with Alzheimer's, and 59 with other dementias. In Cox-regression analyses, higher PTH was associated with vascular dementia (hazard ratio per 1 SD increase of PTH, 1.41; P < .01), but not with other dementias. The top tertile of PTH accounted for 18.5% of the population-attributable risk for vascular dementia, exceeding all other risk factors. In linear regression analysis in PIVUS, PTH was associated with increasing white matter hyperintensities (WMHI), reflecting increasing burden of cerebral small vessel disease (1 SD PTH increase, 0.31 higher category of WMHI; P = .016). All models were adjusted for vascular risk factors and mineral metabolism.

    Conclusions:

    In two community-based samples, PTH predicted clinically diagnosed and neuroimaging indices of vascular dementia and cerebral small vessel disease. Our data suggest a role for PTH in the development of vascular dementia.

  • 139.
    Hagström, Emil
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Hansen, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Arnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Plasma-Parathyroid Hormone Is Associated With Subclinical and Clinical Atherosclerotic Disease in 2 Community-Based Cohorts2014Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 34, nr 7, s. 1567-73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Cardiovascular risk factors have different impact on different arterial territories. Diseases with elevated circulating parathyroid hormone (PTH) such as primary hyperparathyroidism and chronic renal failure have been shown to be associated with an increased risk of cardiovascular disease, predominantly heart or cerebrovascular diseases. However, data on the associations between circulating PTH and peripheral atherosclerosis are limited.

    APPROACH AND RESULTS: Two prospective, community-based studies were used. In 306 men and women, who were 70 years old, from the Prospective investigation of the vasculature in Uppsala seniors (PIVUS) study, cross-sectional relations between PTH and atherosclerotic burden assessed by whole-body magnetic resonance angiography were investigated. In 998 men, who were 71 years old, from the Uppsala longitudinal study of adult men (ULSAM) study, the association between PTH concentration and risk of subsequent nonfatal atherosclerotic disease (excluding coronary or cerebrovascular disease) was investigated. Adjusting for established vascular risk factors, PTH was associated with burden of atherosclerosis (increase in total atherosclerotic score per SD PTH increase: 0.04, 0.003-0.08; P=0.03) in the PIVUS study. During follow-up in the ULSAM study (median 16.7 years), 89 men were diagnosed with nonfatal atherosclerotic disease. In Cox-regression analyses adjusting for established vascular risk factors and mineral metabolism, higher PTH was associated with an increased risk of nonfatal atherosclerotic disease (hazard ratio for 1 SD increase of PTH: 1.55, 1.33-1.88; P<0.0001). Results were similar when including fatal atherosclerotic disease in the outcome.

    CONCLUSIONS: In 2 independent community-based cohorts, PTH was associated to the degree of atherosclerosis and risk of clinically overt atherosclerotic disease, respectively. Our data confirm and extend previous studies supporting a role for PTH in the development of atherosclerotic disease.

  • 140.
    Hallberg, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, Julia
    Kurland, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Kahan, Thomas
    Malmqvist, Karin
    Öhman, K. Peter
    Nyström, Fredrik
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial2002Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 20, nr 10, s. 2089-2093Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The cytochrome P450 CYP2C9 enzyme (CYP2C9) metabolizes many clinically important drugs, for example, phenytoin, warfarin and the angiotensin II type 1 (AT(1)) receptor antagonists, losartan and irbesartan. Single nucleotide polymorphisms in the CYP2C9 gene result in the expression of three important variants, CYP2C9*1(wild-type), CYP2C9*2 and CYP2C9*3, the last two exhibiting reduced catalytic activity compared with the wild-type. The CYP2C9 genotype is known to determine sensitivity to and dose requirements for both warfarin and phenytoin, and also the rate of metabolism of losartan. However, its influence on clinical response to treatment with the AT(1) receptor antagonist, irbesartan, has not been investigated. OBJECTIVE: To determine whether the CYP2C9genotype influences the blood pressure-decreasing response to antihypertensive treatment with irbesartan. DESIGN AND METHODS: One hundred and two patients with essential hypertension and left ventricular hypertrophy were allocated randomly to groups to receive double-blind treatment with either irbesartan (n = 49) or the beta(1)-adrenergic receptor blocker, atenolol ( n= 53). Blood pressure was measured before and after 12 weeks of treatment. genotyping was performed using solid-phase minisequencing. RESULTS: The diastolic blood pressure (DBP) response differed in relation to the CYP2C9 genotype in patients given irbesartan: the reduction in patients with genotype CYP2C9*1/CYP2C9*1 (n = 33) was 7.5% and that with CYP2C9*1/CYP2C9*2 (n = 12) was 14.4% ( P= 0.036). A similar trend was seen for systolic blood pressure. In contrast, no relation was seen between the CYP2C9 genotype and blood pressure response to atenolol, a drug not metabolized via CYP2C9. CONCLUSIONS: The CYP2C9 genotype seems to predict the DBP response to irbesartan, but not to atenolol, in patients with essential hypertension.

  • 141.
    Hallberg, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Karlsson, Julia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kurland, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kahan, Thomas
    Malmqvist, Karin
    Öhman, K. Peter
    Nyström, Fredrik
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    B2 bradykinin receptor (B2BKR) polymorphism and change in left ventricular mass in response to antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial2003Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 21, nr 3, s. 621-4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Hypertension is associated with a number of adverse morphologic and functional changes in the cardiovascular system, including left ventricular (LV) hypertrophy. Studies have demonstrated that bradykinin, through the B2 bradykinin receptor (B2BKR), mediates important cardiovascular effects that may protect against LV hypertrophy. Recently, a +9/-9 exon 1 polymorphism of the B2BKR was shown to be strongly associated with LV growth response among normotensive males undergoing physical training. We aimed to clarify whether the processes found in exercise-induced LV growth in normotensive people also occur in pathological LV hypertrophy. DESIGN AND METHODS: We determined the B2BKR genotype of 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, included in a double-blind study to receive treatment for 48 weeks with either the angiotensin II type 1 (AT1) receptor antagonist irbesartan or the beta1-adrenoceptor antagonist atenolol. RESULTS: B2BKR +9/+9 genotypes responded poorly in LV mass regression, independent of blood pressure reduction or treatment, as compared to the other genotypes (adjusted mean change in LV mass index = -10.0 +/- 4.6 versus -21.6 +/- 2.2 g/m2, P = 0.03). CONCLUSIONS: Our results suggest an impact of the B2BKR polymorphism on LV mass regression during antihypertensive treatment.

  • 142.
    Hallberg, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kurland, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kahan, Thomas
    Malmqvist, Karin
    Öhman, Karl Peter
    Nyström, Fredrik
    Liljedahl, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy2003Ingår i: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 18, nr 3, s. 11-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Adipocyte-derived leucine aminopeptidase (ALAP) is a recently identified member of the M1 family of zinc-metallopeptidases and is thought to play a role in blood pressure control through inactivation of angiotensin II and/or generation of bradykinin. The enzyme seems to be particularly abundant in the heart. Recently, the Arg528-encoding allele of the ALAP gene was shown to be associated with essential hypertension.

    Methods

    We evaluated the influence of this polymorphism on the change in left ventricular mass index in 90 patients with essential hypertension and echocardiographically diagnosed left ventricular hypertrophy, randomised in a double-blind study to receive treatment with either the angiotensin II type I receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol for 48 weeks. Genyotyping was performed using minisequencing.

    Results

    After adjustment for potential covariates (blood pressure and left ventricular mass index at baseline, blood pressure change, age, sex, dose and added antihypertensive treatment), there was a marked difference between the Arg/Arg and Lys/Arg genotypes in patients treated with irbesartan; those with the Arg/Arg genotype responded on average with an almost two-fold greater regression of left ventricular mass index than patients with the Lys/Arg genotype (-30.1 g/m2 [3.6] vs -16.7 [4.5], p = 0.03).

    Conclusions

    The ALAP genotype seems to determine the degree of regression of left ventricular hypertrophy during antihypertensive treatment with the angiotensin II type I receptor antagonist irbesartan in patients with essential hypertension and left ventricular hypertrophy. This is the first report of a role for ALAP/aminopeptidases in left ventricular mass regulation, and suggests a new potential target for antihypertensive drugs.

  • 143. Hansen, T. W.
    et al.
    Thijs, L.
    Li, Y.
    Boggia, J.
    Liu, Y.
    Asayama, K.
    Kikuya, M.
    Björklund-Bodegård, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ohkubo, T.
    Jeppesen, J.
    Torp-Pedersen, C.
    Dolan, E.
    Kuznetsova, T.
    Stolarz-Skrzypek, K.
    Tikhonoff, V.
    Malyutina, S.
    Casiglia, E.
    Nikitin, Y.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sandoya, E.
    Kawecka-Jaszcz, K.
    Filipovsky, J.
    Imai, Y.
    Wang, J.
    O'Brien, E.
    Staessen, J. A.
    Ambulatory blood pressure monitoring for risk stratification in obese and non-obese subjects from 10 populations2014Ingår i: Journal of Human Hypertension, ISSN 0950-9240, E-ISSN 1476-5527, Vol. 28, nr 9, s. 535-542Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Overweight clusters with high blood pressure (BP), but the independent contribution of both risk factors remains insufficiently documented. In a prospective population study involving 8467 participants (mean age 54.6 years; 47.0% women) randomly recruited from 10 populations, we studied the contribution of body mass index (BMI) to risk over and beyond BP, taking advantage of the superiority of ambulatory over conventional BP. Over 10.6 years (median), 1271 participants (15.0%) died and 1092 (12.9%), 637 (7.5%) and 443 (5.2%) experienced a fatal or nonfatal cardiovascular, cardiac or cerebrovascular event. Adjusted for sex and age, low BMI (<20.7 kg m(-2)) predicted death (hazard ratio (HR) vs average risk, 1.52; P<0.0001) and high BMI (>= 30.9 kg m(-2)) predicted the cardiovascular end point (HR, 1.27; P = 0.006). With adjustments including 24-h systolic BP, these HRs were 1.50 (P <0.001) and 0.98 (P = 0.91), respectively. Across quartiles of the BMI distribution, 24-h and nighttime systolic BP predicted every end point (1.13 <= standardized HR <= 1.67; 0.046 <= P<0.0001). The interaction between systolic BP and BMI was nonsignificant (P >= 0.22). Excluding smokers removed the contribution of BMI categories to the prediction of mortality. In conclusion, BMI only adds to BP in risk stratification for mortality but not for cardiovascular outcomes. Smoking probably explains the association between increased mortality and low BMI.

  • 144.
    Hansen, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Söderberg, S.
    Hulthe, J.
    Wikström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Visceral adipose tissue, adiponectin levels and insulin resistance are related to atherosclerosis as assessed by whole-body magnetic resonance angiography in an elderly population2009Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 205, nr 1, s. 163-167Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The principal aim of this study was to determine whether the amount of visceral adipose tissue (VAT) is more related than subcutaneous adipose tissue (SAT) to atherosclerosis assessed by whole-body MRA (WBMRA). A further objective was to investigate whether traditional risk factors, inflammation, or adipokines could explain the hypothesized relationship between VAT and atherosclerosis. METHODS: Men and women aged 70 were recruited from the general population into the Prospective Investigation of The Vasculature in Uppsala Seniors (PIVUS) and 306 of them underwent WBMRA in a clinical 1.5-T scanner. The arterial tree was assessed for degree of stenosis or occlusion and a total atherosclerotic score (TAS) was established. Information on risk factors and BMI and on SAT and VAT, segmented on an axial MR scan was collected. Adiponectin, leptin, and high sensitive C-reactive protein (hsCRP) were measured in serum. HOMA index was used as a marker of insulin resistance. RESULTS: VAT was related to TAS independently of gender, total obesity (BMI), amount of SAT, hsCRP and also to the traditional risk factors included in the Framingham risk score (FRS) in an elderly population. Adiponectin or the HOMA insulin resistance, but not leptin or VAT, together with FRS was significantly related to TAS in a multiple censored regression model. CONCLUSION: Adiponectin attenuated the relationship between VAT and TAS, suggesting that adiponectin and insulin resistance is an important link between visceral adiposity and atherosclerosis.

  • 145.
    Hansen, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Total atherosclerotic burden measured by magnetic resonance imaging is related to five-year decline in cognitive function2018Ingår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, nr 3, s. 373-377Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The aim of this study was to explore whether total atherosclerotic burden is related to future decline in performance on cognitive tests.

    Methods: The total atherosclerotic burden (TAS) was assessed by whole‐body magnetic resonance angiography (WBMRA) in 305 subjects at age 70 in the study Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS). The mini‐mental state examination (MMSE) and trail making tests (TMT) A and B were evaluated at ages 75 and 80 in 190 of those subjects. No subject with a diagnosis of dementia was included in the sample.

    Results: MMSE did not change during the 5 years of follow‐up, while TMT A and B increased by 4 and 7 s, respectively. TAS at age 70 was significantly related to the individual change in TMT B (P<0·0001) between age 75 and 80, when adjusted for sex, education level, TMT B at age 75 and Framingham score at age 70. No such relationship was seen for the change in TMT A (P = 0·10). The relationship between TAS and the change in MMSE was of borderline significance (P = 0·025).

    Conclusion: A relationship was found between the total atherosclerotic burden and future decline in performance on TMT B, highlighting a role of global atherosclerosis in the cognitive decline seen during ageing.

  • 146.
    Hedman, Åsa K.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    Mendelson, Michael M.
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Boston, MA 02215 USA.;Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, 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..
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Joehanes, Roby
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.;Harvard Med Sch, Hebrew Senior Life, Boston, MA USA..
    Irvin, Marguerite R.
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA..
    Zhi, Degui
    Univ Alabama Birmingham, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA..
    Sandling, Johanna K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Yao, Chen
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA..
    Liu, Chunyu
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Dept Biosci, Boston, MA 02215 USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA..
    Liang, Liming
    Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Huan, Tianxiao
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA..
    McRae, Allan F.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Demissie, Serkalem
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Dept Biosci, Boston, MA 02215 USA..
    Shah, Sonia
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    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..
    Cupples, L. Adrienne
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Dept Biosci, Boston, MA 02215 USA..
    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, Saudi Arabia..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England..
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Krauss, Ronald M.
    Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA..
    Arnett, Donna K.
    Univ Kentucky, Coll Publ Hlth, Lexington, KY 40506 USA..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Levy, Daniel
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, 300 Pasteur Dr,Mail Code 5773, Stanford, CA 94305 USA..
    Epigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies2017Ingår i: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 10, nr 1, artikel-id UNSP e001487Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background- Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications. Methods and Results- To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals. We identified 193 CpGs associated with lipid levels in the discovery stage (P < 1.08E-07) and replicated 33 (at Bonferroni-corrected P < 0.05), including 25 novel CpGs not previously associated with lipids. Genes at lipid-associated CpGs were enriched in lipid and amino acid metabolism processes. A differentially methylated locus associated with triglyceridesand high-density lipoprotein cholesterol (HDL- C; cg27243685; P= 8.1E-26 and 9.3E-19) was associated with cis-expression of a reverse cholesterol transporter (ABCG1; P= 7.2E-28) and incident cardiovascular disease events (hazard ratio per SD increment, 1.38; 95% confidence interval, 1.15-1.66; P= 0.0007). We found significant cis-methylation quantitative trait loci at 64% of the 193 CpGs with an enrichment of signals from genome-wide association studies of lipid levels (P-TC = 0.004, PHDL-C = 0.008 and P-triglycerides = 0.00003) and coronary heart disease ( P= 0.0007). For example, genome-wide significant variants associated with low-density lipoprotein cholesterol and coronary heart disease at APOB were cis-methylation quantitative trait loci for a low-density lipoprotein cholesterol-related differentially methylated locus. Conclusions-We report novel associations of DNA methylation with lipid levels, describe epigenetic mechanisms related to previous genome-wide association studies discoveries, and provide evidence implicating epigenetic regulation of reverse cholesterol transport in blood in relation to occurrence of cardiovascular disease events.

  • 147.
    Hedman, Åsa K.
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Zilmer, Mihkel
    Univ Tartu, Inst Biomed & Translat Med, Dept Biochem, Ctr Excellence Genom & Translat Med, Tartu, Estonia..
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    DNA methylation patterns associated with oxidative stress in an ageing population2016Ingår i: BMC Medical Genomics, ISSN 1755-8794, E-ISSN 1755-8794, Vol. 9, artikel-id 72Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Oxidative stress has been related to type 2 diabetes (T2D) and cardiovascular disease (CVD), the leading global cause of death. Contributions of environmental factors such as oxidative stress on complex traits and disease may be partly mediated through changes in epigenetic marks (e.g. DNA methylation). Studies relating differential methylation with intermediate phenotypes and disease endpoints may be useful in identifying additional candidate genes and mechanisms involved in disease. Methods: To investigate the role of epigenetic variation in oxidative stress marker levels and subsequent development of CVD and T2D, we performed analyses of genome-wide DNA methylation in blood, ten markers of oxidative stress (total glutathione [TGSH], reduced glutathione [GSH], oxidised glutathione [GSSG], GSSG to GSH ratio, homocysteine [HCY], oxidised low-density lipoprotein (oxLDL), antibodies against oxLDL [OLAB], conjugated dienes [CD], baseline conjugated dienes [BCD]-LDL and total antioxidant capacity [TAOC]) and incident disease in up to 966 age-matched individuals. Results: In total, we found 66 cytosine-guanine (CpG) sites associated with one or more oxidative stress markers (false discovery rate [FDR] <0.05). These sites were enriched in regulatory regions of the genome. Genes annotated to CpG sites showed enrichment in annotation clusters relating to phospho-metabolism and proteins with pleckstrin domains. We investigated the contribution of oxidative stress-associated CpGs to development of cardiometabolic disease. Methylation variation at CpGs in the 3'-UTR of HIST1H4D (cg08170869; histone cluster 1, H4d) and in the body of DVL1 (cg03465880; dishevelled-1) were associated with incident T2D events during 10 years of follow-up (all permutation p-values < 0.01), indicating a role of epigenetic regulation in oxidative stress processes leading to development or progression of diabetes. Methylation QTL (meQTL) analysis showed significant associations with genetic sequence variants in cis at 28 (42%) of oxidative stress phenotype-associated sites (FDR < 0.05). Integrating cis-meQTLs with genotype-phenotype associations indicated that genetic effects on oxidative stress phenotype at one locus (cg07547695; BCL2L11) may be mediated through DNA methylation. Conclusions: In conclusion, we report novel associations of DNA methylation with oxidative stress, some of which also show evidence of a relation with T2D incidence.

  • 148.
    Helmersson, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Ridefelt, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Reference values for 34 frequently used laboratory tests in 80-year-old men and women2016Ingår i: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 92, s. 97-101Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Reference values are usually based on blood samples from healthy individuals in the age range 20-50 years. Most patients seeking health care are older than this reference population. Many reference intervals are age dependent and there is thus a need to have appropriate reference intervals also for elderly individuals.

    METHODS: We analyzed a group of frequently used laboratory tests in an 80-year-old population (n=531, 266 females and 265 males). The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines on the statistical treatment of reference values.

    RESULTS: Reference values are reported for serum alanine transaminase (ALT), albumin, alkaline phosphatase, pancreatic amylase, apolipoprotein A1, apolipoprotein B, apolipoprotein B/apolipoprotein A1 ratio, aspartate aminotransferase (AST), AST/ALT ratio, bilirubin, calcium, calprotectin, cholesterol, HDL-cholesterol, creatinine kinase (CK), creatinine, creatinine estimated GFR, C-reactive protein, cystatin C, cystatin C estimated GFR, gamma-glutamyltransferase (GGT), iron, iron saturation, lactate dehydrogenase (LDH), magnesium, phosphate, transferrin, triglycerides, urate, urea, zinc, hemoglobin, platelet count and white blood cell count. The upper reference limit for creatinine and urea was significantly increased while the lower limit for iron and albumin was decreased in this elderly population in comparison with the population in the Nordic Reference Interval Project (NORIP).

    CONCLUSIONS: Reference values calculated from the whole population and a subpopulation without cardiovascular disease showed strong concordance. Several of the reference interval limits were outside the 90% confidence interval of NORIP.

  • 149.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Carlsson, Axel C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ingelsson, Erik
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Urinary neutrophil gelatinase-associated lipocalin (NGAL) is associated with mortality in a community-based cohort of older Swedish men2013Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 227, nr 2, s. 408-413Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE

    Neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular kidney damage, neutrophil activation and possibly atherogenesis, however the prospective association between urinary NGAL (u-NGAL) and cardiovascular death in the community is not known.

    METHODS

    This study evaluates the association between urinary and serum NGAL and mortality in a Swedish population of 597 men aged 78 years. During the study (median follow-up 8.1 years) 261 men died, 90 of cardiovascular causes.

    RESULTS

    U-NGAL was associated with increased all-cause and cardiovascular mortality (HR 2.0 for quartile 4 vs. quartile 1, 95% CI 1.0-4.0, P < 0.05) in Cox regression models independently of cardiovascular risk factors, CRP and cystatin C estimated glomerular filtration rate (eGFRCysC) but not urinary Albumin (u-Alb). A combination of low eGFRCysC (≤60 mL/min), high u-Alb (≥3 mg/mmol Cr) and high u-NGAL (≥1.19 μg/mmol Cr) was associated with a 9-fold increased cardiovascular mortality (P < 0.001) and a 3-fold increased all-cause mortality (P < 0.001). Serum NGAL was associated with increased all-cause mortality risk independent of other cardiovascular risk factors (HR 1.4 for quartile 4 vs.1, 95% CI 1.0-1.9, P < 0.05) but not after adjustment with CRP, eGFRCysC or u-Alb.

    CONCLUSION

    This community study is the first to show that the tubular kidney biomarker u-NGAL associated with increased cardiovascular and all-cause mortality independent of cardiovascular risk factors and glomerular filtration. Additional research is needed to evaluate the utility of NGAL in clinical practice.

  • 150.
    Henriksson, Peter
    et al.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Qing, Lu
    Karolinska Univ Hosp, Div Clin Chem, Stockholm, Sweden.
    Freyschuss, Anna
    Karolinska Univ Hosp, Dept Med, Stockholm, Sweden.
    Microvascular capillary assessment in relation to forearm blood flow2019Ingår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 39, nr 5, s. 322-326Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To study whether vascular reactivity as assessed by the methods forearm blood flow (FBF) and postocclusive reactive hyperaemia (PRH) in the nail fold was related as a measure of endothelium-dependent vasodilation in the microcirculation. Methods Microvascular reactivity was assessed in forearm blood flow and in the nail fold by vital capillaroscopy of individual microvessels as postocclusive reactive hyperaemia. Vascular reactivity was assessed at baseline (n = 25) as well as after infusion of acetylcholine and of sodium nitroprusside (n = 13). We also performed a multivariate regression analysis to assess whether forearm blood flow or flow-mediated dilatation related to postocclusive reactive hyperaemia. Results This study showed a distinct microvascular response to both acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) during forearm blood flow assessment and postocclusive reactive hyperaemia assessment in the nail fold (n = 13). These changes were inversely related (r- = -0 center dot 57; P<0 center dot 05). Conclusions Forearm blood flow was inversely correlated to postocclusive reactive hyperaemia. Postocclusive reactive hyperaemia was shortened after infusion with both acetylcholine and sodium nitroprusside. This occurred in parallel with the expected increase in forearm blood flow, conceivably reflecting that both methods can be used to assess endothelium-dependent vasodilation in the microcirculation.

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