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  • 1.
    Balliu, Brunilda
    et al.
    Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA.
    Durrant, Matthew
    Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA.
    de Goede, Olivia
    Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA.
    Abell, Nathan
    Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA.
    Li, Xin
    Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA.
    Liu, Boxiang
    Stanford Univ, Dept Biol, Sch Med, Stanford, CA USA.
    Gloudemans, Michael J.
    Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA.
    Cook, Naomi L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
    Smith, Kevin S.
    Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA.
    Knowles, David A.
    New York Genome Ctr, New York, NY USA.
    Pala, Mauro
    Univ Sassari, Dipartimento Sci Biomed, Sassari, Italy.
    Cucca, Francesco
    Univ Sassari, Dipartimento Sci Biomed, Sassari, Italy.
    Schlessinger, David
    NIA, Lab Genet, Bethesda, MD USA.
    Jaiswal, Siddhartha
    Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA.
    Sabatti, Chiara
    Stanford Univ, Dept Biomed Data Sci, Sch Med, Stanford, CA USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Ingelsson, Erik
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dep Med, Stanford, CA USA; Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA USA; Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA USA.
    Montgomery, Stephen B.
    Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA; Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA.
    Genetic regulation of gene expression and splicing during a 10-year period of human aging2019In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 20, no 1, article id 230Article in journal (Refereed)
    Abstract [en]

    Background: Molecular and cellular changes are intrinsic to aging and age-related diseases. Prior cross-sectional studies have investigated the combined effects of age and genetics on gene expression and alternative splicing; however, there has been no long-term, longitudinal characterization of these molecular changes, especially in older age.

    Results: We perform RNA sequencing in whole blood from the same individuals at ages 70 and 80 to quantify how gene expression, alternative splicing, and their genetic regulation are altered during this 10-year period of advanced aging at a population and individual level. We observe that individuals are more similar to their own expression profiles later in life than profiles of other individuals their own age. We identify 1291 and 294 genes differentially expressed and alternatively spliced with age, as well as 529 genes with outlying individual trajectories. Further, we observe a strong correlation of genetic effects on expression and splicing between the two ages, with a small subset of tested genes showing a reduction in genetic associations with expression and splicing in older age.

    Conclusions: These findings demonstrate that, although the transcriptome and its genetic regulation is mostly stable late in life, a small subset of genes is dynamic and is characterized by a reduction in genetic regulation, most likely due to increasing environmental variance with age.

  • 2.
    Bao, Xue
    et al.
    Tianjin Med Univ, Nutr Epidemiol Inst, Tianjin, Peoples R China;Tianjin Med Univ, Sch Publ Hlth, Tianjin, Peoples R China;Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Borne, Yan
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Muhammad, Iram Faqir
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Nilsson, Jan
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Melander, Olle
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Niu, Kaijun
    Tianjin Med Univ, Nutr Epidemiol Inst, Tianjin, Peoples R China;Tianjin Med Univ, Sch Publ Hlth, Tianjin, Peoples R China.
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Engström, Gunnar
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus: the Malmö Diet and Cancer-Cardiovascular Cohort2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, no 1, p. 78-86Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Growth differentiation factor 15 (GDF-15) is an anti-inflammatory cytokine of the transforming growth factor- superfamily. Circulating levels of GDF-15 are associated with hyperglycaemia among people with obesity or diabetes, but longitudinal evidence on the association between GDF-15 levels and diabetes risk is scarce. Our aim was to explore whether circulating levels of GDF-15 at baseline are positively associated with future diabetes incidence in a middle-aged urban population.

    Methods: Between 1991 and 1994, baseline fasting plasma GDF-15 levels were measured in 4360 individuals without diabetes (mean age 57.45.96years, 38.6% men) who were participants in the Malmo Diet and Cancer-Cardiovascular Cohort. After a follow-up of 19.05.16years (mean +/- SD), Cox proportional hazards regression analysis was used for the study of the relationship between baseline GDF-15 and incident diabetes, with adjustment for established confounders. A sensitivity analysis included further adjustment for levels of C-reactive protein (CRP).

    Results: During the follow-up period, 621 individuals developed diabetes. The multivariate-adjusted HR for diabetes incidence was 1.43 (95% CI 1.11, 1.83; p for trend = 0.007) for the fourth compared with the first quartile of GDF-15, and was 1.17 (95% CI 1.07, 1.28; p<0.001) per SD increase of GDF-15. If participants were grouped according to baseline fasting glucose, the association between GDF-15 and diabetes risk was only evident in the group without impaired fasting glucose (n=3973). The association tended to be less significant with increasing age: multivariate-adjusted HRs for diabetes per SD increase of GDF-15 were 1.24 (95% CI 1.08, 1.42), 1.19 (95% CI 1.00, 1.41) and 1.04 (95% CI 0.89, 1.23) for participants aged 55, 56-60 (>55 and 60) and >60years, respectively. With adjustment for levels of CRP, the HR per SD increase of GDF-15 (1.21, 95% CI 1.09, 1.35) was significant (p=0.015), but the HR for the fourth compared with the first quartile of GDF-15 was not significant (HR 1.30; 95% CI 1.01, 1.67; p for trend = 0.061).

    Conclusions/interpretation: GDF-15 may be useful for identification of people with a risk of incident diabetes, especially if those people are 60years old.

  • 3.
    Beijer, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Nilsson, Peter M.
    SUS Malmö, Dept Clin Sci, Malmö, Sweden.
    Elmståhl, Sölve
    Lund Univ, Malmö Univ Hosp, Dept Hlth Sci, Div Geriatr Med, Malmö, Sweden.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Physical activity may compensate for prolonged TV time regarding pulse rate-a cross-sectional study2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 4, p. 247-254Article in journal (Refereed)
    Abstract [en]

    Background: Regular exercise reduces pulse rate, but it is less clear how prolonged sitting time affects pulse rate. Our hypothesis was that high physical activity could compensate for prolonged sitting time regarding the pulse rate.

    Methods: Regression analysis was performed on cross-sectional data including 47,457 men and women based on two Swedish cohort studies, EpiHealth (18–45 years) and LifeGene (45–75 years). Self-reported leisure time physical activity was given in five levels, from low (level 1) to vigorous (level 5), and television time was used as a proxy of sitting time.

    Results: A higher physical activity (level 4 compared to level 1) was associated with a lower pulse rate in middle-aged females (-2.7 beats per minute [bpm]; 95% CI -3.3 to -2.2) and males (-4.0 bpm; 95% CI -4.7 to -3.4). The relationship between physical activity and pulse rate was strongest in the young. A prolonged television time (3 h compared to 1 h per day) was associated with a slightly higher pulse rate in middle-aged females (+0.6 bpm; 95% CI +0.3 to +0.8) and males (+0.9 bpm; 95% CI +0.7 to +1.2). Among participants with a prolonged television time (3 h), those with a high physical activity (level 4) had a lower pulse rate compared to those with a low physical activity (level 1).

    Conclusions: A prolonged television time was associated with a high pulse rate, while high physical activity was associated with a low pulse rate. The results suggest that a high physical activity could compensate for a prolonged television time regarding pulse rate.

  • 4.
    Berglund, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Westerling, Ragnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Length of time periods in treatment effect descriptions and willingness to initiate preventive therapy: a randomised survey experiment2018In: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 18, article id 106Article in journal (Refereed)
    Abstract [en]

    Background Common measures used to describe preventive treatment effects today are proportional, i.e. they compare the proportions of events in relative or absolute terms, however they are not easily interpreted from the patient's perspective and different magnitudes do not seem to clearly discriminate between levels of effect presented to people. Methods In this randomised cross-sectional survey experiment, performed in a Swedish population-based sample (n=1041, response rate 58.6%), the respondents, aged between 40 and 75years were given information on a hypothetical preventive cardiovascular treatment. Respondents were randomised into groups in which the treatment was described as having the effect of delaying a heart attack for different periods of time (Delay of Event,DoE): 1month, 6months or 18months. Respondents were thereafter asked about their willingness to initiate such therapy, as well as questions about how they valued the proposed therapy. ResultsLonger DoE:s were associated with comparatively greater willingness to initiate treatment. The proportions accepting treatment were 81, 71 and 46% when postponement was 18months, 6months and 1month respectively. In adjusted binary logistic regression models the odds ratio for being willing to take therapy was 4.45 (95% CI 2.72-7.30) for a DoE of 6months, and 6.08 (95% CI 3.61-10.23) for a DoE of 18months compared with a DoE of 1month. Greater belief in the necessity of medical treatment increased the odds of being willing to initiate therapy. ConclusionsLay people's willingness to initiate preventive therapy was sensitive to the magnitude of the effect presented as DoE. The results indicate that DoE is a comprehensible effect measure, of potential value in shared clinical decision-making.

  • 5.
    Bixby, Honor
    et al.
    Imperial College London, London, UK.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Yngve, Agneta
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics.
    Ezzati, Majid
    Imperial College London, London, UK.
    Rising rural body-mass index is the main driver of the global obesity epidemic in adults2019In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 569, no 7755, p. 260-264Article in journal (Other academic)
    Abstract [en]

    Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.

  • 6.
    Cai, Gui-Hong
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Elmstahl, S.
    Lund Univ, Div Geriatr Med, Dept Hlth Sci, Lund, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Both weight at age 20 and weight gain have an impact on sleep disturbances later in life – results of the epihealth study2017In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 40, no Supplement 1, p. E195-E195Article in journal (Other academic)
  • 7.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    A framework for monitoring of new drugs in Sweden2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 46-50Article in journal (Refereed)
    Abstract [en]

    In order to monitor the net public health benefit of new drugs, especially in the light of recent stepwise approval approaches, there is a need to optimize real-time post-marketing evaluation of new drugs using data collected in routine care. Sweden, with its unique possibilities for observational research, can provide these data. We herein propose a framework for continuous monitoring of the effectiveness, safety, and cost-effectiveness of new drugs, using prospectively determined protocols designed in collaboration between all relevant stakeholders. We believe that this framework can be a useful tool for healthcare authorities and reimbursement agencies in the introduction of new drugs.

  • 8.
    Chróinín, Danielle Ní
    et al.
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Asplund, Kjell
    Umeå Univ Hosp, Dept Med, Umeå, Sweden.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Callaly, Elizabeth
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Cuadrado-Godia, Elisa
    Hosp del Mar IMIM, Dept Neurol, Barcelona, Spain.
    Diez-Tejedor, Exuperio
    Univ Autonoma Madrid, Dept Neurol, La Paz Univ Hosp, Madrid, Spain; Univ Autonoma Madrid, Stroke Ctr, La Paz Univ Hosp, Madrid, Spain.
    Di Napoli, Mario
    San Camillo deLellis Gen Hosp, Neurol Serv, Rieti, Italy; Ctr Cardiovasc Med & Cerebrovasc Dis Prevent, SMDN, Laquila, Italy .
    Engelter, Stefan T.
    Univ Basel Hosp, Dept Neurol, Basel, Switzerland.
    Furie, Karen L.
    Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Ctr Human Genet Res, Boston, MA USA.
    Giannopoulos, Sotirios
    Univ Ioannina, Sch Med, Ioannina, Greece.
    Gotto, Antonio M., Jr.
    Weill Cornell Med Coll, New York, NY USA.
    Hannon, Niamh
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Jonsson, Fredrik
    Umeå Univ Hosp, Dept Med, Umeå, Sweden.
    Kapral, Moira K.
    Toronto Gen Hosp, Inst Clin Evaluat Sci, Toronto, ON, Canada.
    Martí-Fàbregas, Joan
    Hosp Santa Creu & Sant Pau, Barcelona, Spain.
    Martínez-Sánchez, Patricia
    Univ Autonoma Madrid, Dept Neurol, La Paz Univ Hosp, Madrid, Spain; Univ Autonoma Madrid, Stroke Ctr, La Paz Univ Hosp, Madrid, Spain.
    Milionis, Haralampos J.
    Univ Ioannina, Sch Med, Ioannina, Greece.
    Montaner, Joan
    Autonomous Univ Barcelona, Hosp Vall dHebron, Barcelona, Spain; Autonomous Univ Barcelona, Vall dHebron Res Inst VHIR, Barcelona, Spain.
    Muscari, Antonio
    Univ Bologna, S Orsola Malpighi Hosp, Bologna, Italy.
    Pikija, Slaven
    Gen Hosp Varazdin, Varazhdin, Croatia.
    Probstfield, Jeffrey
    Univ Washington, Dept Med, Seattle, WA USA; Univ Washington, Dept Epidemiol, Seattle, WA USA.
    Rost, Natalia S.
    Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Ctr Human Genet Res, Boston, MA USA.
    Thrift, Amanda G.
    Monash Univ, Monash Med Ctr, Stroke & Ageing Res Ctr, Dept Med, Clayton, Vic, Australia; Natl Stroke Res Inst, Heidelberg, Vic, Australia.
    Vemmos, Konstantinos
    Univ Athens, Dept Therapeut, Alexandra Hosp, Athens, Greece.
    Kelly, Peter J.
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Statin Therapy and Outcome After Ischemic Stroke: Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials2013In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 44, no 2, p. 448-456Article, review/survey (Refereed)
    Abstract [en]

    Background and Purpose: Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke.

    Methods: The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (≤72 hours after stroke), and (2) thrombolysis-treated patients.

    Results: The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29–1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9–1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62–0.82; P<0.001) and 1 year (OR, 0.80; 95% CI, 0.67–0.95; P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0–2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02–1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90–1.44; 4012 patients).

    Conclusion: In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. Randomized trials of statin therapy in acute ischemic stroke are needed.

  • 9.
    Diamanti, Klev
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Visvanathar, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Cavalli, Marco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pan, Gang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Kumar, Chanchal
    Translational Science & Experimental Medicine, Early Cardiovascular, Renal and Metabolism, R&D BioPharmaceuticals, AstraZeneca; Karolinska Institute/AstraZeneca Integrated CardioMetabolic Centre (KI/AZ ICMC), Department of Medicine.
    Stanko, Stanko
    Pharmaceutical Technology & Development, AstraZeneca AB; Department of Medicine, Sahlgrenska University Hospital, Gothenburg.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wadelius, Claes
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Komorowski, Jan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Integration of whole-body PET/MRI with non-targeted metabolomics provides new insights into insulin sensitivity of various tissuesManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Alteration of various metabolites has been linked to type 2 diabetes (T2D) and insulin resistance. However, identifying significant associations between metabolites and tissue-specific alterations is challenging and requires a multi-omics approach. In this study, we aimed at discovering associations of metabolites from subcutaneous adipose tissue (SAT) and plasma with the volume, the fat fraction (FF) and the insulin sensitivity (Ki) of specific tissues using [18F]FDG PET/MRI.

    Materials and Methods: In a cohort of 42 subjects with different levels of glucose tolerance (normal, prediabetes and T2D) matched for age and body-mass-index (BMI) we calculated associations between parameters of whole-body FDG PET/MRI during clamp and non-targeted metabolomics profiling for SAT and blood plasma. We also used a rule-based classifier to identify a large collection of prevalent patterns of co-dependent metabolites that characterize non-diabetes (ND) and T2D.

    Results: The plasma metabolomics profiling revealed that hepatic fat content was positively associated with tyrosine, and negatively associated with lysoPC(P-16:0). Ki in visceral adipose tissue (VAT) and SAT, was positively associated with several species of lysophospholipids while the opposite applied to branched-chain amino acids (BCAA) and their intermediates. The adipose tissue metabolomics revealed a positive association between non-esterified fatty acids and, VAT and liver Ki. On the contrary, bile acids and carnitines in adipose tissue were inversely associated with VAT Ki. Finally, we presented a transparent machine-learning model that predicted ND or T2D in “unseen” data with an accuracy of 78%.

    Conclusions: Novel associations of several metabolites from SAT and plasma with the FF, volume and insulin senstivity of various tissues throughout the body were discovered using PET/MRI and a new integrative multi-omics approach. A promising computational model that predicted ND and T2D with high certainty, suggested novel non-linear interdependencies of metabolites.

  • 10.
    Dumanski, Jan P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab. Faculty of Pharmacy, Medical University of Gdansk, Poland.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Forsberg, Lars A.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Beijer Laboratory of Genome Research, Uppsala University.
    Loss of Chromosome Y in Leukocytes and Major Cardiovascular Events2017In: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 10, no 4Article in journal (Other academic)
  • 11.
    Dunder, Linda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lejonklou, Margareta Halin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Urinary bisphenol A and serum lipids: a meta-analysis of six NHANES examination cycles (2003-2014)2019In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 73, no 11, p. 1012-1019Article in journal (Refereed)
    Abstract [en]

    Background: Mounting evidence from both experimental and epidemiological studies suggest that exposure to the endocrine disruptor bisphenol A (BPA) has a role in metabolic disorders. The aim of the present study was to assess whether urinary BPA concentrations were associated with dyslipidaemia in children (<= 17 years old) and adults (>= 18 years old) by performing a meta-analysis of data from six cycles (2003-2014) in the National Health and Nutrition Examination Survey (NHANES).

    Methods: We conducted a meta-analysis of data from 4604 children and 10 989 adult participants who were part of a substudy of urinary BPA measurements from six NHANES cycles from 2003 to 2014. Linear regression models conducted in each cycle were used to perform a meta-analysis to investigate associations between urinary BPA and serum levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides (TG) and apolipoprotein B (ApoB).

    Results: The meta-analysis did not disclose any significant associations between urinary BPA concentrations and LDL-C, HDL-C, TC, TG and ApoB in children. In adults, the meta-analysis revealed negative regression coefficients for all five lipid variables. However, no associations were significant following Bonferroni correction for multiple tests.

    Conclusions: In the present meta-analysis of cross-sectional data from NHANES, no associations were found between urinary BPA and the five different lipid variables when investigated in both children and adults. However, considering the cross-sectional nature of the present study, results should be clarified in carefully designed longitudinal cohort studies with repeated BPA measurements.

  • 12.
    Eriksson, Hanna
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Wirdefeldt, Karin
    Karolinska Inst, Med Epidemiol & Biostat, Solna, Sweden;Karolinska Univ Hosp, Dept Clin Neurosci, Stockholm, Sweden.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Zelano, Johan
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Family history increases the risk of late seizures after stroke2019In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 93, no 21, p. E1964-E1970Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the association between a family history of epilepsy and risk of late poststroke seizures (LPS).

    Methods: This register-based cohort study was based on adult patients from the Swedish Stroke Register (Riksstroke) with stroke from 2001 to 2012 and no prior epilepsy. LPS (>7 days after stroke) and epilepsy were ascertained in cases and in their first-degree biological relatives by cross-referencing Riksstroke, the Multi-Generation Register, and the National Patient Register.

    Results: Of 86,550 patients with stroke, a family history of epilepsy was detected in 7,433 (8.6%), and LPS (>7 days after stroke) occurred in 7,307 (8.4%). The survival-adjusted risk of LPS was higher in patients with compared to those without a family history of epilepsy: 6.8% (95% confidence interval [CI] 6.2%-7.4%) vs 5.9% (95% CI 5.7%-6.1%) at 2 years and 9.5% (95% CI 8.7%-10.3%) vs 8.2% (95% CI 8.0%-8.4%) at 5 years. In a Cox model adjusted for age, sex, and stroke type, the hazard ratio (HR) for LPS in patients with stroke with >= 1 relative with epilepsy was 1.18 (95% CI 1.09-1.28). The increased HR remained significant with adjustments for stroke severity and in multiple sensitivity analyses. A higher risk for patients with stroke with >1 relative with epilepsy was also seen but was not significant in all Cox models.

    Conclusions: Although stroke characteristics remain the most important risk factors for LPS, having a first-degree relative with epilepsy also increases the risk in a multivariate analysis. The findings highlight the need for family history assessment in patients with stroke and the need for future studies on genetic vulnerability and environmental factors that may aid in the identification of at-risk individuals.

  • 13.
    Fellström, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Soveri, Inga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Wu, Ping-Hsun
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Thulin, Måns
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Ärnlöv, Johan
    Dalarna Univ, Dept Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females2020In: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 40, no 2, p. 71-74Article in journal (Refereed)
    Abstract [en]

    There exists a close relationship between cardiovascular diseases and chronic kidney disease. Apolipoprotein A1 and high-density lipoprotein (HDL) cholesterol are widely used as cardiovascular risk markers but they also have anti-inflammatory properties. The aim of this study was to investigate any associations between HDL levels and cytokine levels in urine. We randomly selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The samples were analyzed with 2 multiplex assays, Multiplex Inflammation I and Cardiovascular II kits (Olink Bioscience, Uppsala, Sweden). We analyzed the correlations between 158 cytokines in urine with apolipoprotein A1, HDL cholesterol, apolipoprotein B, and low-density lipoprotein cholesterol. There were strong correlations for apolipoprotein A1 and HDL cholesterol with individual cytokines. After adjustment for multiplicity testing, there were 33 significant correlations between apolipoprotein A1 and cytokine levels and 14 of these were also significantly correlated with HDL cholesterol. The strongest associations were observed for IL-1 alpha, SPON2, RAGE, PAR-1, TRAIL-R2, IL-4RA, TNFRSF11A, and SCF. A total of 28 out of 33 correlations were negative, indicating a negative relationship between apolipoprotein A1 and urinary cytokines. The study shows a negative correlation between apolipoprotein A1 and HDL cholesterol and urinary cytokine levels. The finding is in agreement with the anti-inflammatory properties of HDL.

  • 14.
    Feo, Rebecca
    et al.
    Univ Adelaide, Adelaide Nursing Sch, Adelaide, SA, Australia;Flinders Univ S Australia, Coll Nursing & Hlth Sci, Adelaide, SA, Australia.
    Donnelly, Frank
    Univ Adelaide, Adelaide Nursing Sch, Adelaide, SA, Australia.
    Muntlin Athlin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Jangland, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Providing high-quality fundamental care for patients with acute abdominal pain: A qualitative study of patients' experiences in acute care2019In: Journal of Health Organisation & Management, ISSN 1477-7266, E-ISSN 1758-7247, Vol. 33, no 1, p. 110-123Article in journal (Refereed)
    Abstract [en]

    Purpose Globally, acute abdominal pain (AAP) is one of the most common reasons for emergency admissions, yet little is known about how this patient group experiences the delivery of fundamental care across the acute care delivery chain. The purpose of this paper is to describe how patients with AAP experienced fundamental care across their acute care presentation, and to explicate the health professional behaviours, reported by patients, that contributed to their positive experiences. Design/methodology/approach A qualitative descriptive study, using repeated reflective interviews, was analysed thematically (n=10 patients). Findings Two themes were identified: developing genuine, caring relationships with health professionals and being informed about one's care. Patients reported that health professionals established genuine professional-patient relationships despite the busy care environment but perceived this environment as impeding information-provision. Patients were typically accepting of a lack of information, whereas poor professional-patient relationships were seen as inexcusable.

  • 15.
    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 University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    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 outcomes2018In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 5141Article in journal (Refereed)
    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.

  • 16.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    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 cohorts2019In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 25, no 6, p. 911-919Article in journal (Refereed)
    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.

  • 17.
    Hansen, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nilsson, M.
    Karolinska Inst, CLINTEC, Div Surg, Stockholm, Sweden;Karolinska Univ Hosp, Dept Upper Abdominal Surg, Div Canc, Stockholm, Sweden.
    Lindholm, Daniel P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Hedberg, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Normal radiological lymph node appearance in the thorax2019In: Diseases of the esophagus, ISSN 1120-8694, E-ISSN 1442-2050, Vol. 32, no 10, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Modern treatment of esophageal cancer is multimodal and highly dependent on a detailed diagnostic assessment of clinical stage, which includes nodal stage. Clinical appraisal of nodal stage is highly dependent on knowledge of normal radiological appearance, information of which is scarce. We aimed to describe lymph node appearance on computed tomography (CT) investigations in a randomly selected cohort of healthy subjects. In a sample of the Swedish Cardiopulmonary bioimage study, which investigates a sample of the Swedish population aged 50-64 years, the CT scans of 426 subjects were studied in detail concerning intrathoracic node stations relevant in clinical staging of esophageal cancer. With stratification for sex, the short axis of visible lymph nodes was measured and the distribution of lymph node sizes was calculated as well as proportion of patients with visible nodes above 5 and 10 millimeters for each station. Probability of having any lymph node station above 5 and 10 millimeters was calculated with a logistic regression model adjusted for age and sex. In the 214 men (aged: 57.3 +/- 4.1 years) and 212 women (aged: 57.8 +/- 4.4 years) included in this study, a total of 309 (72.5%) had a lymph node with a short axis of 5 mm or above was seen in at least one of the node stations investigated. When using 10 mm as a cutoff, nodes were visible in 29 (6.81%) of the subjects. Men had higher odds of having any lymph node with short axis 5 mm or above (OR 3.03 95% CI 1.89-4.85, P < 0.001) as well as 10 mm or above (OR 2.31 95% CI 1.02-5.23, P = 0.044) compared to women. Higher age was not associated with propensity for lymph nodes above 5 or 10 millimeters in this sample. We conclude that, in a randomly selected cohort of patients between 50 and 64 years, almost 10% of the men and 4% of the women had lymph nodes above 10 millimeters, most frequently in the subcarinal station (station 107). More than half of the patients had nodes above 5 millimeters on CT and men were much more prone to have this finding. The probability of finding lymph nodes in specific stations relevant of esophageal cancer is now described.

  • 18.
    Henriksson, Peter
    et al.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    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 flow2019In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 39, no 5, p. 322-326Article in journal (Refereed)
    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.

  • 19.
    Hober, Andreas
    et al.
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden;KTH Royal Inst Technol, Dept Prot Sci, Stockholm, Sweden.
    Edfors, Fredrik
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden;KTH Royal Inst Technol, Dept Prot Sci, Stockholm, Sweden.
    Ryaboshapkina, Maria
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Malmqvist, Jonas
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Rosengren, Louise
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Percy, Andrew J.
    Cambridge Isotope Labs Inc, Dept Applicat Dev, Tewksbury, MA 01876 USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Forsström, Björn
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden;KTH Royal Inst Technol, Dept Prot Sci, Stockholm, Sweden.
    Uhlen, Mathias
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden;KTH Royal Inst Technol, Dept Prot Sci, Stockholm, Sweden.
    Oscarsson, Jan
    AstraZeneca, Global Med Dev Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Miliotis, Tasso
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Absolute Quantification of Apolipoproteins Following Treatment with Omega-3 Carboxylic Acids and Fenofibrate Using a High Precision Stable Isotope-labeled Recombinant Protein Fragments Based SRM Assay2019In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 18, no 12, p. 2433-2446Article in journal (Refereed)
    Abstract [en]

    Stable isotope-labeled standard (SIS) peptides are used as internal standards in targeted proteomics to provide robust protein quantification, which is required in clinical settings. However, SIS peptides are typically added post trypsin digestion and, as the digestion efficiency can vary significantly between peptides within a protein, the accuracy and precision of the assay may be compromised. These drawbacks can be remedied by a new class of internal standards introduced by the Human Protein Atlas project, which are based on SIS recombinant protein fragments called SIS PrESTs. SIS PrESTs are added initially to the sample and SIS peptides are released on trypsin digestion. The SIS PrEST technology is promising for absolute quantification of protein biomarkers but has not previously been evaluated in a clinical setting. An automated and scalable solid phase extraction workflow for desalting and enrichment of plasma digests was established enabling simultaneous preparation of up to 96 samples. Robust high-precision quantification of 13 apolipoproteins was achieved using a novel multiplex SIS PrEST-based LC-SRM/MS Tier 2 assay in non-depleted human plasma. The assay exhibited inter-day coefficients of variation between 1.5% and 14.5% (median = 3.5%) and was subsequently used to investigate the effects of omega-3 carboxylic acids (OM3-CA) and fenofibrate on these 13 apolipoproteins in human plasma samples from a randomized placebo-controlled trial, EFFECT I (NCT02354976). No significant changes were observed in the OM3-CA arm, whereas treatment with fenofibrate significantly increased apoAII and reduced apoB, apoCI, apoE and apoCIV levels. The reduction in apoCIV following fenofibrate treatment is a novel finding. The study demonstrates that SIS PrESTs can facilitate the generation of robust multiplexed biomarker Tier 2 assays for absolute quantification of proteins in clinical studies. Applications of LC-SRM in clinical research are still limited. SIS PrEST are a novel class of standards added prior to trypsinization. We have developed a semi-automated sample preparation workflow and a SIS PrEST LC-SRM/MS Tier 2 assay for absolute quantification of 13 apolipoproteins in human plasma and applied it on clinical samples from the EFFECT I study. We demonstrate, for the first time, that SIS PrEST can be applied for exploratory biomarker research in clinical settings and capture drug effects.

  • 20.
    Jangland, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Teodorsson, Therese
    Hoglandssjukhuset Eksjo, Dept Surg, Eksjo, Sweden.
    Molander, Karin
    Sundsvall Hosp, Dept Surg, Sundsvall, Sweden.
    Muntlin Athlin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Univ Adelaide, Adelaide Nursing Sch, Adelaide, SA, Australia.
    Inadequate environment, resources, and values lead to missed nursing care: A focused ethnographic study on the surgical ward using the Fundamentals of Care framework2018In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 27, no 11-12, p. 2311-2321Article in journal (Refereed)
    Abstract [en]

    AIMS AND OBJECTIVES: The purpose was to explore the delivery of care from the perspective of patients with acute abdominal pain focusing on the contextual factors at system level using the Fundamentals of Care framework.

    BACKGROUND: The Fundamentals of Care framework describes several contextual and systemic factors that can impact the delivery of care. To deliver high- quality, person-centred care it is important to understand how these factors affect patients' experiences and care needs.

    DESIGN: A focused ethnographic approach.

    METHOD: A total of 20 observations were performed on two surgical wards at a Swedish university hospital. Data were collected using participant observation and informal interviews and analysed using deductive content analysis.

    RESULTS: The findings, presented in four categories, reflect the value patients place on the caring relationship and a friendly atmosphere on the ward. Patients had concerns about the environment, particularly the high-tempo culture on the ward and its impact on their integrity, rest and sleep, access to information and planning, and need for support in addressing their existential thoughts. The observers also noted that missed nursing care had serious consequences for patient safety.

    CONCLUSION: Patients with acute abdominal pain were cared for in the high-tempo culture of a surgical ward with limited resources, unclear leadership, and challenges to patients' safety. The findings highlight the crucial importance of prioritizing and valuing the patients' fundamental care needs for recovery.

    RELEVANCE TO CLINICAL PRACTICE: Nursing leaders and nurses need to take the lead to re-conceptualize the value of fundamental care in the acute care setting. To improve clinical practice the value of fundamentals of care must be addressed regardless of patient's clinical condition. Providing a caring relationship is paramount to ensure a positive impact on patient's well-being and recovery.

  • 21. Justice, Anne E.
    et al.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindgren, Cecilia M.
    Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution2019In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 3, p. 452-469Article in journal (Refereed)
    Abstract [en]

    Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.

  • 22.
    Kanukula, Raju
    et al.
    George Inst Global Hlth, Hyderabad, India.
    Esam, Hariprasad
    George Inst Global Hlth, Hyderabad, India.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Rodgers, Anthony
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.
    Salam, Abdul
    Univ New South Wales, George Inst Global Hlth, Hyderabad, India.
    Does Co-administration of Antihypertensive Drugs and Statins Alter Their Efficacy and Safety?: A Systematic Review and Meta-analysis of Randomized Controlled Trials2019In: Journal of Cardiovascular Pharmacology, ISSN 0160-2446, E-ISSN 1533-4023, Vol. 73, no 6, p. 352-358Article, review/survey (Refereed)
    Abstract [en]

    Antihypertensive drugs (AHTDs) and statins are frequently administered together, but there is uncertainty on whether the presence of one affects the main effects of the other. This systematic review and meta-analysis assessed the effects of coadministered AHTDs and statins on blood pressure (BP) and cholesterol. MEDLINE, Cochrane Central Register of Controlled Trials and drug regulatory agency websites were searched, until January 2018. Twelve double-blind randomized controlled trials that allocated adults with or without hypertension and/or hyperlipidemia (n = 4434) to fixed doses of AHTD alone, statin alone and both drugs together, for >= 4 weeks, were included. BP lowering was similar with AHTD + statin compared with AHTD alone [systolic BP -0.1 mm Hg, 95% confidence interval (CI), -1.0 to 0.8, and diastolic BP -1.0 mm Hg, 95% CI, -2.3 to -0.2]. AHTD + statin compared with statin alone resulted in small reduction in low-density lipoprotein cholesterol (-3.9 mg/dL, 95% CI, -6.1 to -1.7), and this effect was largely associated with co-administration of amlodipine and atorvastatin or rosuvastatin. There was no difference in safety outcomes. Overall, it can be concluded that there is no clinically important difference in the effects of AHTDs and statins whether used separately or together for reduction in BP and lowdensity lipoprotein cholesterol.

  • 23.
    Kaptoge, Stephen
    et al.
    Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Di Angelantonio, Emanuele
    Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England.
    World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions2019In: The Lancet Global Health, E-ISSN 2214-109X, Vol. 7, no 10, p. E1332-E1345Article in journal (Refereed)
    Abstract [en]

    Background: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions.

    Methods: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40–80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance.

    Findings: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629–0·741) to 0·833 (0·783–0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40–64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt.

    Interpretation: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide.

    Funding: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research.

  • 24.
    Karasik, David
    et al.
    Hebrew Senior Life Inst Aging Res, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA;Bar Ilan Univ, Azrieli Fac Med, Safed, Israel.
    Zillikens, M. Carola
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands.
    Hsu, Yi-Hsiang
    Hebrew Senior Life Inst Aging Res, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA 02115 USA;Harvard Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Boston, MA USA.
    Aghdassi, Ali
    Ernst Moritz Arndt Univ Greifswald, Dept Med A, Greifswald, Germany.
    Akesson, Kristina
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Barroso, Ines
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England;NIHR Cambridge Biomed Res Ctr, Cambridge, England;Univ Cambridge, Metab Res Labs, Inst Metab Sci, Addenbrookes Hosp, Cambridge, England.
    Bennett, David A.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
    Bertram, Lars
    Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt, Lubeck, Germany.
    Bochud, Murielle
    Lausanne Univ Hosp, Univ Inst Social & Prevent Med, Lausanne, Switzerland.
    Borecki, Ingrid B.
    Washington Univ, Dept Genet, Div Stat Gen, Sch Med, St Louis, MO 63110 USA;Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
    Broer, Linda
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Buchman, Aron S.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Teviot Pl, Edinburgh, Midlothian, Scotland.
    Campos-Obando, Natalia
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Cauley, Jane A.
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
    Cawthon, Peggy M.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
    Chambers, John C.
    Ealing Hosp NHS Trust, Cardiol, London, England;Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England;Imperial Coll Healthcare NHS Trust, London, England;Royal Brompton & Harefield NHS Fdn Trust, NIHR Cardiovasc Biomed Res Unit, London, England;Imperial Coll London, London, England.
    Chen, Zhao
    Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA.
    Cho, Nam H.
    Ajou Univ, Sch Med, Dept Prevent Med, Suwon, South Korea.
    Choi, Hyung Jin
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea;Seoul Natl Univ, Coll Med, Neurosci Res Inst, Dept Anat & Cell Biol, Seoul, South Korea;Seoul Natl Univ, Wide River Inst Immunol, Hongcheon, South Korea.
    Chou, Wen-Chi
    Hebrew Senior Life Inst Aging Res, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA;Broad Inst, Cambridge, MA USA.
    Cummings, Steven R.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
    de Groot, Lisette C. P. G. M.
    Columbia Univ, Med Ctr, Ctr Translat & Computat Neuroimmunol Neurol, New York, NY USA.
    De Jager, Phillip L.
    Broad Inst, Cell Circuits Program, Cambridge, MA USA;Free Univ Berlin, Humboldt Univ Berlin, Charite Univ Med Berlin, Berlin, Germany.
    Demuth, Ilja
    Berlin Inst Hlth, Berlin, Germany;Wageningen Univ, Div Human Nutr, AFSG, Wageningen, Netherlands.
    Diatchenko, Luda
    Univ North Carolina Chapel Hill, Sch Dent, Reg Ctr Neurosensory Disorders, Chapel Hill, NC USA;McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ, Canada.
    Econs, Michael J.
    Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA;Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
    Eiriksdottir, Gudny
    Iceland Heart Assoc Holtasmari, Kopavogur, Iceland.
    Enneman, Anke W.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Eriksson, Joel
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Eriksson, Johan G.
    Natl Inst Hlth & Welfare, Helsinki, Finland;Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland;Helsinki Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland;Folkhalsan Res Ctr, Helsinki, Finland.
    Estrada, Karol
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Biogen Inc, Translat Biol, 14 Cambridge Ctr, Cambridge, MA 02142 USA.
    Evans, Daniel S.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
    Feitosa, Mary F.
    Washington Univ, Dept Genet, Div Stat Gen, Sch Med, St Louis, MO 63110 USA.
    Fu, Mao
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA.
    Gieger, Christian
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany.
    Grallert, Harald
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany;Helmholtz Zentrum Munchen, CCG Type 2 Diabet, Neuherberg, Germany;German Ctr Diabet Res, Neuherberg, Germany.
    Gudnason, Vilmundur
    Iceland Heart Assoc Holtasmari, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Lenore, Launer J.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA.
    Hayward, Caroline
    Univ Edinburgh, MRC Human Genet Unit, IGMM, Edinburgh, Midlothian, Scotland.
    Hofman, Albert
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands.
    Homuth, Georg
    Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany.
    Huffman, Kim M.
    Duke Univ, Sch Med, Dept Med, Duke Mol Physiol Inst, Durham, NC 27706 USA;Duke Univ, Sch Med, Dept Med, Div Rheumatol, Durham, NC 27706 USA.
    Husted, Lise B.
    Aarhus Univ Hosp, Endocrinol & Internal Med, Aarhus, Denmark.
    Illig, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Hannover Med Sch, Dept Human Genet, Hannover, Germany.
    Ingelsson, Erik
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA USA.
    Ittermann, Till
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
    Jansson, John-Olov
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, Gothenburg, Sweden.
    Johnson, Toby
    Lausanne Univ Hosp, Univ Inst Social & Prevent Med, Lausanne, Switzerland;Univ Lausanne, Dept Med Genet, Lausanne, Switzerland;Swiss Inst Bioinformat, Lausanne, Switzerland.
    Biffar, Reiner
    Ernst Moritz Arndt Univ Greifswald, Dept Prosthet Dent Gerodontol & Biomat, Ctr Oral Hlth, Greifswald, Germany.
    Jordan, Joanne M.
    Univ North Carolina Chapel Hill, Thurston Arthrit Res Ctr, Chapel Hill, NC USA.
    Jula, Antti
    Natl Inst Hlth & Welfare, Helsinki, Finland.
    Karlsson, Magnus
    Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
    Kilpelainen, Tuomas O.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge, England;Univ Copenhagen, Fac Hlth & Med Sci, Sect Metabol Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark;Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY USA.
    Klopp, Norman
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany.
    Kloth, Jacqueline S. L.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Koller, Daniel L.
    Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA;Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
    Kooner, Jaspal S.
    Ealing Hosp NHS Trust, Cardiol, London, England;Imperial Coll Healthcare NHS Trust, London, England;Imperial Coll London, Hammersmith Hosp, Natl Heart & Lung Inst Cardiovasc Sci, Fac Med, Hammersmith Campus, London, England.
    Kraus, William E.
    Duke Univ, Sch Med, Dept Med, Duke Mol Physiol Inst, Durham, NC USA;Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC USA.
    Kritchevsky, Stephen
    Wake Forest Sch Med, Sticht Ctr Hlth Aging & Alzheimers Prevent, Winston Salem, NC USA.
    Kutalik, Zoltan
    Lausanne Univ Hosp, Univ Inst Social & Prevent Med, Lausanne, Switzerland;Helmholtz Zentrum Munchen, CCG Nutrigen & Type 2 Diabet, Neuherberg, Germany;Swiss Inst Bioinformat, Lausanne, Switzerland.
    Kuulasmaa, Teemu
    Univ Eastern Finland, Dept Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Kuusisto, Johanna
    Univ Eastern Finland, Dept Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Laakso, Markku
    Univ Eastern Finland, Dept Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Lahti, Jari
    Univ Helsinki, Helsinki Collegium Adv Studies, Helsinki, Finland.
    Lang, Thomas
    UC San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA USA;UC San Francisco, Sch Dent, San Francisco, CA USA.
    Langdahl, Bente L.
    Aarhus Univ Hosp, Endocrinol & Internal Med, Aarhus, Denmark.
    Lerch, Markus M.
    Ernst Moritz Arndt Univ Greifswald, Dept Med A, Greifswald, Germany.
    Lewis, Joshua R.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia;Univ Sydney, Sydney Med Sch, Sch Publ Hlth, Childrens Hosp Westmead,Ctr Kidney Res, Sydney, NSW, Australia.
    Lill, Christina
    Univ Lubeck, Inst Neurogenet, Lubeck, Germany.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindgren, Cecilia
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Liu, Yongmei
    Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
    Livshits, Gregory
    Tel Aviv Univ, Dept Anat & Anthropol, Sackler Fac Med, Tel Aviv, Israel;Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London, England.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY USA;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Inst Child Hlth & Dev, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Genet Obes & Related Traits Program, New York, NY 10029 USA.
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, Gothenburg, Sweden.
    Luan, Jian'an
    Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY USA.
    Luben, Robert N.
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metabol Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
    Malkin, Ida
    Tel Aviv Univ, Dept Anat & Anthropol, Sackler Fac Med, Tel Aviv, Israel.
    McGuigan, Fiona E.
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden.
    Medina-Gomez, Carolina
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, MRI, Munich, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden.
    Mitchell, Braxton D.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA;Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Liverpool, Inst Translat Med, Liverpool, Merseyside, England.
    Mosekilde, Leif
    Aarhus Univ Hosp, Endocrinol & Internal Med, Aarhus, Denmark.
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Newman, Anne B.
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
    O'Connell, Jeffery R.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA.
    Oostra, Ben A.
    Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands;Ctr Med Syst Biol & Netherlands Consortium H, Leiden, Netherlands.
    Orwoll, Eric S.
    Oregon Hlth & Sci Univ, Portland, OR USA.
    Palotie, Aarno
    Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland;Univ Helsinki, Dept Med Genet, Helsinki, Finland;Univ Cent Hosp, Helsinki, Finland.
    Peacock, Munro
    Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA;Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
    Perola, Markus
    Natl Inst Hlth & Welfare, Helsinki, Finland;Univ Helsinki, Inst Mol Med, Helsinki, Finland;Diabet & Obes Res Program, Helsinki, Finland;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Peters, Annette
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.
    Prince, Richard L.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia;Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Perth, WA, Australia.
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente, Washington Hlth Res Inst, Seattle, WA USA.
    Raikkonen, Katri
    Univ Helsinki, Dept Psychol & Logoped, Helsinki, Finland.
    Ralston, Stuart H.
    Harvard Med Sch, Boston, MA 02115 USA;Western Gen Hosp, MRC Inst Genet & Mol Med, Mol Med Ctr, Edinburgh, Midlothian, Scotland.
    Ripatti, Samuli
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland;Univ Helsinki, Hjelt Inst, Helsinki, Finland.
    Rivadeneira, Fernando
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Robbins, John A.
    Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA.
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA.
    Rudan, Igor
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
    Salomaa, Veikko
    Natl Inst Hlth & Welfare, Helsinki, Finland.
    Satterfield, Suzanne
    Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
    Schipf, Sabine
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
    Shin, Chan Soo
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea.
    Smith, Albert V.
    Iceland Heart Assoc Holtasmari, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Smith, Shad B.
    Duke Univ, Dept Anesthesiol, Ctr Translat Pain Med, Durham, NC USA.
    Soranzo, Nicole
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England.
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London, England.
    Stancakova, Alena
    Univ Eastern Finland, Dept Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Stefansson, Kari
    Univ Iceland, Fac Med, Reykjavik, Iceland;deCODE Genet, Reykjavik, Iceland.
    Steinhagen-Thiessen, Elisabeth
    Harvard Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Boston, MA USA.
    Stolk, Lisette
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands.
    Streeten, Elizabeth A.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA;Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
    Styrkarsdottir, Unnur
    deCODE Genet, Reykjavik, Iceland.
    Swart, Karin M. A.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands;Vrije Univ Amsterdam Med Ctr, EMGO Inst, Amsterdam, Netherlands.
    Thompson, Patricia
    Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA;SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA.
    Thomson, Cynthia A.
    Thorleifsson, Gudmar
    deCODE Genet, Reykjavik, Iceland.
    Thorsteinsdottir, Unnur
    Univ Iceland, Fac Med, Reykjavik, Iceland;deCODE Genet, Reykjavik, Iceland.
    Tikkanen, Emmi
    Natl Inst Hlth & Welfare, Helsinki, Finland;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
    Tranah, Gregory J.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
    Uitterlinden, Andre G.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Ctr Med Syst Biol & Netherlands Consortium H, Leiden, Netherlands.
    van Schoor, Natasja M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands;Vrije Univ Amsterdam Med Ctr, EMGO Inst, Amsterdam, Netherlands.
    Vandenput, Liesbeth
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Vollenweider, Peter
    Lausanne Univ Hosp, Dept Med Internal Med, Lausanne, Switzerland;Fac Biol & Med, Lausanne, Switzerland.
    Volzke, Henry
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Wactawski-Wende, Jean
    Univ Buffalo SUNY, Dept Epidemiol & Environm Hlth, Buffalo, NY USA.
    Walker, Mark
    Newcastle Univ, Med Sch, Inst Cellular Med Diabetes, Framlington Pl, Newcastle Upon Tyne, Tyne & Wear, England.
    Wareham, Nicholas J.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge, England.
    Waterworth, Dawn
    GlaxoSmithKline, Genet, King Of Prussia, PA USA.
    Weedon, Michael N.
    Univ Exeter, Med Sch, Royal Devon & Exeter Hosp, Genet Complex Traits, Exeter, Devon, England.
    Wichmann, H-Erich
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Neuherberg, Germany;Tech Univ, Inst Med Stat & Epidemiol, Munich, Germany.
    Widen, Elisabeth
    Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
    Williams, Frances M. K.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London, England.
    Wilson, James F.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Teviot Pl, Edinburgh, Midlothian, Scotland.
    Wright, Nicole C.
    Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
    Yerges-Armstrong, Laura M.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA;GlaxoSmithKline, Genet, King Of Prussia, PA USA.
    Yu, Lei
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
    Zhang, Weihua
    Ealing Hosp NHS Trust, Cardiol, London, England;Imperial Coll Healthcare NHS Trust, London, England.
    Zhao, Jing Hua
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge, England.
    Zhou, Yanhua
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Nielson, Carrie M.
    Oregon Hlth & Sci Univ, Portland, OR USA.
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA.
    Demissie, Serkalem
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Kiel, Douglas P.
    Hebrew Senior Life Inst Aging Res, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Disentangling the genetics of lean mass2019In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 109, no 2, p. 276-287Article in journal (Refereed)
    Abstract [en]

    Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age(2), and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LMwere termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

  • 25. Kitson, Alison
    et al.
    Carr, Devin
    Conroy, Tiffany
    Feo, Rebecca
    Grønkjær, Mette
    Huisman-de Waal, Getty
    Jackson, Debra
    Jeffs, Lianne
    Merkley, Jane
    Muntlin Athlin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Parr, Jennifer
    Richards, David A
    Sørensen, Erik Elgaard
    Wengström, Yvonne
    Speaking Up for Fundamental Care: the ILC Aalborg Statement2019In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, no 12, article id e033077Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The International Learning Collaborative (ILC) is an organisation dedicated to understanding why fundamental care, the care required by all patients regardless of clinical condition, fails to be provided in healthcare systems globally. At its 11th annual meeting in 2019, nursing leaders from 11 countries, together with patient representatives, confirmed that patients' fundamental care needs are still being ignored and nurses are still afraid to 'speak up' when these care failures occur. While the ILC's efforts over the past decade have led to increased recognition of the importance of fundamental care, it is not enough. To generate practical, sustainable solutions, we need to substantially rethink fundamental care and its contribution to patient outcomes and experiences, staff well-being, safety and quality, and the economic viability of healthcare systems.

    KEY ARGUMENTS: We present five propositions for radically transforming fundamental care delivery:Value: fundamental care must be foundational to all caring activities, systems and institutionsTalk: fundamental care must be explicitly articulated in all caring activities, systems and institutions.Do: fundamental care must be explicitly actioned and evaluated in all caring activities, systems and institutions.Own: fundamental care must be owned by each individual who delivers care, works in a system that is responsible for care or works in an institution whose mission is to deliver care.

    RESEARCH: fundamental care must undergo systematic and high-quality investigations to generate the evidence needed to inform care practices and shape health systems and education curricula.

    CONCLUSION: For radical transformation within health systems globally, we must move beyond nursing and ensure all members of the healthcare team-educators, students, consumers, clinicians, leaders, researchers, policy-makers and politicians-value, talk, do, own and research fundamental care. It is only through coordinated, collaborative effort that we will, and must, achieve real change.

  • 26.
    Larsson, D.
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden.
    Farahmand, Bahman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.