期刊
PLOS MEDICINE
卷 10, 期 6, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pmed.1001474
关键词
-
资金
- ENGAGE (European Network for Genetic and Genomic Epidemiology) Consortium
- European Community [201413, CEED3 223211, LSHM-CT-2006-037593]
- Academy of Finland [104781, 120315, 129418, 139635, 141054]
- Center of Excellence in Complex Disease Genetics [213506, 129680]
- SALVE research program [129418, 129494]
- Australian National Health and Medical Research Council [241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498]
- Australian Research Council [A7960034, A79906588, A79801419, DP0770096, DP0212016, DP0343921]
- Avera Institute, Sioux Falls, South Dakota (USA)
- Biobanking and Biomolecular Resources Research Infrastructure (BBMRI -NL) [184.021.007]
- Biotechnology and Biological Sciences Research Council (BBSRC)
- British Heart Foundation
- Center for Medical Systems Biology (CSMB, NWO Genomics)
- Center of Excellence in Genomics (EXCEGEN)
- Chronic Disease Research Foundation (CDRF)
- City of Malmo
- Crafoord Foundation
- Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre
- Development Fund of University of Tartu (SP1GVARENG)
- Diabetes Programme at the Lund University
- Erasmus MC
- Erasmus University Rotterdam
- Estonian Government [SF0180142s08]
- Estonian Research Roadmap through Estonian Ministry of Education and Research [3.2.0304.11-0312]
- Estonian Science Foundation [EstSF ETF9353]
- EU [QLG2-CT-2002-01254, EU/QLRT-2001-01254]
- EUR Fellowship
- European Commission (EURO-BLCS) [QLG1-CT-2000-0164, FP6 STRP 018947, LSHG-CT-2006019473]
- European Foundation for the Study of Diabetes (EFSD)
- European Science Council (ERC) [230374]
- European Science Foundation (ESF) [EU/QLRT-2001-01254]
- European Union [EU/WLRT-2001-01254]
- EUROSPAN (European Special Populations Research Network)
- Faculty of Medicine, Lund University
- Fellowship Schemes NBIC/BioAssist/RK [2008.024]
- Finnish Diabetes Research Society
- Finnish Foundation for Cardiovascular Research
- Folkhalsan Research Foundation
- Foundation for Life and Health in Finland
- Foundation for the US National Institutes of Health
- French Institute of Health and Medical Research [U258]
- Genetic Association Information Network (GAIN)
- German Federal Ministry of Education and Research (BMBF)
- German National Genome Research Network (NGFNPlus) [01GS0834]
- German Research Center for Environmental Health
- Guide Dogs for the blind Association(GDBA)
- Health Administration of Regione Lombardia [9783/1986, 41795/1993, 31737/1997, 17155/2004]
- Health Informatics Centre
- Helmholtz Zentrum Munchen
- High Performance Computing Center of University of Tartu
- International Agency for Research on Cancer
- Internationale Stichting Alzheimer Onderzoek (ISAO)
- Jakobstad Hospital
- K Medical Research Council
- Knut and Alice Wallenberg Foundation
- LMUinnovativ
- Manpei Suzuki Diabetes Foundation
- Medical Research Council, UK [G0500539, G0600705]
- Medical Society of Finland
- Ministry of Education, Culture and Science, The Netherlands
- Ministry of Health Welfare and Sports, The Netherlands
- Munich Center of Health Sciences (MC Health)
- Municipality of Rotterdam
- National Cancer Institute [N01-RC-37004]
- My Europia Research Training Network
- National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit
- National Health and Medical Research Council (NHMRC)
- National Eye Institute via an NIH/CIDR genotyping project [R01EY018246-01-1]
- National Institute of Aging (NIA)
- Netherlands Brain Foundation (HersenStichting Nederland)
- Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]
- Netherlands Genomics Initiative (NGI)
- Netherlands Heart Foundation
- Netherlands Organization for Health Research and Development (ZonMw) [10-000-1002, 904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717]
- Netherlands Organization for Scientific Research (NWO) [175.010.2005.011, 911-03-012, 918-76-619, 916.12.154, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192]
- Netherlands Scientific Organization [904-61-090, 904-61-193, 480-04-004, 400-05717, I 480-05-003]
- Neuroscience Campus Amsterdam (NCA)
- NHLBI [5R01HL087679-02]
- Novo Nordisk Foundation
- Narpes Research Foundation
- Ollqvist Foundation
- Pfizer Global Research Awards for Nicotine Dependence (GRAND)
- Pfizer Pharmaceuticals
- Pahlsson Foundation
- Region Skane
- Research Institute for Diseases in the Elderly [014-93-015, RIDE, RIDE2]
- Royal Swedish Academy of Sciences
- Rutgers University Cell and DNA Repository [NIMH U24 MH068457-06]
- Seventh Framework Programme ENGAGE project [HEALTH-F4-2007-201413]
- Signe and Ane Gyllenberg Foundation
- Sigrid Juselius Foundation
- STAMPEED program [1RL1MH083268-01]
- Swedish Cancer Society
- Swedish Cultural Foundation in Finland
- Swedish Diabetes Foundation
- Swedish Diabetes Research Society
- Swedish Foundation for Strategic Research (SSF) [ICA08-0047]
- Swedish Heart and Lung Foundation
- Swedish Medical Research Council
- Swedish Ministry for Higher Education
- Swedish Research Council for Medicine and Health [349-2008-6589, Exodiab 2009-1039, M-2005-1112, 2009-2298]
- Swedish Research Council for Infrastructures
- Swedish Society of Medicine
- US NIH [AA07535, AA10248, AA11998, AA13320, AA13321, AA13326, AA14041, AA15416, AA17688, DA12854, MH66206, R01D0042157-01A, AG028555, AG08724, AG04563, AG10175, AG08861, R01HL089650-02, DK U01-066134, 5R01MH63706: 02, RO1 MH059160, 1RC2MH089951-01]
- University Hospital Oulu
- University of Dundee
- University of Ulm
- Uppsala University
- Uppsala University Hospital
- US National Heart, Lung and Blood Institute
- US Public Health Service
- Vasa and Narpes Health centers
- Wellcome Trust
- Wellcome Trust Sanger Institute
- VU University's Institute for Health and Care Research (EMGO+)
- Swedish Foundation for Strategic Research (SSF) [ICA08-0047] Funding Source: Swedish Foundation for Strategic Research (SSF)
- Academy of Finland (AKA) [129418] Funding Source: Academy of Finland (AKA)
- British Heart Foundation [PG/09/023/26806] Funding Source: researchfish
- Economic and Social Research Council [ES/G007438/1] Funding Source: researchfish
- Medical Research Council [G0801056, G0801056B, G0600705, G0902313, MC_UU_12013/1] Funding Source: researchfish
- National Institute for Health Research [SRF/01/010, NF-SI-0611-10099] Funding Source: researchfish
- Novo Nordisk Fonden [NNF12OC1016467] Funding Source: researchfish
- ESRC [ES/G007438/1] Funding Source: UKRI
- MRC [G0902313, MC_UU_12013/1, G0801056, G0600705] Funding Source: UKRI
Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据