Is the adiposity‐associated FTO gene variant related to all‐cause mortality independent of adiposity? Meta‐analysis of data from 169,551 C aucasian adults
Year: 2015
Type: review
Abstract: Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.
Source: Obesity Reviews
DOI: 10.1111/obr.12263
Authors: E. Zimmermann, L. H. Ängquist, S. S. Mirza, J. H. Zhao, D. I. Chasman, K. Fischer, Q. Qi, A. V. Smith, M. Thinggaard, M. N. Jarczok, M. A. Nalls, S. Trompet, N. J. Timpson, B. Schmidt, A. U. Jackson, L. P. Lyytikäinen, N. Verweij, M. Mueller‐Nurasyid, M. Vikström, P. Marques‐Vidal, A. Wong, K. Meidtner, R. P. Middelberg, R. J. Strawbridge, L. Christiansen, The FTO‐Mortality Collaborating Group, K. O. Kyvik, A. Hamsten, T. Jääskeläinen, A. Tjønneland, J. G. Eriksson, J. B. Whitfield, H. Boeing, R. Hardy, P. Vollenweider, K. Leander, A. Peters, P. van der Harst, M. Kumari, T. Lehtimäki, A. Meirhaeghe, J. Tuomilehto, K.‐H. Jöckel, Y. Ben‐Shlomo, N. Sattar, S. E. Baumeister, G. Davey Smith, J. P. Casas, D. K. Houston, W. März, K. Christensen, V. Gudnason, F. B. Hu, A. Metspalu, P. M. Ridker, N. J. Wareham, R. J. F. Loos, H. Tiemeier, E. Sonestedt, T. I. A. Sørensen
Institutions: Frederiksberg Hospital, Bispebjerg Hospital, Erasmus MC, University of Cambridge, Addenbrooke's Hospital, MRC Epidemiology Unit, Brigham and Women's Hospital, Harvard University, University of Tartu, Albert Einstein College of Medicine, University of Iceland, Icelandic Heart Association, University of Southern Denmark, Heidelberg University, Medizinische Fakultät Mannheim, National Institutes of Health, National Institute on Aging, Leiden University Medical Center, University of Bristol, MRC Integrative Epidemiology Unit, University of Duisburg-Essen, University of Michigan, Fimlab (Finland), University of Tampere, University Medical Center Groningen, University of Groningen, Helmholtz Munich, German Centre for Cardiovascular Research, Ludwig-Maximilians-Universität München, Karolinska Institutet, Centre Hospitalier Universitaire Vaudois, MRC Unit for Lifelong Health and Ageing, University College London, German Institute of Human Nutrition, QIMR Berghofer Medical Research Institute, Odense University Hospital, University of Eastern Finland, Danish Cancer Society, University of Helsinki, Helsinki University Hospital, Finnish Institute for Health and Welfare, Folkhälsans Forskningscentrum, Netherlands Heart Institute, University of Essex, Institute for Social and Economic Research, Inserm, Institut Pasteur de Lille, Université Lille Nord de France, Universität für Weiterbildung Krems, King Abdulaziz University, Hospital Universitario La Paz, Hospital La Paz Institute for Health Research, University of Glasgow, Universitätsmedizin Greifswald, London School of Hygiene & Tropical Medicine, Wake Forest University Health Sciences, Wake Forest University, Medical University of Graz, Synlab (Germany), Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, Lund University, University of Copenhagen, Novo Nordisk Foundation, Novo Nordisk Foundation Center for Basic Metabolic Research
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: National Science Foundation, John D. and Catherine T. MacArthur Foundation, Donald W. Reynolds Foundation, Amgen, Wake Forest University, Hjerteforeningen, Foundation for Cardiovascular Research, Statens Naturvidenskabelige Forskningsrad, Sundhed og Sygdom, Det Frie Forskningsråd, Wellcome Trust, Cancer Research UK, National Institute for Health and Care Research, British Heart Foundation, Department of Health and Social Care, Food Standards Agency, Stroke Association, European Commission, Health and Safety Executive, National Research Foundation, Institut National de la Santé et de la Recherche Médicale, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Danmarks Grundforskningsfond, ZonMw, Eesti Teadusfondi, Eesti Teadusagentuur, Cancerfonden, Erasmus Medisch Centrum, Suomen Kulttuurirahasto, Ministero della Salute, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Lunds Universitet, Hjärt-Lungfonden, Karolinska Institutet, Knut och Alice Wallenbergs Stiftelse, Stockholms Läns Landsting, Vetenskapsrådet, Emil Aaltosen Säätiö, Sydäntutkimussäätiö, Syddansk Universitet, Tampereen Tuberkuloosisäätiö, Tartu Ülikool, Mutuelle Générale de l'Education Nationale, Gangstedfonden, Region Skåne, Tays, Hjartavernd, Heinz Nixdorf Stiftung, Diabetesforeningen, National Institutes of Health, Medical Research Council, Economic and Social Research Council, European Regional Development Fund, Strategic Research Council, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Eye Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, U.S. National Library of Medicine, Interreg
Awards: G100949702, G1032447267, G1072871761, G1077033501, G1083180012, Women's Health Study: Continued Follow-Up, G1099494159, G1114899569, Biomarker Research Alliance for Diagnosing Heart Disease in the Ageing European Population, G119964413, G1214533002, Genetic Determinants of Visceral Adiposity, Omics for health: an integrated approach to understand and predict human disease, G1394812629, Obesity Genes, Energy Regulation in Response to Weight-Loss Diets, DYNAMICS OF HEALTH,AGING, AND BODY COMPOSITION, G151562090, G1528515809, G1717613936, G1730292437, G1732152801, G1861573265, G1896713975, G1916810480, G2070131968, Genetic Markers of CHD in Type 2 Diabetes, G2109279595, DYNAMICS OF HEALTH, AGING, AND BODY COMPOSITION, G218565478, BBMRI - Large Prospective Cohorts, G223346726, G229684361, G230712557, Biomarker for Cardiovascular Risk Assessment in Europe, European Collaborative Project on Inflamation and Vascular Wall Remodelling in Atherosclerosis, G2580106776, Biochemical Markers in the nurses' Health Study Cohort, Genome-Wide Association Study of Endometrial Cancer, G265847165, G269567959, G2750880407, G2751663742, Determinants of healthy ageing in the Whitehall II study, G2815873878, Genes and Environment Initiatives in Type 2 Diabetes, PERSISTENCE AND CHANGE IN DRINKING HABITS--PROJECT TWO, G2929324288, Identifying Genes for Type 2 Diabetes: FUSION, Gene-Environment Interactions in Glaucoma, G2973790809, Biochemical and Genetic Markers of Type 2 Diabetes Risk, G3059241284, HEALTH ABC--COORDINATING UNIT, G3207356259, G3209059653, G3219722387, G3319515530, G3383031331, G3402222819, G3482753592, G3588481721, Boston Nutrition Obesity Research Center, G3860090032, G386535962, G3875417561, G393177772, Dietary and Hormonal Determinants of Cancer in Women, Psychiatric disorders in 35 to 65 year-old residents of the city of Lausanne and their association to cardiovasular risk factors: a population based survey, Personalized diagnostics and treatment of high risk coronary artery disease patients., G4104599821, G4130499527, G4148914313, Identifying Genes for Type 2 Diabetes: FUSION, Genes and Environment Initiative in Glaucoma, G4418243127, Genetics of Coronary Artery Disease in Type 2 Diabetes, G459566519, G4722625316, G4805355505, G494123624, G496129201, G5019773026, G518464440, G5208912463, G537455924, G5412976545, Bioinformatics Strategies for Genome Wide Association Studies, G5433162186, G5446579839, G5453233289, The Pathobiology of Nephrolithiasis, Harvard Transdisciplinary Research in Energetics and Cancer Center, Epidemiology of Precursors to Type 2 Diabetes, G558986044, G5702163051, G5744414021, G581554933, G5821446538, G5869775930, The Women's Health Study: Infrastructure Support for Continued Cohort Follow-up, G588599347, G5893983254, G5897142711, G5909482378, G6008908520, G6086542015, G6091493096, NIHR Senior Investigator Award, G6354209809, G6401035755, Mentored Patient-Oriented Research in Digestive Diseases, G670738241, TRIAL OF ASPIRIN AND VITAMIN E IN WOMEN, CHANGES IN HEALTH: SOCIO-ECONOMIC STATUS AND PATHWAYS, G6957823285, G7093047072, Molecular pathological epidemiology of colorectal cancer, Prospective Studies of Diet and Cancer in Men and Women, G7253798699, G7286868595, G7373387228, G7374949320, and High resolution analysis of biological and environmental determinants of cardiovascular risk factors and cardiovascular events in older women, G7552017953, Vascular risk and functional decline in old age (renewal), G7672858748, G7710883045, Biochemical Markers in the Nurses? Health Study Cohort, G772621625, VARIATION IN THE EFFECTS OF ALCOHOL ON LIVER FUNCTION, G7752462009, A PHArmacogenomic study of Statins in the Elderly at risk for cardiovascular disease, Women's Health Study: Continued Follow-up, G7962241407, G820615960, G8267674335, G83951392, NIHR Senior Investigator Award, G8506930532, Socio-economic status and heterogeneity in aging, Socioeconomic gradient in CHD in early old age, PERSISTENCE AND CHANGE IN DRINKING HABITS--TWIN STUDY, G861947890, G870807107, SUrrogate markers for vascular Micro- and Macrovascular hard endpoints for Innovative diabetes Tools, G890705022, G9000028950, G9000029955, G9000058182, G9000190097, G9000207591, G9000258954, G9000277595, G9000282657, Identifying Genes for Type 2 Diabetes: FUSION, RISK FACTORS FOR CVD IN WOMEN, Risk Factors for Ischemic Stroke in Women, G945304896, G985071772
OpenAlex ID: W2116057749