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Fall, T.* ; Hägg, S.* ; Mägi, R.* ; Ploner, A.* ; Fischer, K.* ; Horikoshi, M.* ; Sarin, A.P.* ; Thorleifsson, G.* ; Ladenvall, C.* ; Kals, M.* ; Kuningas, M.* ; Draisma, H.H.* ; Ried, J.S. ; van Zuydam, N.* ; Huikari, V.* ; Mangino, M.* ; Sonestedt, E.* ; Benyamin, B.* ; Nelson, C.P.* ; Rivera, N.V.* ; Kristiansson, K.* ; Shen, H.Y.* ; Havulinna, A.S.* ; Dehghan, A.* ; Donnelly, L.A.* ; Kaakinen, M.* ; Nuotio, M.L.* ; Robertson, N.* ; de Bruijn, R.F.* ; Ikram, M.A.* ; Amin, N.* ; Balmforth, A.J.* ; Braund, P.S.* ; Doney, A.S.* ; Döring, A. ; Elliott, P.* ; Esko, T.* ; Franco, O.H.* ; Gretarsdottir, S.* ; Hartikainen, A.L.* ; Heikkilä, K.* ; Herzig, K.H.* ; Holm, H.* ; Hottenga, J.J.* ; Hyppönen, E.* ; Illig, T. ; Isaacs, A.* ; Isomaa, B.* ; Karssen, L.C.* ; Kettunen, J.* ; Koenig, W.* ; Kuulasmaa, K.* ; Laatikainen, T.* ; Laitinen, J.* ; Lindgren, C.* ; Lyssenko, V.* ; Läärä, E.* ; Rayner, N.W.* ; Männistö, S.* ; Pouta, A.* ; Rathmann, W.* ; Rivadeneira, F.* ; Ruokonen, A.* ; Savolainen, M.J.* ; Sijbrands, E.J.* ; Small, K.S.* ; Smit, J.H.* ; Steinthorsdottir, V.* ; Syvanen, A.C.* ; Taanila, A.* ; Tobin, M.D.* ; Uitterlinden, A.G.* ; Willems, S.M.* ; Willemsen, G.* ; Witteman, J.* ; Perola, M.* ; Evans, A.* ; Ferrieres, J.* ; Virtamo, J.* ; Kee, F.* ; Tregouet, D.A.* ; Arveiler, D.* ; Amouyel, P.* ; Ferrario, M.M.* ; Brambilla, P.* ; Hall, A.S.* ; Heath, A.C.* ; Madden, P.A.* ; Martin, N.G.* ; Montgomery, G.W.* ; Whitfield, J.B.* ; Jula, A.* ; Knekt, P.* ; Oostra, B.* ; van Duijn, C.M.* ; Penninx, B.W.* ; Davey Smith, G.* ; Kaprio, J.* ; Samani, N.J.* ; Gieger, C. ; Peters, A. ; Wichmann, H.-E. ; Boomsma, D.I.* ; de Geus, E.J.* ; Tuomi, T.* ; Power, C.* ; Hammond, C.J.* ; Spector, T.D.* ; Lind, L.* ; Orho-Melander, M.* ; Palmer, C.N.* ; Morris, A.D.* ; Groop, L.* ; Jarvelin, M.R.* ; Salomaa, V.* ; Vartiainen, E.* ; Hofman, A.* ; Ripatti, S.* ; Metspalu, A.* ; Thorsteinsdottir, U.* ; Stefansson, K.* ; Pedersen, N.L.* ; McCarthy, M.I.* ; Ingelsson, E.* ; Prokopenko, I.* ; ENGAGE Consortium (*)

The role of adiposity in cardiometabolic traits: A mendelian randomization analysis.

PLoS Med. 10:e1001474 (2013)
Publ. Version/Full Text Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Body-mass Index ; Impaired Glucose-tolerance ; Genome-wide Association ; Heart-failure ; Life-style ; Fto Gene ; Diabetes Prevention ; Obesity ; Risk ; Disease
ISSN (print) / ISBN 1549-1277
e-ISSN 1549-1676
Journal PLoS Medicine
Quellenangaben Volume: 10, Issue: 6, Pages: , Article Number: e1001474 Supplement: ,
Publisher Public Library of Science (PLoS)
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Research Unit Molecular Epidemiology (AME)
Institute of Epidemiology (EPI)
Institute of Epidemiology II (EPI2)