The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis

Van, N. R.; van Zuydam, Natalie R.; Van, C. M.; Fall, T .; Hägg, Sara; Sarin, Antti-Pekka; Mägi, Reedik; Hagg, Sara; de Bruijn, Renée F. A. G.; Draisma, Harmen H. M.; Ploner, Alexander; Maegi, Reedik; Ried, Janina S.; Huikari, Ville; Fischer, Krista; Mangino, Massimo; Sonestedt, Emily; H. H. M.,; Benyamin, Beben; Horikoshi, Momoko; Nelson, Christopher P.; Rivera, Natalia V.; Kristiansson, Kati; Shen, Huei-Yi; Havulinna, Aki S.; Dehghan, Abbas; Donnelly, Louise A.; Thorleifsson, Gudmar; Kaakinen, Marika; Nuotio, Marja-Liisa; Robertson, Neil; Ladenvall, Claes; Kals, Mart; Ikram, Arfan M.; Bruijn, Renée F. A. G.; Amin, Najaf; Ikram, M. Arfan; Balmforth, Anthony J.; Tobin, Martin D.; R. F. A.,; Braund, Peter S.; Kuningas, Maris; Uitterlinden, Andre G.; Doney, Alexander S. F.; Willems, Sara M.; Ikram, M. A.; Döring, Angela; Willemsen, Gonneke; Elliott, Paul; Witteman, Jacqueline; Esko, Tõnu; Franco, Oscar H.; Virtamo, Jarmo; Doering, Angela; Gretarsdottir, Solveig; Tregouet, David-Alexandre; Hartikainen, Anna-Liisa; Heikkilä, Kauko; A. S. F.,; Herzig, Karl-Heinz; Holm, Hilma; Hottenga, Jouke Jan; Hyppönen, Elina; Whitfield, John B.; Illig, Thomas; Isaacs, Aaron; van Duijn, Cornelia M.; Isomaa, Bo; Karssen, Lennart C.; Kettunen, Johannes; Koenig, Wolfgang; Kuulasmaa, Kari; Wichmann, H.-Erich; de Geus, Eco J. C.; Laatikainen, Tiina; Laitinen, Jaana; Tuomi, TiinaMaija M.; Lindgren, Cecilia; Lyssenko, Valeriya; Läärä, Esa; Rayner, Nigel W.; Männistö, Satu; Vartiainen, Erkki; Pouta, Anneli; Rathmann, Wolfgang; Rivadeneira, Fernando; Thorsteinsdottir, Unnur; Laara, Esa; Ruokonen, Aimo; Savolainen, Markku J.; Mannisto, Satu; Sijbrands, Eric J. G.; Small, Kerrin S.; Smit, Jan H.; Steinthorsdottir, Valgerdur; Ap, Sarin; Syvänen, Ann-Christine; Taanila, Anja; E. J. G.,; Perola, Markus; Evans, Alun; Ferrières, Jean; Kee, Frank; Arveiler, Dominique; Amouyel, Philippe; P. A. F.,; Ferrario, Marco M.; Brambilla, Paolo; Hall, Alistair S.; Heath, Andrew C.; Madden, Pamela A. F.; Martin, Nicholas G.; Montgomery, Grant W.; B. W. J.,; Jula, Antti; Knekt, Paul; Oostra, Ben; Smith, George Davey; Penninx, Brenda W. J. H.; Erich Wichmann, H.; Davey Smith, George; Kaprio, Jaakko; Samani, Nilesh J.; Gieger, Christian; E. J. C.,; Peters, Annette; Boomsma, Dorret I.; Alexander, C. N.; Power, Chris; Hammond, Christopher J.; Spector, Tim D.; Hh, Draisma; Lind, Lars; Orho-Melander, Marju; Jarvelin, Marjo-Riitta; Palmer, Colin Neil Alexander; Morris, Andrew D.; Groop, Leif; Järvelin, Marjo-Riitta; Salomaa, Veikko; Hofman, Albert; Ripatti, Samuli; Js, Ried; Metspalu, Andres; Genetic, European Network; For, E. N.; Stefansson, Kari; Pedersen, Nancy L.; McCarthy, Mark I.; Consortium, European Network for Genetic and Genomic Epidemiology (ENGAGE); Ingelsson, Erik; E. (Engage), G.; Prokopenko, Inga; Engage, Consortium

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Public Library of Science, PLoS Medicine, 6(10), p. e1001474, 2013

DOI: 10.1371/journal.pmed.1001474

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The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis

Journal article published in 2013 by N. R. Van, Natalie R. van Zuydam, C. M. Van, T . Fall, Sara Hägg, Antti-Pekka Sarin, Reedik Mägi, Sara Hagg, Renée F. A. G. de Bruijn, Harmen H. M. Draisma, Alexander Ploner, Reedik Maegi, Janina S. Ried, Ville Huikari, Krista Fischer and other authors.

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Abstract

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

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The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis

Abstract