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The role of adiposity in cardiometabolic traits: a mendelian randomization analysis

Title:	The role of adiposity in cardiometabolic traits: a mendelian randomization analysis
Authors:	Fall, T; Hägg, S; Mägi, R; Ploner, A; Fischer, K; Horikoshi, M; Sarin, AP; Thorleifsson, G; Ladenvall, C; Kals, M; Kuningas, M; Draisma, HH; Ried, JS; van, Zuydam; NR; Huikari, V; Mangino, M; Sonestedt, E; Benyamin, B; Nelson, CP; Rivera, NV; Kristiansson, K; Shen, HY; Havulinna, AS; Dehghan, A; Donnelly, LA; Kaakinen, M; Nuotio, ML; Robertson, N; de Bruijn, RF; Ikram, MA; Amin, N; Balmforth, AJ; Braund, PS; Doney, AS; Döring, A; Elliott, P; Esko, T; Franco, OH; Gretarsdottir, S; Hartikainen, AL; Heikkilä, K; Herzig, KH; Holm, H; Hottenga, JJ; Hyppönen, E; Illig, T; Isaacs, A; Isomaa, B; Karssen, LC; Kettunen, J; Koenig, W; Kuulasmaa, K; Laatikainen, T; Laitinen, J; Lindgren, C; Lyssenko, V; Läärä, E; Rayner, NW; Männistö, S; Pouta, A; Rathmann, W; Rivadeneira, F; Ruokonen, A; Savolainen, MJ; Sijbrands, EJ; Small, KS; Smit, JH; Steinthorsdottir, V; Syvänen, AC; Taanila, A; Tobin, MD; Uitterlinden, AG; Willems, SM; Willemsen, G; Witteman, J; Perola, M; Evans, A; Ferrières, J; Virtamo, J; Kee, F; Tregouet, DA; Arveiler, D; Amouyel, P; Ferrario, MM; BRAMBILLA, PAOLO; Hall, AS; Heath, AC; Madden, PA; Martin, NG; Montgomery, GW; Whitfield, JB; Jula, A; Knekt, P; Oostra, B; van Duijn, CM; Penninx, BW; Davey Smith, G; Kaprio, J; Samani, NJ; Gieger, C; Peters, A; Wichmann, HE; Boomsma, DI; de Geus, EJ; Tuomi, T; Power, C; Hammond, CJ; Spector, TD; Lind, L; Orho Melander, M; Palmer, CN; Morris, AD; Groop, L; Järvelin, MR; Salomaa, V; Vartiainen, E; Hofman, A; Ripatti, S; Metspalu, A; Thorsteinsdottir, U; Stefansson, K; Pedersen, NL; McCarthy, MI; Ingelsson, E; Prokopenko, I.
Contributors:	Fall, T; Hägg, S; Mägi, R; Ploner, A; Fischer, K; Horikoshi, M; Sarin, A; Thorleifsson, G; Ladenvall, C; Kals, M; Kuningas, M; Draisma, H; Ried, J; Van, Z; Nr; Huikari, V; Mangino, M; Sonestedt, E; Benyamin, B; Nelson, C; Rivera, N; Kristiansson, K; Shen, H; Havulinna, A; Dehghan, A; Donnelly, L; Kaakinen, M; Nuotio, M; Robertson, N; de Bruijn, R; Ikram, M; Amin, N; Balmforth, A; Braund, P; Doney, A; Döring, A; Elliott, P; Esko, T; Franco, O; Gretarsdottir, S; Hartikainen, A; Heikkilä, K; Herzig, K; Holm, H; Hottenga, J; Hyppönen, E; Illig, T; Isaacs, A; Isomaa, B; Karssen, L; Kettunen, J; Koenig, W; Kuulasmaa, K; Laatikainen, T; Laitinen, J; Lindgren, C; Lyssenko, V; Läärä, E; Rayner, N; Männistö, S; Pouta, A; Rathmann, W; Rivadeneira, F; Ruokonen, A; Savolainen, M; Sijbrands, E; Small, K; Smit, J; Steinthorsdottir, V; Syvänen, A; Taanila, A; Tobin, M; Uitterlinden, A; Willems, S; Willemsen, G; Witteman, J; Perola, M; Evans, A; Ferrières, J; Virtamo, J; Kee, F; Tregouet, D; Arveiler, D; Amouyel, P; Ferrario, M; Brambilla, P; Hall, A; Heath, A; Madden, P; Martin, N; Montgomery, G; Whitfield, J; Jula, A; Knekt, P; Oostra, B; van Duijn, C; Penninx, B; Davey Smith, G; Kaprio, J; Samani, N
Publisher Information:	Public Library of Science; US
Publication Year:	2013
Collection:	Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive)
Subject Terms:	adiposity; rs9939609; BMI; heart failure; Settore BIOS-09/A - Biochimica clinica e biologia molecolare clinica
Description:	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
Document Type:	article in journal/newspaper
File Description:	ELETTRONICO
Language:	English
Relation:	info:eu-repo/semantics/altIdentifier/pmid/23824655; info:eu-repo/semantics/altIdentifier/wos/WOS:000321034800017; volume:10; issue:6; journal:PLOS MEDICINE; https://hdl.handle.net/10281/45706
DOI:	10.1371/journal.pmed.1001474
Availability:	https://hdl.handle.net/10281/45706; https://doi.org/10.1371/journal.pmed.1001474
Rights:	info:eu-repo/semantics/openAccess ; license:Creative Commons ; license uri:http://creativecommons.org/licenses/by/4.0/
Accession Number:	edsbas.49BC21F3
Database:	BASE