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Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults

Zimmermann, E and Ängquist, LH and Mirza, SS and Zhao, JH and Chasman, DI and Fischer, K and Qi, Q and Smith, AV and Thinggaard, M and Jarczok, MN and Nalls, MA and Trompet, S and Timpson, NJ and Schmidt, B and Jackson, AU and Lyytikäinen, LP and Verweij, N and Mueller-Nurasyid, M and Vikström, M and Marques-Vidal, P and Wong, A and Meidtner, K and Middelberg, RP and Strawbridge, RJ and Christiansen, L and Kyvik, KO and Hamsten, A and Jääskeläinen, T and Tjønneland, A and Eriksson, JG and Whitfield, JB and Boeing, H and Hardy, R and Vollenweider, P and Leander, K and Peters, A and van der Harst, P and Kumari, M and Lehtimäki, T and Meirhaeghe, A and Tuomilehto, J and Jöckel, KH and Ben-Shlomo, Y and Sattar, N and Baumeister, SE and Davey Smith, G and Casas, JP and Houston, DK and März, W and Christensen, K and Gudnason, V and Hu, FB and Metspalu, A and Ridker, PM and Wareham, NJ and Loos, RJF and Tiemeier, H and Sonestedt, E and Sørensen, TIA and Orho-Melander, M and Zillikens, C and A. Ikram, and Hofman, A and Luan, J and Khaw, KT and Rose, LM and Läll, K and Mägi, R and Qi, L and Sun, Q and T.B. Harris, and Launer, LJ and Eiriksdottir, G and Kleber, ME and Delgado, G and Liu, Y and Garcia, M and Teumer, A and Grabe, H and Homuth, G and J.W. Jukema, and Ford, I and M. de Craen, AJ and Gallacher, J and Yarnell, J and Mahabadi, AA and Nöthen, MM and Erbel, R and Stringham, HM and Boehnke, M and Amouyel, P and J. Ferrières, and Arveiler, D and M. Kähönen, and Nikus, K and T. Nieminen, and Sanchez, A and Kivimaki, M and J.V. van Vliet-Ostaptchouk, and Hampel, R (2015) 'Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.' Obesity Reviews, 16 (4). 327 - 340. ISSN 1467-7881

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Abstract

© 2015 World Obesity. 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; 0.32kgm -2 ; 95% CI 0.28-0.32, P<1×10 -32 ), WC (n=152,631; 0.76cm; 0.68-0.84, P<1×10 -32 ) and FMI (n=48,192; 0.17kgm -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.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Jim Jamieson
Date Deposited: 15 May 2015 14:07
Last Modified: 01 May 2019 00:15
URI: http://repository.essex.ac.uk/id/eprint/13696

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