Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals

Margarita Rivera, Adam E Locke, Tanguy Corre, Darina Czamara, Christiane Wolf, Ana Ching-Lopez, Yuri Milaneschi, Stefan Kloiber, Sara Cohen-Woods, James Rucker, Katherine J Aitchison, Sven Bergmann, Dorret I Boomsma, Nick Craddock, Michael Gill, Florian Holsboer, Jouke-Jan Hottenga, Ania Korszun, Zoltan Kutalik, Susanne LucaeWolfgang Maier, Ole Mors, Bertram Müller-Myhsok, Michael J Owen, Brenda W J H Penninx, Martin Preisig, John P Rice, Marcella Rietschel, Federica Tozzi, Rudolf Uher, Peter Vollenweider, Gerard Waeber, Gonneke Willemsen, Ian W Craig, Anne E Farmer, Cathryn M Lewis, Gerome Breen, Peter McGuffin

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Abstract

BackgroundDepression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.AimsTo confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.MethodThe sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.ResultsIn the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β = 0.12, P = 2.7 × l0(-4)) and with the Han/Eskin random effects method (P = 1.4 × 10(-7)) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10(-8)). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTOConclusionsThis meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.

Original languageEnglish
Pages (from-to)70-76
Number of pages7
JournalBritish Journal of Psychiatry
Volume211
Issue number2
DOIs
Publication statusPublished - 1 Aug 2017

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Rivera, M., Locke, A. E., Corre, T., Czamara, D., Wolf, C., Ching-Lopez, A., ... McGuffin, P. (2017). Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals. British Journal of Psychiatry, 211(2), 70-76. https://doi.org/10.1192/bjp.bp.116.183475