Interaction between the <i>FTO</i> gene, body mass index and depression: meta-analysis of 13701 individualst

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Rivera, Margarita, Locke, Adam E, Corre, Tanguy, Czamara, Darina, Wolf, Christiane, Ching-Lopez, Ana, Milaneschi, Yuri, Kloiber, Stefan, Cohen-Woods, Sara, Rucker, James et al (show 28 more authors) , Aitchison, Katherine J, Bergmann, Sven, Boomsma, Dorret I, Craddock, Nick, Gill, Michael, Holsboer, Florian, Hottenga, Jouke-Jan, Korszun, Ania, Kutalik, Zoltan, Lucae, Susanne, Maier, Wolfgang, Mors, Ole, Mueller-Myhsok, Bertram ORCID: 0000-0002-0719-101X, Owen, Michael J, Penninx, Brenda WJH, Preisig, Martin, Rice, John, Rietschel, Marcella, Tozzi, Federica, Uher, Rudolf, Vollenweider, Peter, Waeber, Gerard, Willemsen, Gonneke, Craig, Ian W, Farmer, Anne E, Lewis, Cathryn M, Breen, Gerome and McGuffin, Peter (2017) Interaction between the <i>FTO</i> gene, body mass index and depression: meta-analysis of 13701 individualst. BRITISH JOURNAL OF PSYCHIATRY, 211 (2). pp. 70-76.

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Abstract

<b>Background</b>Depression 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 <i>FTO</i> gene, suggesting its implication in the association between depression and obesity.<b>Aims</b>To confirm these findings by investigating the <i>FTO</i> polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.<b>Method</b>The 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.<b>Results</b>In the replication cohorts, we observed a significant interaction between <i>FTO</i>, BMI and depression with fixed effects meta-analysis (β = 0.12, <i>P</i> = 2.7 × 10^-4) and with the Han/Eskin random effects method (<i>P</i> = 1.4 × 10^-7) but not with traditional random effects (β = 0.1, <i>P</i> = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, <i>P</i> = 0.027) being highly significant based on the Han/Eskin model (<i>P</i> = 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 <i>FTO</i><b>Conclusions</b>This meta-analysis provides additional support for a significant interaction between <i>FTO</i>, depression and BMI, indicating that depression increases the effect of <i>FTO</i> on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.

Item Type:	Article
Uncontrolled Keywords:	Humans, Obesity, Genetic Predisposition to Disease, Body Mass Index, Case-Control Studies, Depressive Disorder, Major, Comorbidity, Polymorphism, Genetic, Alleles, Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Depositing User:	Symplectic Admin
Date Deposited:	02 Aug 2017 08:01
Last Modified:	18 Oct 2023 09:49
DOI:	10.1192/bjp.bp.116.183475
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3008769