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

• Published in: British journal of psychiatry 2017-08, Vol.211 (2), p.70-76
• Main Authors: Rivera, Margarita, Locke, Adam E., Corre, Tanguy, Czamara, Darina, Wolf, Christiane, Ching-Lopez, Ana, Milaneschi, Yuri, Kloiber, Stefan, Cohen-Woods, Sara, Rucker, James, 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, Müller-Myhsok, Bertram, Owen, Michael J., Penninx, Brenda W. J. H., 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, McGuffin, Peter
• Format: Article
• Language: English
• Subjects: Alleles; Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics; Analysis; Antidepressants; Body Mass Index; Case-Control Studies; Comorbidity; Depressive Disorder, Major - epidemiology; Depressive Disorder, Major - genetics; Discovery; Fto gene; Genetic Predisposition to Disease - genetics; Humans; Mental depression; Meta-analysis; Obesity; Obesity - epidemiology; Obesity - genetics; Polymorphism, Genetic - genetics; Psychiatry; Public health; Random effects; Regression analysis; Review; Review Articles; Systematic review
• ISSN: 0007-1250; 1472-1465
• DOI: 10.1192/bjp.bp.116.183475

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 gene, suggesting its implication in the association between depression and obesity. To confirm these findings by investigating the polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis. 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. In the replication cohorts, we observed a significant interaction between , BMI and depression with fixed effects meta-analysis (β = 0.12, = 2.7 × 10 ) and with the Han/Eskin random effects method ( = 1.4 × 10 ) but not with traditional random effects (β = 0.1, = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, = 0.027) being highly significant based on the Han/Eskin model ( = 6.9 × 10 ). 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 This meta-analysis provides additional support for a significant interaction between , depression and BMI, indicating that depression increases the effect of on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.