Genetic Relationship Between Depression and Body Mass Index

Introduction Depression and obesity are highly prevalent major public health problems that frequently co-occur. Shared aetiological factors have been found between depression and obesity. The role of the fat mass and obesity associated ( FTO ) gene in body mass index (BMI) and obesity has been confirmed in many independent studies. Recently, we reported the first study implicating FTO in the association between depression and obesity. Objectives We aimed to confirm these findings by investigating the FTO rs9939609 polymorphism in a meta-analysis of 13,701 individuals. Methods The sample consists of 6,902 depressed cases and 6,799 controls from five studies (Radiant, PsyCoLaus, GSK, MARS and NESDA/NTR). Common inclusion criteria were information available on a lifetime DSM-IV diagnosis of major depressive disorder (MDD), BMI and genotype data. Linear regression models for quantitative traits assuming an additive genetic model were performed to test for association and interaction between rs9939609, BMI and depression. Fixed and random-effects meta-analyses were performed. Results Fixed-effects meta-analyses support a significant association between rs9939609 polymorphism and BMI (whole-sample: s=0.07, p=1.29×10 -12 , depressive-cases: s=0.12, p=6.92×10 -12 ). No association was found in controls (s=0.02, p=0.15). Meta-analyses further support a significant interaction between FTO , BMI and depression (fixed-effects: s=0.13, p=3.087×10 -7 ; random-effects: s=0.12, p=0.027), wherein depressed carriers of the risk allele have an additional increase of 2.2% in BMI. Conclusions This meta-analysis demonstrates a significant interaction between FTO , depression and BMI, indicating that depression increases the effect of FTO on BMI. Depression-related alterations in key biological processes may interact with the rs9939609 FTO risk allele to increase obesity risk.