Depressive disorder moderates the effect of the FTO gene on body mass index
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AuteurRivera Sánchez, Margarita
DepressionFTO geneObesityBody mass index (BMI)
Published version: Rivera, M., Cohen-Woods, S., Kapur, K. et al. Depressive disorder moderates the effect of the FTO gene on body mass index. Mol Psychiatry 17, 604–611 (2012). [https://doi.org/10.1038/mp.2011.45]
PatrocinadorMedical Research Council UK (MRC); GlaxoSmithKline G0701420; European Commission Joint Research Centre LSHB-CT-2003-503428; European Community (EC); National Institute for Health Research (NIHR); Wellcome Trust; Swiss National Science Foundation (SNSF) 3200B0-105993 3200B0-118308 33CSC0122661 3100AO-116323/1; GiorgiCavaglieri Foundation; Swiss Institute of Bioinformatics; European Framework Project; Medical Research Council UK (MRC) G0801418B G0701003 G0701420 G9817803B
There is evidence that obesity related disorders are increased among people with depression. Variation in the FTO (fat mass and obesity associated) gene has been shown to contribute to common forms of human obesity. This study aimed to investigate the genetic influence of polymorphisms in FTO in relation to Body Mass Index (BMI) in two independent samples of major depressive disorder (MDD) cases and controls. We analysed 88 polymorphisms in the FTO gene in a clinically ascertained sample of 2442 MDD cases and 809 controls (Radiant Study). Eight of the top 10 SNPs showing the strongest associations with BMI were followed-up in a population-based cohort (PsyCoLaus Study) consisting of 1292 depression cases and 1690 controls. Linear regression analyses of the FTO variants and BMI yielded 10 SNPs significantly associated with increased BMI in the depressive group but not the control group in the Radiant sample. The same pattern was found in the PsyCoLaus sample. We found a significant interaction between genotype and affected status in relation to BMI for 7 SNPs in Radiant (p<0.0057), with PsyCoLaus giving supportive evidence for 5 SNPs (pvalues between 0.03-0.06) which increased in significance when the data were combined in a meta-analysis. This is the first study investigating FTO and BMI within the context of MDD, and the results indicate that having a history of depression moderates the effect of FTO on BMI. This finding suggests that FTO is involved in the mechanism underlying the association between mood disorders and obesity.