Journal Article

The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression

Mohan, V, Wang, X, Pare, G, Diaz, R, Bergmann, S, Meyre, D, Thabane, L, Preisig, M, Anand, S, Yusuf, S, Zhang, X, Liu, L, Samaan, Z, Cohen-Woods, S, Gerstein, H, Rivera, M, Engert, J C, Craig, I, Corre, T, Waeber, G, Vollenweider, P, Xie, C, Kutalik, Z, Desai, D

2013

Overview

Candidate gene and genome-wide association studies have not identified common variants, which are reliably associated with depression. The recent identification of obesity predisposing genes that are highly expressed in the brain raises the possibility of their genetic contribution to depression. As variation in the intron 1 of the fat mass- and obesity-associated ( FTO ) gene contributes to polygenic obesity, we assessed the possibility that FTO gene may contribute to depression in a cross-sectional multi-ethnic sample of 6561 depression cases and 21 932 controls selected from the EpiDREAM, INTERHEART, DeCC (depression case–control study) and Cohorte Lausannoise (CoLaus) studies. Major depression was defined according to DSM IV diagnostic criteria. Association analyses were performed under the additive genetic model. A meta-analysis of the four studies showed a significant inverse association between the obesity risk FTO rs9939609 A variant and depression (odds ratio=0.92 (0.89, 0.97), P =3 × 10 −4 ) adjusted for age, sex, ethnicity/population structure and body-mass index (BMI) with no significant between-study heterogeneity ( I 2 =0%, P =0.63). The FTO rs9939609 A variant was also associated with increased BMI in the four studies (β 0.30 (0.08, 0.51), P =0.0064) adjusted for age, sex and ethnicity/population structure. In conclusion, we provide the first evidence that the FTO rs9939609 A variant may be associated with a lower risk of depression independently of its effect on BMI. This study highlights the potential importance of obesity predisposing genes on depression.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/208/726/649 / 631/208/727/2000 / 692/699/2743/393 / 692/699/476/1414 / Adult and adolescent clinical studies / Age composition / Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Association analysis / Behavioral Sciences / Biological and medical sciences / Biological Psychology / Body fat / Depression / Depression - genetics / Depression, Mental / Depressive Disorder, Major - genetics / Ethnicity / Female / Fto gene / Genes / Genetic analysis / Genetic aspects / Genetic Predisposition to Disease - genetics / Genome-wide association studies / Genomes / Genotype / Humans / Male / Medical sciences / Medicine / Medicine & Public Health / Mental depression / Metabolic diseases / Middle Aged / Minority & ethnic groups / Miscellaneous / Mood disorders / Neurosciences / Obesity / Obesity - genetics / Obesity gene / original-article / Pharmacotherapy / Phenotype / Polymorphism, Single Nucleotide - genetics / Population structure / Properties / Proteins - genetics / Psychiatry / Psychological aspects / Psychology. Psychoanalysis. Psychiatry / Psychopathology. Psychiatry / Systematic review