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

Molecular Psychiatry volume 18, pages 1281–1286 (2013)Cite this article

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A Corrigendum to this article was published on 05 March 2013

Abstract

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 (I2=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.

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Acknowledgements

Z Samaan is supported by a New Investigator Fund from Hamilton Health Sciences Foundation to carry out this study. D Meyre is supported by a Canada Research Chair. P McGuffin and AE Farmer, CM Lewis and G Breen contributed data to the study.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada

    Z Samaan, S Anand, G Pare, L Thabane, H Gerstein, G Waeber, S Yusuf & D Meyre

  2. Population Health Research Institute, Hamilton, ON, Canada

    Z Samaan, S Anand, X Zhang, D Desai, G Pare, L Thabane, C Xie, H Gerstein, S Yusuf & D Meyre

  3. MRC Social Genetic and Developmental Psychiatry Centre, London, UK

    M Rivera, I Craig & S Cohen-Woods

  4. University of Granada, Granada, Spain

    M Rivera

  5. McGill University,, Montreal, QC, Canada

    J C Engert

  6. Madras Diabetes Research Foundation, Chennai, India

    V Mohan

  7. ECLA—Academic Research Organization, Rosario, Argentina

    R Diaz

  8. Beijing Hypertension League Institute, Beijing, China

    X Wang & L Liu

  9. Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland

    T Corre, Z Kutalik & S Bergmann

  10. Swiss Institute of Bioinformatics, Lausanne, Switzerland

    T Corre, Z Kutalik & S Bergmann

  11. Department of Psychiatry, CHUV, Lausanne, Switzerland

    M Preisig

  12. Division of Internal Medicine, CHUV, Lausanne, Switzerland

    P Vollenweider

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  1. Z Samaan
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Correspondence to D Meyre.

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Samaan, Z., Anand, S., Zhang, X. et al. The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression. Mol Psychiatry 18, 1281–1286 (2013). https://doi.org/10.1038/mp.2012.160

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