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Depressive disorder moderates the effect of the FTO gene on body mass index

Molecular Psychiatry volume 17, pages 604–611 (2012)Cite this article

Abstract

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). In all, 8 of the top 10 single-nucleotide polymorphisms (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 seven SNPs in Radiant (P<0.0057), with PsyCoLaus giving supportive evidence for five SNPs (P-values between 0.03 and 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.

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Acknowledgements

We thank those who agreed to participate in the studies and the many colleagues who contributed to collection and phenotypic characterisation of the clinical samples, to genotyping and to statistical analyses. This study was funded by the Medical Research Council, UK and GlaxoSmithKline (G0701420). The GENDEP study was funded by a European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. This research was supported by a Marie Curie Intra European Fellowship within the 7th European Community Framework Programme. Dr Cohen-Woods and Dr Schosser were both funded by Postdoctoral Fellowships from the National Institute for Health Research (NIHR) specialist Biomedical Research Centre for Mental Health. Dr Rucker is funded by a Research Training Fellowship from the Wellcome Trust. The CoLaus/PsyCoLaus study was supported by grants from the Swiss National Science Foundation (#3200B0–105993, #3200B0-118308, 33CSC0-122661) and from GlaxoSmithKline. S Bergmann is grateful for financial support from the Giorgi-Cavaglieri Foundation, the Swiss National Science Foundation (Grant #3100AO-116323/1), the Swiss Institute of Bioinformatics and the European Framework Project 6 (through the AnEuploidy and EuroDia projects).

Author information

Authors and Affiliations

  1. MRC SGDP Centre, Institute of Psychiatry, King's College London, Denmark Hill, London, UK

    M Rivera, S Cohen-Woods, G Breen, M Y Ng, A W Butler, J Rucker, A Schosser, K J Aitchison, R Uher, I W Craig, C M Lewis, A E Farmer & P McGuffin

  2. CIBERSAM, University of Granada, Section of Psychiatry, Institute of Neurosciences, Biomedical Research Centre (CIBM), Granada, Spain

    M Rivera

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

    K Kapur & S Bergmann

  4. Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Cardiff, UK

    N Craddock

  5. Department of Psychiatry, Trinity Centre for Health Sciences, St James's Hospital, Dublin, Ireland

    M Gill

  6. Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine, Queen Mary University of London, Centre for Psychiatry, London, UK

    A Korszun

  7. Department of Psychiatry, University of Bonn, Bonn, Germany

    W Maier

  8. Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark

    O Mors

  9. Department of Psychological Medicine and Neurology, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Heath Park, UK

    M J Owen

  10. Department of Adult Psychiatry, University Hospital and Univeristy of Lausanne, Prilly-Lausanne, Switzerland

    M Preisig

  11. Genetics Division, Drugs Discovery, GlaxoSmithKline Research and Development, Verona, Italy

    F Tozzi

  12. Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA

    J Rice

  13. Central Institute of Mental Health, Mannheim, Germany

    M Rietschel

  14. Department of Psychiatry and Psychotherapy, Medical University Vienna, Vienna, Austria

    A Schosser

  15. Department of Medical and Molecular Genetics, School of Medicine, King's College London, London, UK

    C M Lewis

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  1. M Rivera
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Corresponding author

Correspondence to M Rivera.

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Competing interests

Aitchison, Farmer and McGuffin have received consultancy fees and honoraria for participating in expert panels for pharmaceutical companies including GlaxoSmithKline. Aitchison declares interests through the advisory boards for Johnson & Johnson, Lundbeck, Roche Diagnostics and Bristol-Myers Squibb; membership of Bristol-Myers Squibb UK Steering group 2003 to present; consultancy work for Roche Diagnostics, Johnson & Johnson Pharmaceutical Research and Development, Lundbeck, and Bristol-Myers Squibb Pharmaceuticals Limited; grants awarded by Johnson & Johnson Pharmaceutical Research and Development, Bristol-Myers Squibb Pharmaceuticals Limited, and E Merck Pharmaceuticals. Maier is member of the Advisory Boards/has received fees for speaking from: Lilly, Lundbeck. Tozzi was full-time employee of GlaxoSmithKline at the time when the work was performed. All other authors declare no conflicts of interest.

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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

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