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

Rivera, M., Cohen-Woods, S., Kapur, K., Breen, G., Ng, M. Y., Butler, A. W., Craddock, Nicholas John, Gill, M., Korszun, A., Maier, W., Mors, O., Owen, Michael John, Preisig, M., Bergmann, S., Tozzi, F., Rice, J., Rietschel, M., Rucker, J., Schosser, A., Aitchison, K. J., Uher, R., Craig, I. W., Lewis, C. M., Farmer, A. E. and McGuffin, P. 2011. Depressive disorder moderates the effect of the FTO gene on body mass index. Molecular Psychiatry 17 (6) , pp. 604-611. 10.1038/mp.2011.45

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RZ Other systems of medicine
Uncontrolled Keywords: depression; FTO gene; obesity; BMI; body mass index
Publisher: Nature Publishing Group
ISSN: 1359-4184
Last Modified: 04 Jun 2017 03:56

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