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A Genetic Risk Score Combining 32 SNPs is Associated with Body Mass Index and Improves Obesity Prediction in People with Major Depressive Disorder

Hung, C. and Breen, G. and Czamara, D. and Corre, T. and Wolf, C. and Kloiber, S. and Bergmann, S. and Craddock, N. and Gill, M. and Holsboer, F. and Jones, Lisa and Jones, I. and Korszun, A. and Kutalik, Z. and Lucae, S. and Maier, W. and Mors, O. and Owen, M.J. and Rice, J. and Rietschel, M. and Uher, R. and Vollenweider, P. and Waeber, G. and Craig, I.W. and Farmer, A.E. and Lewis, C.M. and Müller-Myhsok, B. and Preisig, M. and McGuffin, P. and Rivera, M. (2015) A Genetic Risk Score Combining 32 SNPs is Associated with Body Mass Index and Improves Obesity Prediction in People with Major Depressive Disorder. BMC Medicine, 13 (86). pp. 1-10. ISSN Online: 1741-7015

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Abstract

BACKGROUND: Obesity is strongly associated with major depressive disorder (MDD) and various other diseases. Genome-wide association studies have identified multiple risk loci robustly associated with body mass index (BMI). In this study, we aimed to investigate whether a genetic risk score (GRS) combining multiple BMI risk loci might have utility in prediction of obesity in patients with MDD. METHODS: Linear and logistic regression models were conducted to predict BMI and obesity, respectively, in three independent large case-control studies of major depression (Radiant, GSK-Munich, PsyCoLaus). The analyses were first performed in the whole sample and then separately in depressed cases and controls. An unweighted GRS was calculated by summation of the number of risk alleles. A weighted GRS was calculated as the sum of risk alleles at each locus multiplied by their effect sizes. Receiver operating characteristic (ROC) analysis was used to compare the discriminatory ability of predictors of obesity. RESULTS: In the discovery phase, a total of 2,521 participants (1,895 depressed patients and 626 controls) were included from the Radiant study. Both unweighted and weighted GRS were highly associated with BMI (P < 0.001) but explained only a modest amount of variance. Adding 'traditional' risk factors to GRS significantly improved the predictive ability with the area under the curve (AUC) in the ROC analysis, increasing from 0.58 to 0.66 (95% CI, 0.62-0.68; χ(2) = 27.68; P < 0.0001). Although there was no formal evidence of interaction between depression status and GRS, there was further improvement in AUC in the ROC analysis when depression status was added to the model (AUC = 0.71; 95% CI, 0.68-0.73; χ(2) = 28.64; P <0.0001). We further found that the GRS accounted for more variance of BMI in depressed patients than in healthy controls. Again, GRS discriminated obesity better in depressed patients compared to healthy controls. We later replicated these analyses in two independent samples (GSK-Munich and PsyCoLaus) and found similar results. CONCLUSIONS: A GRS proved to be a highly significant predictor of obesity in people with MDD but accounted for only modest amount of variance. Nevertheless, as more risk loci are identified, combining a GRS approach with information on non-genetic risk factors could become a useful strategy in identifying MDD patients at higher risk of developing obesity.

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Uncontrolled Keywords: body mass index, genetic risk score, major depressive disorder, obesity
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Academic Departments > Institute of Health and Society
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Copyright Info: Open Access article
Depositing User: Lisa Jones
Date Deposited: 17 Dec 2015 08:51
Last Modified: 17 Dec 2015 08:51
URI: https://eprints.worc.ac.uk/id/eprint/4074

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