Depression increases the genetic susceptibility to high body mass index: evidence from UK Biobank

Mulugeta, A., Zhou, A., Vimaleswaran, K. S. ORCID: https://orcid.org/0000-0002-8485-8930, Dickson, C. and Hyppönen, E. (2019) Depression increases the genetic susceptibility to high body mass index: evidence from UK Biobank. Depression and Anxiety, 36 (12). pp. 1154-1162. ISSN 1520-6394 doi: 10.1002/da.22963

Abstract/Summary

Background This study aimed to explore the association between depression and body mass index (BMI), and to investigate whether genetic susceptibility to high BMI is different among individuals with or without depression. Methods We used data on 251,125 individuals of white British ancestry from the UK Biobank. We conducted Mendelian randomization (MR) analysis to test for a causal association between depression and BMI using a major depressive disorder (MDD)‐related genetic risk score (GRSMDD) as an instrument for depression. We also examined whether depression modifies genetic susceptibility to high BMI, by investigating the interaction between depression and the BMI‐related GRSBMI. Results We found observational and genetic evidence for an association between depression and BMI (MR beta: 0.09, 95% confidence interval [CI] 0.04–0.13). Further, the contribution of genetic risk to high BMI was higher among individuals with depression compared to controls. Carrying 10 additional BMI increasing alleles was associated with 0.24 standard deviation (SD; 95%CI 0.23–0.25) higher BMI among depressed individuals compared to 0.20 SD (95%CI 0.19–0.21) higher in controls, which corresponds to 3.4 kg and 2.8 kg extra weight for an individual of average height. Amongst the individual loci, the evidence for interaction was most notable for a variant near MC4R, a gene known to affect both appetite regulation and the hypothalamic‐pituitary adrenal axis (pinteraction = 5.7 × 10−5). Conclusion Genetic predisposition to high BMI was higher among depressed than to nondepressed individuals. This study provides support for a possible role of MC4R in the link between depression and obesity.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/87010
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences
Uncontrolled Keywords	BMI, MC4R, and UK Biobank, depression, gene-lifestyle factors interaction, genetic risk score, predisposition
Publisher	Wiley
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