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Depress Anxiety. 2019 Dec;36(12):1154-1162. doi: 10.1002/da.22963. Epub 2019 Oct 14.

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

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Australian Centre for Precision Health, University of South Australia Cancer Research Institute, Adelaide, Australia.
Department of Pharmacology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences and Institute for Cardiovascular and Metabolic Research (ICMR), University of Reading, Reading, UK.
Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, UK.
South Australian Health and Medical Research Institute, Adelaide, Australia.



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.


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 .


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 ).


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.


BMI; MC4R; and UK Biobank; depression; gene-lifestyle factors interaction; genetic risk score; predisposition


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