Genetic Predisposition to High BMI Increased Among People With Depression

Genetic predisposition to high BMI was increased among people with depression, suggesting that depression might increase the expression of an individual’s genetic disposition to obesity.

Individuals with major depressive disorder (MDD) have been shown to have a greater genetic predisposition to higher body mass index (BMI) than those without depression, according to a study recently published in Depression and Anxiety. Study analyses also revealed that the melanocortin 4 receptor gene may play a critical role in the association between depression and obesity.

This study included data on 251,125 individuals sourced from the UK Biobank, all of whom were of white British ancestry and had complete data available on depression, BMI, and genotypes. The control group consisted of individuals with no history of depression. A genetic risk score for MDD was formulated to quantify the causal correlation between depression and BMI, with Mendelian randomization used to model the change in effect size per quantity of alleles linked with increased risk. The study researchers also investigated the potential association between depression and genetic risk score for BMI. 

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Depression was associated with BMI, with individuals with depression showing a 0.19 standard deviation ([SD] 95% CI, 0.18-0.20) higher BMI than individuals without depression (P =5.0 × 10²¹⁵); Mendelian randomization showed a greater genetic risk for depression with higher BMI (odds ratio [OR], 0.09 SD; 95% CI, 0.04-0.13; P =.0001). Those with depression had higher genetic susceptibility to BMI than controls (P =9.1×10⁴). Carrying 10 additional risk-increasing alleles was linked with 0.24 SD (95% CI, 0.23-0.25) higher BMI in individuals with depression and 0.20 SD (95% CI, 0.19-0.21) higher BMI in controls, translating to an additional 3.4 kg and 2.8 kg for an individual 1.73 m tall, respectively. The melanocortin 4 receptor gene variant rs6567160, a variant linked with BMI and obesity, was found to have the strongest influence on this interaction (P =5.7×10⁵).

Limitations of this study include a study population that was relatively healthier than the general population, as well as the potential for unmeasured confounding factors.

The study researchers concluded, “Our study provides genetic evidence for causal effect of depression on BMI.”  They added that those with depression are more genetically predisposed to high BMI than those without, “suggesting that depression might [increase] the expression of an individual’s genetic disposition to obesity.” Furthermore, researchers suggested the “role of [the melanocortin 4 receptor gene] in the link between depression and obesity,” highlighting this gene as a possible target for medication regimens in the treatment of obesity.


Mulugeta A, Zhou A, Vimaleswaran KS, Dickson C, Hyppönen E. Depression increases the genetic susceptibility to high body mass index: Evidence from UK Biobank [published online October 14, 2019]. Depress Anxiety. doi:10.1002/da.22963