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

an article by Anwar Mulugeta (University of South Australia Cancer Research Institute, Adelaide, Australia; Addis Ababa University, Ethiopia). Ang Zhou and Cameron Dickson (University of South Australia Cancer Research Institute, Adelaide, Australia), Karani S. Vimaleswaran (University of Reading, UK) and Elina Hyppönen (University of South Australia Cancer Research Institute, Adelaide, Australia; UCL Great Ormond Street Institute of Child Health, London, UK; South Australian Health and Medical Research Institute, Adelaide, Australia_ published in Depression and Anxiety Volume 36 Issue 12 (December 2019)

Abstract

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.

---