Higher adiposity and mental health: causal inference using Mendelian randomization

Francesco Casanova, Jessica O’Loughlin, Robin N Beaumont, Andrew R Wood, Edward R Watkins, Rachel M Freathy, Saskia P Hagenaars, Timothy M Frayling, Hanieh Yaghootkar, Jess Tyrrell

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Higher adiposity is an established risk factor for psychiatric diseases including depression and anxiety. The associations between adiposity and depression may be explained by the metabolic consequences and/or by the psychosocial impact of higher adiposity. We performed one-and two-sample Mendelian randomization (MR) in up to 145 668 European participants from the UK Biobank to test for a causal effect of higher adiposity on 10 well-validated mental health and well-being outcomes derived using the Mental Health Questionnaire (MHQ). We used three sets of adiposity genetic instruments: (a) a set of 72 BMI genetic variants, (b) a set of 36 favourable adiposity variants and (c) a set of 38 unfavourable adiposity variants. We additionally tested causal relationships (1) in men and women separately, (2) in a subset of individuals not taking antidepressants and (3) in non-linear MR models. Two-sample MR provided evidence that a genetically determined one standard deviation (1-SD) higher BMI (4.6 kg/m2) was associated with higher odds of current depression [OR: 1.50, 95%CI: 1.15, 1.95] and lower well-being [ß:-0.15, 95%CI:-0.26,-0.04]. Findings were similar when using the metabolically favourable and unfavourable adiposity variants, with higher adiposity associated with higher odds of depression and lower well-being scores. Our study provides further evidence that higher BMI causes higher odds of depression and lowers well-being. Using genetics to separate out metabolic and psychosocial effects, our study suggests that in the absence of adverse metabolic effects higher adiposity remains causal to depression and lowers well-being.

Original languageEnglish
Pages (from-to)2371-2382
Number of pages12
JournalHuman Molecular Genetics
Volume30
Issue number24
Early online date16 Jul 2021
DOIs
Publication statusPublished - 15 Dec 2021

Keywords

  • Genetics(clinical)
  • Genetics
  • Molecular Biology
  • General Medicine

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