| Title: | Higher adiposity and mental health: causal inference using Mendelian randomization |
| Journal: | Human Molecular Genetics |
| Published: | 16 Jul 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34270736/ |
| DOI: | https://doi.org/10.1093/hmg/ddab204 |
| URL: | https://academic.oup.com/hmg/article-pdf/30/24/2371/41389768/ddab204.pdf |
| Citations: | 35 (20 in last 2 years) as of 8 Aug 2024 |
Publication 5138
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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.</p>
11 Authors
- Francesco Casanova
- Jessica O'Loughlin
- Susan Martin
- Robin N Beaumont
- Andrew R Wood
- Edward R Watkins
- Rachel M Freathy
- Saskia P Hagenaars
- Timothy M Frayling
- Hanieh Yaghootkar
- Jess Tyrrell
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