The Causal Role of Adiposity in Mental Illness: A Systematic Review and Meta-Analysis of Mendelian Randomization Studies.
Min Gao, Paul J Doody, Dimitrios A Koutoukidis et al.
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In 30 seconds
This systematic review and meta-analysis assessed Mendelian randomization studies of adiposity and mental illness. The review included 57 studies with 215 MR estimates; 23 studies with 44 estimates contributed to meta-analyses. Pooled results suggested a modest causal association between general adiposity and depression (OR: 1.09, 95% CI, 1.02-1.15, p < 0.001), with high heterogeneity (I 2 = 94%). No sex difference was detected. Associations with schizophrenia and obsessive compulsive disorder were suggestive but imprecise and heterogeneous; evidence for other mental illnesses remained unclear.
Key findings
- General adiposity was associated with depression in pooled MR estimates (OR: 1.09, 95% CI, 1.02-1.15, p < 0.001; I 2 = 94%).
- Subgroup analysis found no evidence of a sex difference in the adiposity–depression relationship (p = 0.318).
- Evidence linking adiposity to schizophrenia and OCD was suggestive, but analyses had high imprecision and heterogeneity.
Why it matters
The findings add genetic-instrument evidence that general adiposity may contribute to depression, while underscoring that the estimated effect is modest and results vary substantially across studies. This distinction matters when interpreting links between weight and mental health: evidence for depression is stronger than for the other conditions assessed, but the review does not establish broad mental-health effects of adiposity.
What to keep in mind
The depression meta-analysis showed high heterogeneity (I 2 = 94%); evidence for schizophrenia and OCD was imprecise and heterogeneous, and evidence for other mental illnesses remained unclear.