Body mass index and psychiatric disorders: a Mendelian randomization study

Obesity is a highly prevalent risk factor for cardiometabolic diseases. Observationalstudies suggest that obesity is associated with psychiatric traits, but causalinference from such studies has several limitations. We used two-sample Mendelianrandomization methods (inverse variance weighting, weighted median and MR-Eggerregression) to evaluate the association of body mass index (BMI) with threepsychiatric traits using data from the Genetic Investigation of AnthropometricTraits and Psychiatric Genomics consortia. Causal odds ratio estimates per1-standard deviation increment in BMI ranged from 0.88 (95% CI: 0.62; 1.25) to 1.23(95% CI: 0.65; 2.31) for bipolar disorder; 0.93 (0.78; 1.11) to 1.41 (0.87; 2.27)for schizophrenia; and 1.15 (95% CI: 0.92; 1.44) to 1.40 (95% CI: 1.03; 1.90) formajor depressive disorder. Analyses removing potentially influential SNPs suggestedthat the effect estimates for depression might be underestimated. Our findings donot support the notion that higher BMI increases risk of bipolar disorder andschizophrenia. Although the point estimates for depression were consistent in allsensitivity analyses, the overall statistical evidence was weak. However, the factthat SNP-depression associations were estimated in relatively small samples reducedpower to detect causal effects. This should be re-addressed when SNP-depressionassociations from larger studies become available.