Causal Associations Between Body Mass Index and Mental Health: A Mendelian Randomization Study

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Abstract

Abstract Background Body Mass Index (BMI) is negatively correlated with subjective well-being and positively correlated with depressive symptoms. Whether these associations reflect causal effects or confounding is unclear. Methods We examined causal effects between BMI and subjective well-being/depressive symptoms with bi-directional, two-sample Mendelian randomization using summary-level data from large genome-wide association studies. Genetic variants robustly related to the exposure variable acted as instrumental variable (two thresholds were used; p <5e-08 and p <1e-05). These ‘instruments’ were then associated with the outcome variable. Pleiotropy was corrected for by two sensitivity analyses. Results Substantial evidence was found for a causal effect of BMI on mental health, such that a higher BMI decreased subjective well-being and increased depressive symptoms. No consistent evidence was found for causality in the other direction. Conclusions This study provides support for a higher BMI causing poorer mental health. Further research should corroborate these findings and consider non-linear effects and sex differences.

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