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.