Association Between Body Mass Index and Depression/Anxiety in an East Asian Population: A Mendelian Randomization...

Obesity and psychiatric disorders are the leading causes of global morbidity. Epidemiological studies suggest a bidirectional link between higher body mass index (BMI) and mental health outcomes, but the direction of causality remains uncertain due to confounding and reverse causation. We performed a Mendelian randomization (MR) analysis using genetic instruments for BMI (13 and 17 single-nucleotide polymorphisms [SNPs] identified in the Taiwan Biobank) from 107,191 Taiwanese adults (4855 "cases" with depression or anxiety and 102,336 "controls") to examine the association between BMI and depression and anxiety symptoms. The primary MR results revealed an inverse causal association between the two. An inverse-variance weighted analysis using 17 SNPs indicated that each one-unit increase in genetically predicted BMI was associated with a lower risk of depression and anxiety symptoms. Analyses restricted to 13 strong BMI-associated SNPs revealed a similar inverse direction of effect. The results suggest that higher BMI may be associated with a reduced risk of psychiatric disorders in this East Asian population, highlighting potential differences by population or underlying mechanism. These findings demonstrate how MR can clarify complex exposure-outcome relationships and highlight the need to explore the biological and psychosocial pathways connecting adiposity and mental health.