Dissecting the Causal Association between Body Fat Mass and Obsessive-Compulsive Disorder: A Two-Sample Mendelian...

Previous studies link lower body mass index (BMI) with increased obsessive-compulsive disorder (OCD) risk, yet other body mass indicators may be more etioloically relevant. We dissected the causal association between body fat mass (FM) and OCD.

Summary statistics from genome-wide association studies of European ancestry were utilized to conduct two-sample Mendelian randomization analysis. Heterogeneity, horizontal pleiotropy, and sensitivity analyses were performed to assess the robustness.

The inverse variance weighting method demonstrated that a genetically predicted decrease in FM was causally associated with an increased OCD risk [odds ratio ( OR) = 0.680, 95% confidence interval ( CI): 0.528-0.875, P = 0.003]. Similar estimates were obtained using the weighted median approach ( OR = 0.633, 95% CI: 0.438-0.915, P = 0.015). Each standard deviation increases in genetically predicted body fat percentage corresponded to a reduced OCD risk ( OR = 0.638, 95% CI: 0.455-0.896, P = 0.009). The sensitivity analysis confirmed the robustness of these findings with no outlier instrument variables identified.

The negative causal association between FM and the risk of OCD suggests that the prevention or treatment of mental disorders should include not only the control of BMI but also fat distribution and body composition.