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

Area of Science:

• Genetics
• Psychiatry
• Metabolic Health

Background:

• Previous research indicates a correlation between lower Body Mass Index (BMI) and increased risk of Obsessive-Compulsive Disorder (OCD).
• However, the etiological relevance of other body composition metrics, such as fat mass (FM), remains less understood in relation to OCD.
• This study investigates the potential causal link between body fat mass and OCD risk.

Purpose of the Study:

• To determine the causal association between genetically predicted body fat mass (FM) and the risk of developing Obsessive-Compulsive Disorder (OCD).
• To explore whether body fat mass is a more relevant indicator than BMI in the etiology of OCD.
• To provide evidence for targeted interventions in mental health that consider body composition.

Main Methods:

• Utilized two-sample Mendelian randomization analysis on genome-wide association study summary statistics from European ancestry populations.
• Employed inverse variance weighting and weighted median approaches to estimate the causal effect of FM on OCD risk.
• Conducted heterogeneity, horizontal pleiotropy, and sensitivity analyses to ensure the robustness and reliability of the findings.

Main Results:

• A genetically predicted decrease in body fat mass (FM) was found to be causally associated with an increased risk of Obsessive-Compulsive Disorder (OCD) [OR=0.680, P=0.003].
• Each standard deviation increase in genetically predicted body fat percentage corresponded to a reduced OCD risk [OR=0.638, P=0.009].
• Sensitivity analyses confirmed the robustness of these results, with no significant outliers detected.

Conclusions:

• There is a significant negative causal association between body fat mass (FM) and the risk of Obsessive-Compulsive Disorder (OCD).
• These findings highlight the importance of considering body composition and fat distribution, beyond just BMI, in the prevention and treatment of mental disorders like OCD.
• Future mental health strategies may benefit from incorporating interventions targeting body fat regulation.