235. GENETIC EVIDENCE FOR THE ASSOCIATION BETWEEN SCHIZOPHRENIA AND OBESITY

Abstract Background Observational studies found that individuals with schizophrenia exhibit higher prevalence of obesity-related traits, posing significant health risks. However, the neuropsychiatric mechanism remains unclear. Aims & Objectives To investigate the genetic connections between schizophrenia and obesity. Method We examined the effect of genetic liability for schizophrenia on obesity in Taiwan Biobank samples of East Asian populations (N=106,614) using linear regression models. We also estimated the genetic correlation using linkage disequilibrium score regression and conducted Mendelian randomization (MR) to infer their causality among European populations. Results Our results indicated that higher genetic predisposition for schizophrenia reduced the risk of body mass index (BMI), body fat percentage (BFP), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). Genetic correlations were negatively correlated between schizophrenia and BMI, WC, HC, and WHR. MR analysis revealed negative causal relationships from schizophrenia to BMI, BFP, WC, and HC, as well as from BMI and WHR to schizophrenia. Discussion & Conclusions This study clarified that the increased obesity prevalence in individuals with schizophrenia is not due to the genetic effect of schizophrenia itself. Rather, genetic variants associated with schizophrenia have a negative impact on both causality and correlations between schizophrenia and obesity.