¹National Health Research Institutes, National Center for Geriatrics and Welfare Research, Zhunan, Taiwan, ²Virginia Commonwealth University, Department of Psychiatry, Virginia Institute for Psychiatric Behavioral Genetics, Richmond, United States, ³China Medical University, Department of Public Health, Taichung, Taiwan, ⁴National Health Research Institutes, Center for Neuropsychiatric Research, Zhunan, Taiwan, ⁵Biogen, Biogen, Cambridge, United States

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.