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Updated: Apr 1, 2026

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
Genetic evidence for the association between schizophrenia and obesity
Mei-Hsin Su1,2, Tzu-Chen Yeh2,3, Chi-Fung Cheng4
1Department of Psychiatry, Virginia Institute for Psychiatric Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Objective:
Observational studies found that individuals with schizophrenia (SCZ) exhibit higher prevalence of obesity-related traits, posing significant health risks. However, the neuropsychiatric mechanism remains unclear. This study aimed to investigate the genetic connections between schizophrenia and obesity.
Methods:
We examined the effect of genetic liability for SCZ on obesity in Taiwan Biobank samples of East Asian populations (N = 106,614) using linear regression models. We also performed linkage disequilibrium score regression to estimate genetic correlation in East Asian and European populations, respectively, and conducted two-sample Mendelian randomization (MR) to infer their causality in European populations.
Results:
Our results indicated that higher genetic predisposition for SCZ was associated with lower body mass index (BMI) (beta±SE = -0.11 ± 0.01, per SD of genetic predisposition for SCZ), body fat percentage (BFP) (beta±SE = -0.16 ± 0.02), waist circumference (WC) (beta±SE = -0.20 ± 0.03), hip circumference (HC), (beta±SE = -0.17 ± 0.02) and waist-to-hip ratio (WHR) (beta±SE = -0.06 ± 0.02). SCZ showed negative genetic correlations with BMI (rg±SE = -0.15 ± 0.03 and -0.11 ± 0.01), WC (rg±SE = -0.10 ± 0.03 and -0.08 ± 0.02), and HC (rg±SE = -0.12 ± 0.03 and -0.08 ± 0.03) in both East Asian and European populations. SCZ showed negative genetic correlation with BFP in East Asian populations (rg±SE = -0.13 ± 0.03, p-value = 0.0001) but not in European populations (rg±SE = -0.02 ± 0.04, p-value = 0.62). MR analyses revealed negative causal relationships from SCZ to BMI, BFP, WC, and HC.
Conclusions:
This study clarified that the increased obesity prevalence in individuals with SCZ is not due to the genetic effect of SCZ itself. Rather, genetic variants associated with SCZ have a negative impact on both causality and correlations between SCZ and obesity.
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