Polygenic risk scores analyses of psychiatric and metabolic traits with antipsychotic-induced weight gain in schizophrenia: an exploratory study

Pharmacogenomics J. 2023 Sep;23(5):119-126. doi: 10.1038/s41397-023-00305-y. Epub 2023 Apr 27.


Given the polygenic nature of antipsychotic-induced weight gain (AIWG), we investigated whether polygenic risk scores (PRS) for various psychiatric and metabolic traits were associated with AIWG. We included individuals with schizophrenia (SCZ) of European ancestry from two cohorts (N = 151, age = 40.3 ± 11.8 and N = 138, age = 36.5 ± 10.8). We investigated associations of AIWG defined as binary and continuous variables with PRS calculated from genome-wide association studies of body mass index (BMI), coronary artery disease (CAD), fasting glucose, fasting insulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, type 1 and 2 diabetes mellitus, and SCZ, using regression models. We observed nominal associations (uncorrected p < 0.05) between PRSs for BMI, CAD, and LDL-C, type 1 diabetes, and SCZ with AIWG. While results became non-significant after correction for multiple testing, these preliminary results suggest that PRS analyses might contribute to identifying risk factors of AIWG and might help to elucidate mechanisms at play in AIWG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents* / adverse effects
  • Cholesterol, LDL / genetics
  • Coronary Artery Disease* / drug therapy
  • Diabetes Mellitus, Type 1* / chemically induced
  • Diabetes Mellitus, Type 1* / drug therapy
  • Diabetes Mellitus, Type 2* / drug therapy
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Middle Aged
  • Multifactorial Inheritance / genetics
  • Risk Factors
  • Schizophrenia* / drug therapy
  • Schizophrenia* / genetics
  • Weight Gain / genetics


  • Antipsychotic Agents
  • Cholesterol, LDL