Genome-wide association study and polygenic risk score analysis for schizophrenia in a Korean population

Abstract

Although large-scale genome-wide association studies (GWASs) have revealed the genetic architecture of schizophrenia, these studies have mainly focused on populations of European ancestry. This study aimed to identify common genetic variants associated with schizophrenia in the Korean population and evaluate the performance of polygenic risk scores (PRSs) derived from large-scale GWASs across ancestries. In the Korean psychiatric GWAS project (KPGP), seven academic institutes and their affiliated hospitals across South Korea recruited a cohort of 1670 patients with DSM-IV-defined schizophrenia and 2271 healthy controls. A total of 6690,822 SNPs were tested for association with schizophrenia. We identified one previously unreported genome-wide significant locus rs2423464 (P = 2.83 × 10⁻¹¹; odds ratio = 1.65; 95 % confidence interval = 1.43–1.91, minor allele frequency = 0.126). This variant was also associated with increased lysosomal-associated membrane protein family member 5 (LAMP5) gene expression. The PRS derived from the meta-analysis results of East Asian and European GWASs explained a larger proportion of the phenotypic variance in the Korean schizophrenia sample than the PRS of an East Asian or European GWAS. (R² = 0.073 for meta-analysis; 0.028 for East Asian GWAS; 0.037 for European GWAS). GWASs involving diverse ethnic groups will expand our understanding of the genetic architecture of schizophrenia.