Replicated association between the European GWAS locus rs10503253 at CSMD1 and schizophrenia in Asian population

Abstract

Schizophrenia is one of the most severe mental disorders with significant heritability. Recent genetic association studies including genome-wide association studies (GWAS) have identified multiple common variants conferring risk of schizophrenia. An intronic SNP within CSMD1, rs10503253, is one of the top risk SNPs for schizophrenia in Europeans discovered through large GWAS. However, whether rs10503253 is also a risk SNP for schizophrenia in other populations, such as Asians, is still unknown. To answer this question, we examined the association of rs10503253 with schizophrenia in a total of 7514 schizophrenia patients, 9058 healthy controls and 1115 nuclear families originated from Asia using a meta-analytic approach. In the meta-analysis of all the samples, we confirmed the association of rs10503253 A-allele with schizophrenia in Asian population (P-value=0.0093, odds ratio=1.062, 95% confidence interval=1.015-1.111), and no genetic heterogeneity between individual samples (P=0.810) was observed. Using the "Leave-one-out" sensitivity analysis, we further confirmed the association between rs10503253 and schizophrenia. These data show that rs10503253 is likely a common schizophrenia risk variant in multiple ethnic groups, and further studies regarding the underlying molecular mechanisms are needed.

Keywords: Asian; CSMD1; Meta-analysis; Schizophrenia; rs10503253.