Genome-wide association study of schizophrenia in a Chinese population

Abstract

Schizophrenia is a severe psychiatric disease with a lifetime risk of approximately 1%. Although the heritability of schizophrenia is high, very few susceptibility genes have been identified to date. Genome-wide association study (GWAS) has proved to be a powerful tool in dissecting the genetic basis of complex diseases. To date, most GWAS on schizophrenia were conducted on Caucasians. However, allele frequencies, linkage disequilibrium patterns and genetic or environmental backgrounds may differ among populations, rendering some variants more readily discovered in one population than the other. We have performed a GWAS on schizophrenia with 400 cases and 1311 controls in a Chinese Han population. Samples were genotyped using the Illumina Human610-Quad BeadChip. After quality control procedures, the dataset consisted of 477354 SNPs from 396 cases and 1286 controls. In total 67 SNPs achieved nominal p-values less than 1E-4. We also extracted the association results of SNPs lying within 30 candidate genes listed in the SZgene database. The QQ plot however shows no evidence of enrichment of significant variants within these candidate genes. The most significant SNP in the candidate gene analysis belongs to the DISC1 gene with a p-value of 8.21E-4. We plan to perform a replication study in an independent sample of family trios from Chengdu, China. In addition to selecting SNPs reaching the highest significance levels in the whole-genome scan, we also plan to select top SNPs in the linkage hotspots suggested by a recent meta-analysis. We will adopt a more liberal threshold for SNPs lying within linkage regions than the other SNPs in the genome, as the former group probably has stronger prior evidence for association.