Common variants on 8p12 and 1q24.2 confer risk of schizophrenia

Abstract

Schizophrenia is a severe mental disorder affecting ∼1% of the world population, with heritability of up to 80%. To identify new common genetic risk factors, we performed a genome-wide association study (GWAS) in the Han Chinese population. The discovery sample set consisted of 3,750 individuals with schizophrenia and 6,468 healthy controls (1,578 cases and 1,592 controls from northern Han Chinese, 1,238 cases and 2,856 controls from central Han Chinese, and 934 cases and 2,020 controls from the southern Han Chinese). We further analyzed the strongest association signals in an additional independent cohort of 4,383 cases and 4,539 controls from the Han Chinese population. Meta-analysis identified common SNPs that associated with schizophrenia with genome-wide significance on 8p12 (rs16887244, P = 1.27 × 10(-10)) and 1q24.2 (rs10489202, P = 9.50 × 10(-9)). Our findings provide new insights into the pathogenesis of schizophrenia.

Figure 1

Regional plots of the 2 schizophrenia loci (8p12 and 1q24.2). Results (−log10 P) are shown for SNPs for the region flanking 350 kb on either side of the marker SNPs. P_{gwas_meta} is for the combined results of the three initial datasets, represented by the circle (for genotyped SNPs) and the triangle (for imputed SNPs), and P_{biox_meta} is for the combined results of the initial and follow-up dataset (BIOX), represented by the diamond. The marker SNP is shown in purple and the r² values of the rest of the SNPs are indicated by different colors. The genes within the relevant region are annotated and shown as arrows. The D′ LD block structure of the related surrounding region according to the CHB+JPT HapMap data are provided at the bottom.

Figure 1

Regional plots of the 2 schizophrenia loci (8p12 and 1q24.2). Results (−log10 P) are shown for SNPs for the region flanking 350 kb on either side of the marker SNPs. P_{gwas_meta} is for the combined results of the three initial datasets, represented by the circle (for genotyped SNPs) and the triangle (for imputed SNPs), and P_{biox_meta} is for the combined results of the initial and follow-up dataset (BIOX), represented by the diamond. The marker SNP is shown in purple and the r² values of the rest of the SNPs are indicated by different colors. The genes within the relevant region are annotated and shown as arrows. The D′ LD block structure of the related surrounding region according to the CHB+JPT HapMap data are provided at the bottom.