Institute of Mental Health, Peking University, Beijing, China.
Nat Genet. 2011 Oct 30;43(12):1228-31. doi: 10.1038/ng.979.
To identify susceptibility loci for schizophrenia, we performed a two-stage genome-wide association study (GWAS) of schizophrenia in the Han Chinese population (GWAS: 746 individuals with schizophrenia and 1,599 healthy controls; validation: 4,027 individuals with schizophrenia and 5,603 healthy controls). We identified two susceptibility loci for schizophrenia at 6p21-p22.1 (rs1233710 in an intron of ZKSCAN4, P(combined) = 4.76 × 10(-11), odds ratio (OR) = 0.79; rs1635 in an exon of NKAPL, P(combined) = 6.91 × 10(-12), OR = 0.78; rs2142731 in an intron of PGBD1, P(combined) = 5.14 × 10(-10), OR = 0.79) and 11p11.2 (rs11038167 near the 5' UTR of TSPAN18, P(combined) = 1.09 × 10(-11), OR = 1.29; rs11038172, P(combined) = 7.21 × 10(-10), OR = 1.25; rs835784, P(combined) = 2.73 × 10(-11), OR = 1.27). These results add to previous evidence of susceptibility loci for schizophrenia at 6p21-p22.1 in the Han Chinese population. We found that NKAPL and ZKSCAN4 were expressed in postnatal day 0 (P0) mouse brain. These findings may lead to new insights into the pathogenesis of schizophrenia.
为了鉴定精神分裂症的易感性基因座，我们在汉族人群中进行了精神分裂症的两阶段全基因组关联研究（GWAS：GWAS 阶段包括 746 名精神分裂症患者和 1599 名健康对照者；验证阶段包括 4027 名精神分裂症患者和 5603 名健康对照者）。我们在 6p21-p22.1 上鉴定出两个与精神分裂症相关的易感基因座，分别为 ZKSCAN4 内含子中的 rs1233710（P(combined) = 4.76×10(-11)，OR = 0.79）和 NKAPL 外显子中的 rs1635（P(combined) = 6.91×10(-12)，OR = 0.78），以及 PGBD1 内含子中的 rs2142731（P(combined) = 5.14×10(-10)，OR = 0.79）和 11p11.2（TSPAN18 5'UTR 附近的 rs11038167，P(combined) = 1.09×10(-11)，OR = 1.29；rs11038172，P(combined) = 7.21×10(-10)，OR = 1.25；rs835784，P(combined) = 2.73×10(-11)，OR = 1.27）。这些结果为汉族人群中 6p21-p22.1 上的精神分裂症易感基因座提供了更多的证据。我们发现 NKAPL 和 ZKSCAN4 在出生后第 0 天（P0）的小鼠脑中表达。这些发现可能为精神分裂症的发病机制提供新的见解。
