| Abstract |
Multiple risk variants ofschizophreniahave been identified by Genome-wide association studies (GWAS). As a complement for GWAS, previous pathway-based analysis has indicated that cell adhesion molecules (CAMs) pathway might be involved in the pathogenesis ofschizophrenia. However, less replication studies have been reported. Our objective was to investigate the association between CAMs pathway andschizophreniain the Chinese Han population. We first performed a pathway analysis utilizing our previous GWAS data. The CAMs pathway (hsa04514) was significantly associated withschizophrenia使用混合基因集合based test (P = 1.03�10-10) and hypergeometric test (P = 5.04�10-6). Moreover, 12 genes (HLA-A, HLA-C, HLA-DOB, HLA-DPB1, HLA-DQA2, HLA-DRB1, MPZ, CD276, NLGN1, NRCAM, CLDN1 andICAM3) were modestly significantly associated withschizophrenia(P<0.01). Then, we selected one promising gene neuroligin 1 (NLGN1) to further investigate the association between eight significant SNPs andschizophreniain an independent sample (1814schizophreniacases and 1487 healthy controls). Our study showed that seven SNPs of NLGN1 and two haplotype blocks were significantly associated withschizophrenia. This association was confirmed by the results of combined analysis. Among them, SNP rs9835385 had the most significant association withschizophrenia(P = 2.83�10-7). Furthermore, in silico analysis we demonstrated that NLGN1 is preferentially expressed in human brain and SNP rs1488547 was related to the expression level. We validated the association of CAMs pathway withschizophreniain pathway-level and identified one susceptibility gene NLGN1. Further investigation of the roles of CAMs pathway in the pathogenesis ofschizophreniais warranted. |