Multiple risk variants of
schizophrenia have 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 of
schizophrenia. However, less replication studies have been reported. Our objective was to investigate the association between CAMs pathway and
schizophrenia in the Chinese Han population. We first performed a pathway analysis utilizing our previous GWAS data. The CAMs pathway (hsa04514) was significantly associated with
schizophrenia using hybrid gene set-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 and
ICAM3) were modestly significantly associated with
schizophrenia (P<0.01). Then, we selected one promising gene
neuroligin 1 (NLGN1) to further investigate the association between eight significant SNPs and
schizophrenia in an independent sample (1814
schizophrenia cases and 1487 healthy controls). Our study showed that seven SNPs of NLGN1 and two haplotype blocks were significantly associated with
schizophrenia. This association was confirmed by the results of combined analysis. Among them, SNP rs9835385 had the most significant association with
schizophrenia (
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 with
schizophrenia in pathway-level and identified one susceptibility gene NLGN1. Further investigation of the roles of CAMs pathway in the pathogenesis of
schizophrenia is warranted.