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PLoS One. 2015 Dec 16;10(12):e0144719. doi: 10.1371/journal.pone.0144719. eCollection 2015.

Evidence for Association of Cell Adhesion Molecules Pathway and NLGN1 Polymorphisms with Schizophrenia in Chinese Han Population.

Zhang Z1,2, Yu H3,4, Jiang S1,2, Liao J1,2, Lu T1,2, Wang L1,2, Zhang D1,2,4,5, Yue W1,2.

Author information

Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.
Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
School of Life Sciences, Tsinghua University, Beijing, China.
Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China.
PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.


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.

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