title: Polymorphism of rs3737597 in DISC1 Gene on Chromosome 1q42.2 in sALS Patients: a Chinese Han Population Case-Control Study.
abstract: Although lots of genes have been revealed to relate to sporadic amyotrophic lateral sclerosis (sALS), its genetic mechanisms still need to be further explored. We aimed to search the novel genetic factors of sALS and assess their contribution. We constructed an integrative dataset based on the 3227 subsignificant genes (P value < 0.01) from two sALS-related genome-wide association studies (GWAS) (the US and Irish studies). A significant replication between both studies was confirmed by the gene set enrichment analysis in the integral level (P value < 10-4). Using the pathway overrepresentation analysis, we revealed the 34 shared Gene Ontology (GO) biological processes from the two independent studies (P value < 0.01). Among these pathways, the nervous system developmental pathway (NSD function, GO:0007399) was further supported by the previously reported genes related to sALS (P value = 3.28e-12). Importantly, four of 17 NSD-function-related target genes (disrupted-in-schizophrenia-1 (DISC1), CNTN4, NRXN3, and ERBB4) presented a considerable association with sALS in both studies. To further verify the association between the NSD function target genes and sALS, we preformed a two-stage case-control study based on 500 sALS patients and 500 controls of Chinese Han populations from mainland. A polymorphism of rs3737597 in DISC1 gene involved in the nervous system developmental pathway was closely associated with sALS. The nervous system developmental pathway is a potential pathogenesis of sALS, among them, the polymorphism of rs3737597 in DISC1 might play some roles.
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, 330031, Jiangxi, China.|College of Basic Medical Science, Nanchang University, Nanchang, 330006, Jiangxi, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Deng
authors.affiliation: School of Public Health, Nanchang University, Nanchang, 330006, Jiangxi, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Huo
authors.affiliation: Department of Neurology, the first affiliated hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.|College of Basic Medical Science, Nanchang University, Nanchang, 330006, Jiangxi, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Basic Medical Science, Nanchang University, Nanchang, 330006, Jiangxi, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Tang
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, 330031, Jiangxi, China.
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: College of Basic Medical Science, Nanchang University, Nanchang, 330006, Jiangxi, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Neurology, the first affiliated hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Fang
authors.affiliation: Deparment of Vasculocardiology, the second affiliated hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neurology, Guangdong General hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, Guangzhou, 510080, China. xiong715@126.com.
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, the first affiliated hospital of Nanchang University, Nanchang, 330006, Jiangxi, China. 13767015770@163.com.
authors.forename: Renshi
authors.initials: R
authors.lastname: Xu
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007494:Ireland; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D014481:United States
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins
keywords: DISC1 gene; Nervous system developmental pathway; Sporadic amyotrophic lateral sclerosis