title: A Pooling Genome-Wide Association Study Combining a Pathway Analysis for Typical Sporadic Parkinson's Disease in the Han Population of Chinese Mainland.
abstract: Genome-wide association studies (GWAS) on sporadic Parkinson's disease (sPD) are mainly conducted in European and American populations at present, and the Han populations of Chinese mainland (HPCM) almost have not been studied yet. Here, we conducted a pooling GWAS combining a pathway analysis with 862,198 autosomal single nucleotide polymorphisms of IlluminaHumanOmniZhongHua-8 in 250 sPD and 250 controls from HPCM precluded toxicant exposure, age, and heavy coffee drinking habit interference. We revealed that among the 22 potential loci implicated, PRDM2/KIAA1026 (kgp8090149), TSG1/MANEA (kgp154172), PDE10A (kgp8130520), MDGA2 (rs9323124), ATPBD4/LOC100288892 (kgp11333367), ZFP64/TSHZ2 (kgp4156164), PAQR3/ARD1B (kgp9482779), FLJ23172/FNDC3B (kgp760898), C18orf1 (kgp348599), FLJ43860/NCRNA00051 (kgp4105983), CYP1B1/C2orf58 (kgp11353523), WNT9A/LOC728728 (rs849898), ANXA1/LOC100130911 (rs10746953), FLJ35379/LOC100132423 (kgp9550589), PLEKHN1 (kgp7172368), DMRT2/SMARCA2 (kgp10769919), ZNF396/INO80C (rs1362858), C3orf67/LOC339902 (rs6783485), LOC285194/IGSF11 (rs1879553), FGF10/MRPS30 (rs13153459), BARX1/PTPDC1 (kgp6542803), and COL5 A2 (rs11186), the peak significance was at the kgp4105983 of FLJ43860 gene in chromosome 8, the first top strongest associated locus with sPD was PRDM2 (kgp8090149) in chromosome 1, and the 24 pathways including 100 significantly associated genes were strongly associated with sPD from HPCM. The 40 genes were shared by at least two pathways. The most possible associated pathways with sPD were axon guidance, ECM-receptor interaction, neuroactive ligand-receptor interaction, tight junction, focal adhesion, gap junction, long-term depression, drug metabolism-cytochrome P450, adherens junction, endocytosis, and protein digestion and absorption. Our results indicated that these loci, pathways, and their related genes might be involved in the pathogenesis of sPD from HPCM and provided some novel evidences for further searching the genetic pathogenesis of sPD.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
authors.forename: Yakun
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, 330006, Jiangxi, China.
authors.forename: Libing
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Nanchang University, Nanchang, 330006, Jiangxi, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
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: Institute of Translational Medicine, Nanchang University, Nanchang, 330006, Jiangxi, China.
authors.forename: Puming
authors.initials: P
authors.lastname: Mei
authors.affiliation: Department of Neurology, The Affiliated Union Hospital of Huazhong Technological University, Wuhan, 430006, Hubei, China.
authors.forename: Xuebing
authors.initials: X
authors.lastname: Cao
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, 330006, Jiangxi, China.
authors.forename: Jiari
authors.initials: J
authors.lastname: Lin
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, 330006, Jiangxi, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, Guangzhou, 510080, Guangdong, 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: D044466:Asian People / Q000235:genetics*; D001369:Axons / Q000378:metabolism; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*
keywords: Candidate genes; Chinese Han population; Genome-wide association study; Pathway; Sporadic Parkinson’s disease