A Pooling Genome-Wide Association Study Combining a Pathway Analysis for Typical Sporadic Parkinson's Disease in the Han Population of Chinese Mainland

Mol Neurobiol. 2016 Sep;53(7):4302-18. doi: 10.1007/s12035-015-9331-y. Epub 2015 Jul 31.

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.

Keywords: Candidate genes; Chinese Han population; Genome-wide association study; Pathway; Sporadic Parkinson’s disease.

MeSH terms

  • Asian People / genetics*
  • Axons / metabolism
  • Chromosomes, Human, Pair 8 / genetics
  • Ethnicity / genetics*
  • Gene Frequency / genetics
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Humans
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Signal Transduction / genetics*