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

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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.

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Acknowledgments

We are grateful to the PD patients who generously contributed their time and materials for this research.

Conflict of Interest

The authors declare no conflict of interest.

Funding

This work was funded by the committee of the Chinese National Nature Science (grant number 30560042, 81160161, 81360198, 30871384), the education department of Jiangxi province (grant number [2005(183)], GJJ10303), and Guangdong Provincial Science & Technology Project Foundation (grant number 2012B031800410).

Author Contributions

Xu R, Deng L, and Zhang X conceived and designed the experiments. Hu Y, Zhang J, Deng L, Mei P, Wei Y, and Fang X performed the experiments. Xu R, Hu Y, Lin J, and Deng L analyzed the data. Cao X and Zhang X contributed partial materials. Xu R and Deng L wrote the paper. Hu Y, Deng L, and Zhang J are co-first authors. Xu R and Zhang X are the cooperation corresponding authors; these authors contributed to the research work of the same.

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China

    Yakun Hu, Xin Fang & Renshi Xu

  2. Institute of Translational Medicine, Nanchang University, Nanchang, 330006, Jiangxi, China

    Libing Deng, Puming Mei, Jiari Lin & Yi Wei

  3. Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Nanchang University, Nanchang, 330006, Jiangxi, China

    Jie Zhang

  4. Department of Neurology, The Affiliated Union Hospital of Huazhong Technological University, Wuhan, 430006, Hubei, China

    Xuebing Cao

  5. Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, Guangzhou, 510080, Guangdong, China

    Xiong Zhang

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  1. Yakun Hu
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Hu, Y., Deng, L., Zhang, J. et al. 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 53, 4302–4318 (2016). https://doi.org/10.1007/s12035-015-9331-y

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