title: Polygenic determinants of Parkinson's disease in a Chinese population.
abstract: It has been reported that some single-nucleotide polymorphisms (SNPs) are associated with the risk of Parkinson's disease (PD), but whether a combination of these SNPs would have a stronger association with PD than any individual SNP is unknown. Sixteen SNPs located in the 8 genes and/or loci (SNCA, LRRK2, MAPT, GBA, HLA-DR, BST1, PARK16, and PARK17) were analyzed in a Chinese cohort consisting of 1061 well-characterized PD patients and 1066 control subjects from Central South of Mainland China. We found that Rep1, rs356165, and rs11931074 in SNCA gene; G2385R in LRRK2 gene; rs4698412 in BST1 gene; rs1564282 in PARK17; and L444P in GBA gene were associated with PD with adjustment of sex and age (p < 0.05) in the analysis of 16 variants. PD risk increased when Rep1 and rs11931074, G2385R, rs1564282, rs4698412; rs11931074 and G2385R, rs1564282, rs4698412; G2385R and rs1564282, rs4698412; and rs1564282 and rs4698412 were combined for the association analysis. In addition, PD risk increased cumulatively with the increasing number of variants (odds ratio for carrying 3 variants, 3.494). In summary, we confirmed that Rep1, rs356165, and rs11931074 in SNCA gene, G2385R in LRRK2 gene, rs4698412 in BST1 gene, rs1564282 in PARK17, and L444P in GBA gene have an independent and combined significant association with PD. SNPs in these 4 genes have a cumulative effect with PD.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China; State Key Laboratory of Medical Genetics, Changsha, Hunan, People's Republic of China; Human Key Laboratory of Neurodegenerative Disorders, Central South University, Changsha, Hunan, People's Republic of China; Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Guo
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Ri-Li
authors.initials: RL
authors.lastname: Yu
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Qi-Yin
authors.initials: QY
authors.lastname: Sun
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Ling-Yan
authors.initials: LY
authors.lastname: Yao
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Ya-Cen
authors.initials: YC
authors.lastname: Hu
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Zhan-Yun
authors.initials: ZY
authors.lastname: Lv
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Lin-Zi
authors.initials: LZ
authors.lastname: Luo
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China; State Key Laboratory of Medical Genetics, Changsha, Hunan, People's Republic of China; Human Key Laboratory of Neurodegenerative Disorders, Central South University, Changsha, Hunan, People's Republic of China; Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China; State Key Laboratory of Medical Genetics, Changsha, Hunan, People's Republic of China; Human Key Laboratory of Neurodegenerative Disorders, Central South University, Changsha, Hunan, People's Republic of China; Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China; Human Key Laboratory of Neurodegenerative Disorders, Central South University, Changsha, Hunan, People's Republic of China; Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Xin-Xiang
authors.initials: XX
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Medical Genetics, Changsha, Hunan, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Medical Genetics, Changsha, Hunan, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China; State Key Laboratory of Medical Genetics, Changsha, Hunan, People's Republic of China; Human Key Laboratory of Neurodegenerative Disorders, Central South University, Changsha, Hunan, People's Republic of China; Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan, People's Republic of China. Electronic address: bstang7398@163.com.
authors.forename: Bei-Sha
authors.initials: BS
authors.lastname: Tang
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D055815:Young Adult; D051844:alpha-Synuclein / Q000235:genetics
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; C497604:SNCA protein, human; D051844:alpha-Synuclein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D036541:ADP-ribosyl Cyclase; C087521:ADP-ribosyl cyclase 2
keywords: Association analysis; Gene polymorphism; Parkinson's disease