title: Genome-wide association study of Parkinson's disease in East Asians.
abstract: Genome-wide association studies (GWAS) on Parkinson's disease (PD) have mostly been done in Europeans and Japanese. No study has been done in Han Chinese, which make up nearly a fifth of the world population. We conducted the first Han Chinese GWAS analysing a total of 22,729 subjects (5,125 PD cases and 17,604 controls) from Singapore, Hong Kong, Malaysia, Korea, mainland China and Taiwan. We performed imputation, merging and logistic regression analyses of 2,402,394 SNPs passing quality control filters in 779 PD cases, 13,227 controls, adjusted for the first three principal components. 90 SNPs with association P < 10-4 were validated in 9 additional sample collections and the results were combined using fixed-effects inverse-variance meta-analysis. We observed strong associations reaching genome-wide significance at SNCA, LRRK2 and MCCC1, confirming their important roles in both European and Asian PD. We also identified significant (P < 0.05) associations at 5 loci (DLG2, SIPA1L2, STK39, VPS13C and RIT2), and observed the same direction of associations at 9 other loci including BST1 and PARK16. Allelic heterogeneity was observed at LRRK2 while European risk SNPs at 6 other loci including MAPT and GBA-SYT11 were non-polymorphic or very rare in our cohort. Overall, we replicate associations at SNCA, LRRK2, MCCC1 and 14 other European PD loci but did not identify Asian-specific loci with large effects (OR > 1.45) on PD risk. Our results also demonstrate some differences in the genetic contribution to PD between Europeans and Asians. Further pan-ethnic meta-analysis with European GWAS cohorts may unravel new PD loci.
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.|Human Genetics, Genome Institute of Singapore, A*STAR, Singapore.
authors.forename: Jia Nee
authors.initials: JN
authors.lastname: Foo
authors.affiliation: Department of Neurology, National Neuroscience Institute, Singapore.
authors.forename: Louis C
authors.initials: LC
authors.lastname: Tan
authors.affiliation: Human Genetics, Genome Institute of Singapore, A*STAR, Singapore.
authors.forename: Ishak D
authors.initials: ID
authors.lastname: Irwan
authors.affiliation: Department of Neurology, National Neuroscience Institute, Singapore.
authors.forename: Wing-Lok
authors.initials: WL
authors.lastname: Au
authors.affiliation: Human Genetics, Genome Institute of Singapore, A*STAR, Singapore.
authors.forename: Hui Qi
authors.initials: HQ
authors.lastname: Low
authors.affiliation: Department of Neurology, National Neuroscience Institute, Singapore.
authors.forename: Kumar-M
authors.initials: KM
authors.lastname: Prakash
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Azlina
authors.initials: A
authors.lastname: Ahmad-Annuar
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Jinxin
authors.initials: J
authors.lastname: Bei
authors.affiliation: Neurology Division, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.
authors.forename: Anne Yy
authors.initials: AY
authors.lastname: Chan
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan, Republic of China.
authors.forename: Chiung Mei
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan, Republic of China.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Sun Ju
authors.initials: SJ
authors.lastname: Chung
authors.affiliation: Department of Neurology and Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Shen-Yang
authors.initials: SY
authors.lastname: Lim
authors.affiliation: Neurology Division, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mok
authors.affiliation: School of Forensic Medicine, China Medical University, Shenyang, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Pang
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Pei
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Peng
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Shang
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Kyuyoung
authors.initials: K
authors.lastname: Song
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Ai Huey
authors.initials: AH
authors.lastname: Tan
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan, Republic of China.
authors.forename: Yih-Ru
authors.initials: YR
authors.lastname: Wu
authors.affiliation: Singapore Eye Research Institute, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.affiliation: Singapore Eye Research Institute, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.|Duke-National University of Singapore Medical School, Singapore.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore.
authors.forename: Fook Tim
authors.initials: FT
authors.lastname: Chew
authors.affiliation: Department of Economics, National University of Singapore, Singapore.
authors.forename: Soo-Hong
authors.initials: SH
authors.lastname: Chew
authors.affiliation: Institute of Mental Health, Singapore.
authors.forename: Siow-Ann
authors.initials: SA
authors.lastname: Chong
authors.affiliation: Department of Psychology, National University of Singapore, Singapore.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Ebstein
authors.affiliation: Duke-National University of Singapore Medical School, Singapore.|Institute of Mental Health, Singapore.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lee
authors.affiliation: Singapore Eye Research Institute, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.|Duke-National University of Singapore Medical School, Singapore.|Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore.
authors.forename: Seang-Mei
authors.initials: SM
authors.lastname: Saw
authors.affiliation: Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore.
authors.forename: Adeline
authors.initials: A
authors.lastname: Seow
authors.affiliation: Institute of Mental Health, Singapore.
authors.forename: Mythily
authors.initials: M
authors.lastname: Subramaniam
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.
authors.forename: E-Shyong
authors.initials: ES
authors.lastname: Tai
authors.affiliation: Singapore Eye Research Institute, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.|Duke-National University of Singapore Medical School, Singapore.
authors.forename: Eranga N
authors.initials: EN
authors.lastname: Vithana
authors.affiliation: Singapore Eye Research Institute, Singapore.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.|Duke-National University of Singapore Medical School, Singapore.
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Human Genetics, Genome Institute of Singapore, A*STAR, Singapore.
authors.forename: Khai Koon
authors.initials: KK
authors.lastname: Heng
authors.affiliation: Human Genetics, Genome Institute of Singapore, A*STAR, Singapore.
authors.forename: Wee-Yang
authors.initials: WY
authors.lastname: Meah
authors.affiliation: Human Genetics, Genome Institute of Singapore, A*STAR, Singapore.|Singapore Eye Research Institute, Singapore.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Science, Jinan, Shandong, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Science, Jinan, Shandong, People's Republic of China.
authors.forename: Furen
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Human Genetics, Genome Institute of Singapore, A*STAR, Singapore.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurology, National Neuroscience Institute, Singapore.|Duke-National University of Singapore Medical School, Singapore.
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism*; D016022:Case-Control Studies; D005006:Ethnicity / Q000235:genetics*; D005202:Asia, Eastern / Q000453:epidemiology; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: D015415:Biomarkers