title: Analysis of non-synonymous-coding variants of Parkinson's disease-related pathogenic and susceptibility genes in East Asian populations.
abstract: To evaluate the contribution of non-synonymous-coding variants of known familial and genome-wide association studies (GWAS)-linked genes for Parkinson's disease (PD) to PD risk in the East Asian population, we sequenced all the coding exons of 39 PD-related disease genes and evaluated the accumulation of rare non-synonymous-coding variants in 375 early-onset PD cases and 399 controls. We also genotyped 782 non-synonymous-coding variants of these genes in 710 late-onset PD cases and 9046 population controls. Significant enrichment of LRRK2 variants was observed in both early- and late-onset PD (odds ratio = 1.58; 95% confidence interval = 1.29-1.93; P = 8.05 × 10(-6)). Moderate enrichment was also observed in FGF20, MCCC1, GBA and ITGA8. Half of the rare variants anticipated to cause loss of function of these genes were present in healthy controls. Overall, non-synonymous-coding variants of known familial and GWAS-linked genes appear to make a limited contribution to PD risk, suggesting that clinical sequencing of these genes will provide limited information for risk prediction and molecular diagnosis.
authors.affiliation: 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: Herty
authors.initials: H
authors.lastname: Liany
authors.affiliation: Human Genetics, Genome Institute of Singapore, A*STAR, Singapore.
authors.forename: Tat Hung
authors.initials: TH
authors.lastname: Koh
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: Yen Yek
authors.initials: YY
authors.lastname: Ng
authors.affiliation: Department of Biomedical Science and.
authors.forename: Azlina
authors.initials: A
authors.lastname: Ahmad-Annuar
authors.affiliation: Department of Neurology, National Neuroscience Institute, Singapore.
authors.forename: Wing-Lok
authors.initials: WL
authors.lastname: Au
authors.affiliation: Singapore Eye Research Institute, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
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 Y Y
authors.initials: AY
authors.lastname: Chan
authors.affiliation: Institute of Mental Health, Singapore.
authors.forename: Siow-Ann
authors.initials: SA
authors.lastname: Chong
authors.affiliation: Department of Neurology, Asan Medical Center and.
authors.forename: Sun Ju
authors.initials: SJ
authors.lastname: Chung
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Yusun
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Human Genetics, Genome Institute of Singapore, A*STAR, Singapore Singapore Eye Research Institute, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Department of Neurology, Asan Medical Center and.
authors.forename: Juyeon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Institute of Mental Health, Singapore Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lee
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: Department of Neurology, National Neuroscience Institute, Singapore.
authors.forename: Kumar-M
authors.initials: KM
authors.lastname: Prakash
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: Duke-National University of Singapore Graduate Medical School, Singapore Department of Medicine, Yong Loo Lin School of Medicine and Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, 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 of Singapore, Singapore Duke-National University of Singapore Graduate 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 of Singapore, Singapore.
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Department of Neurology, National Neuroscience Institute, Singapore Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
authors.affiliation: Human Genetics, Genome Institute of Singapore, A*STAR, Singapore Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore liuj3@gis.a-star.edu.sg.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016366:Open Reading Frames; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*