title: Linking a genome-wide association study signal to a LRRK2 coding variant in Parkinson's disease.
abstract: BACKGROUND
  Genome-wide association studies have identified several loci associated with Parkinson's disease (PD). Whole-exome sequencing detects rare coding variants, but their links with PD genome-wide association study loci are unknown. Our objective was to investigate whether nonsynonymous variants in LRRK2 can explain associations at the PD-associated locus tagged by rs1994090.
  
  
  METHODS
  We sequenced all coding exons of LRRK2 in 453 East Asian samples and evaluated linkage disequilibrium between each nonsynonymous variant and rs1994090. We then tested selected variants and haplotypes for association with PD in 13,581 East Asian samples.
  
  
  RESULTS
  Of all the nonsynonymous variants, only p.Gly2385Arg was in moderate linkage disequilibrium with rs1994090 and was observed on haplotypes tagged by the rs1994090-C risk allele. Conditional analyses showed that associations at these 2 variants are not independent.
  
  
  CONCLUSIONS
  LRRK2 p.Gly2385Arg can explain most if not all of the PD association at rs1994090 in East Asians, but other nonsynonymous variants are independent. © 2015 International Parkinson and Movement Disorder Society.
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, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sun Ju
authors.initials: SJ
authors.lastname: Chung
authors.affiliation: Department of Neurology, Singapore General Hospital, 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: Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Ho-Sung
authors.initials: HS
authors.lastname: Ryu
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Myunghee
authors.initials: M
authors.lastname: Hong
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, Singapore General Hospital, National Neuroscience Institute, Singapore.
authors.forename: Wing-Lok
authors.initials: WL
authors.lastname: Au
authors.affiliation: Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore.
authors.forename: Kumar-M
authors.initials: KM
authors.lastname: Prakash
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: 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: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Institute of Mental Health, Singapore.
authors.forename: Siow-Ann
authors.initials: SA
authors.lastname: Chong
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 of Singapore, Singapore, Singapore.
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Duke-National University of Singapore Graduate Medical School, Singapore.|Institute of Mental Health, Singapore.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.|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.|Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
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: 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.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore.|Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
mesh_terms: D000368:Aged; D005091:Exons / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D056910:Republic of Korea; D012846:Singapore
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: Parkinson's disease; coding variants; genome-wide association; human genetics; sequencing