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Linking a genome‐wide association study signal to a LRRK2 coding variant in Parkinson's disease
Author(s) -
Foo Jia Nee,
Chung Sun Ju,
Tan Louis C.,
Liany Herty,
Ryu HoSung,
Hong Myunghee,
Koh Tat Hung,
Irwan Ishak D.,
Au WingLok,
Prakash KumarM.,
Aung Tin,
Cheng ChingYu,
Chong SiowAnn,
Khor Chiea Chuen,
Lee Jimmy,
Tai EShyong,
Vithana Eranga N.,
Wong TienYin,
Song Kyuyoung,
Liu Jianjun,
Tan EngKing
Publication year - 2016
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.26495
Subject(s) - nonsynonymous substitution , linkage disequilibrium , lrrk2 , genetics , genetic association , biology , haplotype , genome wide association study , locus (genetics) , parkinson's disease , allele , disease , gene , genome , single nucleotide polymorphism , medicine , genotype , mutation , pathology
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