Genome-wide association study of Parkinson's disease in East Asians

Jia Nee Foo, Louis C. Tan, Ishak D. Irwan, Wing Lok Au, Hui Qi Low, Kumar M. Prakash, Azlina Ahmad-Annuar, Jinxin Bei, Anne Y.Y. Chan, Chiung Mei Chen, Yi Chun Chen, Sun Ju Chung, Hao Deng, Shen Yang Lim, Vincent Mok, Hao Pang, Zhong Pei, Rong Peng, Hui Fang Shang, Kyuyoung SongAi Huey Tan, Yih Ru Wu, Tin Aung, Ching Yu Cheng, Fook Tim Chew, Soo Hong Chew, Siow Ann Chong, Richard P. Ebstein, Jimmy Lee, Seang Mei Saw, Adeline Seow, Mythily Subramaniam, E. Shyong Tai, Eranga N. Vithana, Tien Yin Wong, Khai Koon Heng, Wee Yang Meah, Chiea Chuen Khor, Hong Liu, Furen Zhang, Jianjun Liu*, Eng King Tan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

90 Scopus citations

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.

Original languageEnglish
Pages (from-to)226-232
Number of pages7
JournalHuman Molecular Genetics
Volume26
Issue number1
DOIs
StatePublished - 01 01 2017
Externally publishedYes

Bibliographical note

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© 2016 The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

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