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

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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.

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Author and article information

Journal

Journal ID (iso-abbrev): Hum. Mol. Genet.

Title: Human molecular genetics

Publisher: Oxford University Press (OUP)

ISSN (Electronic): 1460-2083

ISSN (Print): 0964-6906

Publication date (Electronic): Jan 01 2017

Volume: 26

Issue: 1

Affiliations

[1 ] Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.

[2 ] Human Genetics, Genome Institute of Singapore, A*STAR, Singapore.

[3 ] Department of Neurology, National Neuroscience Institute, Singapore.

[4 ] Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

[5 ] Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People's Republic of China.

[6 ] 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.

[7 ] Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan, Republic of China.

[8 ] Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

[9 ] Department of Neurology and Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, People's Republic of China.

[10 ] Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

[11 ] School of Forensic Medicine, China Medical University, Shenyang, People's Republic of China.

[12 ] Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.

[13 ] Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

[14 ] Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.

[15 ] Singapore Eye Research Institute, Singapore.

[16 ] Department of Ophthalmology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.

[17 ] Duke-National University of Singapore Medical School, Singapore.

[18 ] Department of Biological Sciences, National University of Singapore, Singapore.

[19 ] Department of Economics, National University of Singapore, Singapore.

[20 ] Institute of Mental Health, Singapore.

[21 ] Department of Psychology, National University of Singapore, Singapore.

[22 ] Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore.

[23 ] Department of Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.

[24 ] Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.

[25 ] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Science, Jinan, Shandong, People's Republic of China.

Article

Publisher Item ID: ddw379

DOI: 10.1093/hmg/ddw379

PubMed ID: 28011712

SO-VID: 6cf8f841-a22b-4577-a365-2785ea4ad507

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