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

被引：92

作者：

Foo, Jia Nee ^{[1
,2
]}

Tan, Louis C. ^{[3
]}

Irwan, Ishak D. ^{[2
]}

Au, Wing-Lok ^{[3
]}

Low, Hui Qi ^{[2
]}

Prakash, Kumar-M. ^{[3
]}

Ahmad-Annuar, Azlina ^{[4
]}

Bei, Jinxin ^{[5
]}

Chan, Anne Y. Y. ^{[6
]}

Chen, Chiung Mei ^{[7
]}

Chen, Yi-Chun ^{[7
]}

Chung, Sun Ju ^{[8
]}

Deng, Hao ^{[9
,10
]}

Lim, Shen-Yang ^{[11
]}

Mok, Vincent ^{[6
]}

Pang, Hao ^{[12
]}

Pei, Zhong ^{[13
]}

Peng, Rong ^{[14
]}

Shang, Hui-Fang ^{[14
]}

Song, Kyuyoung ^{[15
]}

Tan, Ai Huey ^{[11
]}

Wu, Yih-Ru ^{[7
]}

Aung, Tin ^{[16
,17
]}

Cheng, Ching-Yu ^{[16
,17
,18
]}

Chew, Fook Tim ^{[19
]}

Chew, Soo-Hong ^{[20
]}

Chong, Siow-Ann ^{[21
]}

Ebstein, Richard P. ^{[22
]}

Lee, Jimmy ^{[18
,21
]}

Saw, Seang-Mei ^{[16
,17
,18
,23
]}

Seow, Adeline ^{[23
]}

Subramaniam, Mythily ^{[21
]}

Tai, E-Shyong ^{[24
]}

Vithana, Eranga N. ^{[16
,17
,18
]}

Wong, Tien-Yin ^{[16
,17
,18
]}

Heng, Khai Koon ^{[2
]}

Meah, Wee-Yang ^{[2
]}

Khor, Chiea Chuen ^{[2
,16
,25
]}

Liu, Hong ^{[26
]}

Zhang, Furen ^{[26
]}

Liu, Jianjun ^{[2
]}

Tan, Eng-King ^{[3
,18
]}

机构：

[1] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore

[2] ASTAR, Genome Inst Singapore, Human Genet, 60 Biopolis St,Genome 02-01, Singapore 138672, Singapore

[3] Natl Neurosci Inst, Dept Neurol, Singapore, Singapore

[4] Univ Malaya, Fac Med, Dept Biomed Sci, Kuala Lumpur, Malaysia

[5] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China

[6] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Neurol Div, Hong Kong, Hong Kong, Peoples R China

[7] Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan

[8] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul, South Korea

[9] Cent South Univ, Xiangya Hosp 3, Dept Neurol, Changsha, Hunan, Peoples R China

[10] Cent South Univ, Xiangya Hosp 3, Ctr Med Expt, Changsha, Hunan, Peoples R China

[11] Univ Malaya, Med, Fac Med, Kuala Lumpur, Malaysia

[12] China Med Univ, Sch Forens Med, Shenyang, Peoples R China

[13] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Neurol, Guangzhou, Guangdong, Peoples R China

[14] Sichuan Univ, West China Hosp, Dept Neurol, Chengdu, Sichuan, Peoples R China

[15] Univ Ulsan, Coll Med, Dept Biochem & Mol Biol, Seoul, South Korea

[16] Singapore Eye Res Inst, Singapore, Singapore

[17] Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore

[18] Duke Natl Univ Singapore, Sch Med, Singapore, Singapore

[19] Natl Univ Singapore, Dept Biol Sci, Singapore, Singapore

[20] Natl Univ Singapore, Dept Econ, Singapore, Singapore

[21] Inst Mental Hlth, Singapore, Singapore

[22] Natl Univ Singapore, Dept Psychol, Singapore, Singapore

[23] Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore

[24] Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore

[25] Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Biochem, Singapore, Singapore

[26] Shandong Acad Med Sci, Shandong Prov Inst Dermatol & Venereol, Jinan, Shandong, Peoples R China

来源：

HUMAN MOLECULAR GENETICS | 2017年 / 26卷 / 01期

基金：

英国医学研究理事会; 新加坡国家研究基金会;

关键词：

GENOTYPE IMPUTATION; IDENTIFICATION; METAANALYSIS; VARIANTS; LINKAGE; LOCI; SET;

D O I：

10.1093/hmg/ddw379

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：226 / 232

页数：7

共 21 条

[1] A global reference for human genetic variation
Altshuler, David M.
Durbin, Richard M.
Abecasis, Goncalo R.
Bentley, David R.
Chakravarti, Aravinda
Clark, Andrew G.
Donnelly, Peter
Eichler, Evan E.
Flicek, Paul
Gabriel, Stacey B.
Gibbs, Richard A.
Green, Eric D.
Hurles, Matthew E.
Knoppers, Bartha M.
Korbel, Jan O.
Lander, Eric S.
Lee, Charles
Lehrach, Hans
Mardis, Elaine R.
Marth, Gabor T.
McVean, Gil A.
Nickerson, Deborah A.
Wang, Jun
Wilson, Richard K.
Boerwinkle, Eric
Doddapaneni, Harsha
Han, Yi
Korchina, Viktoriya
Kovar, Christie
Lee, Sandra
Muzny, Donna
Reid, Jeffrey G.
Zhu, Yiming
Chang, Yuqi
Feng, Qiang
Fang, Xiaodong
Guo, Xiaosen
Jian, Min
Jiang, Hui
Jin, Xin
Lan, Tianming
Li, Guoqing
Li, Jingxiang
Li, Yingrui
Liu, Shengmao
Liu, Xiao
Lu, Yao
Ma, Xuedi
Tang, Meifang
Wang, Bo
[J]. NATURE, 2015, 526 (7571) : 68 - +
[2] Genetic Structure of the Han Chinese Population Revealed by Genome-wide SNP Variation
Chen, Jieming
Zheng, Houfeng
Bei, Jin-Xin
Sun, Liangdan
Jia, Wei-hua
Li, Tao
Zhang, Furen
Seielstad, Mark
Zeng, Yi-Xin
Zhang, Xuejun
Liu, Jianjun
[J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 85 (06) : 775 - 785
[3] Delaneau O, 2012, NAT METHODS, V9, P179, DOI [10.1038/NMETH.1785, 10.1038/nmeth.1785]
[4] Web-Based Genome-Wide Association Study Identifies Two Novel Loci and a Substantial Genetic Component for Parkinson's Disease
Do, Chuong B.
Tung, Joyce Y.
Dorfman, Elizabeth
Kiefer, Amy K.
Drabant, Emily M.
Francke, Uta
Mountain, Joanna L.
Goldman, Samuel M.
Tanner, Caroline M.
Langston, J. William
Wojcicki, Anne
Eriksson, Nicholas
[J]. PLOS GENETICS, 2011, 7 (06):
[5] Linking a genome-wide association study signal to a LRRK2 coding variant in Parkinson's disease
Foo, Jia Nee
Chung, Sun Ju
Tan, Louis C.
Liany, Herty
Ryu, Ho-Sung
Hong, Myunghee
Koh, Tat Hung
Irwan, Ishak D.
Au, Wing-Lok
Prakash, Kumar-M.
Aung, Tin
Cheng, Ching-Yu
Chong, Siow-Ann
Khor, Chiea Chuen
Lee, Jimmy
Tai, E-Shyong
Vithana, Eranga N.
Wong, Tien-Yin
Song, Kyuyoung
Liu, Jianjun
Tan, Eng-King
[J]. MOVEMENT DISORDERS, 2016, 31 (04) : 484 - 487
[6] Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease
Hamza, Taye H.
Zabetian, Cyrus P.
Tenesa, Albert
Laederach, Alain
Montimurro, Jennifer
Yearout, Dora
Kay, Denise M.
Doheny, Kimberly F.
Paschall, Justin
Pugh, Elizabeth
Kusel, Victoria I.
Collura, Randall
Roberts, John
Griffith, Alida
Samii, Ali
Scott, William K.
Nutt, John
Factor, Stewart A.
Payami, Haydeh
[J]. NATURE GENETICS, 2010, 42 (09) : 781 - U75
[7] Fast and accurate genotype imputation in genome-wide association studies through pre-phasing
Howie, Bryan
Fuchsberger, Christian
Stephens, Matthew
Marchini, Jonathan
Abecasis, Goncalo R.
[J]. NATURE GENETICS, 2012, 44 (08) : 955 - +
[8] Genotype Imputation with Thousands of Genomes
Howie, Bryan
Marchini, Jonathan
Stephens, Matthew
[J]. G3-GENES GENOMES GENETICS, 2011, 1 (06): : 457 - 469
[9] A Flexible and Accurate Genotype Imputation Method for the Next Generation of Genome-Wide Association Studies
Howie, Bryan N.
Donnelly, Peter
Marchini, Jonathan
[J]. PLOS GENETICS, 2009, 5 (06)
[10] Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database
Lill, Christina M.
Roehr, Johannes T.
McQueen, Matthew B.
Kavvoura, Fotini K.
Bagade, Sachin
Schjeide, Brit-Maren M.
Schjeide, Leif M.
Meissner, Esther
Zauft, Ute
Allen, Nicole C.
Liu, Tian
Schilling, Marcel
Anderson, Kari J.
Beecham, Gary
Berg, Daniela
Biernacka, Joanna M.
Brice, Alexis
DeStefano, Anita L.
Do, Chuong B.
Eriksson, Nicholas
Factor, Stewart A.
Farrer, Matthew J.
Foroud, Tatiana
Gasser, Thomas
Hamza, Taye
Hardy, John A.
Heutink, Peter
Hill-Burns, Erin M.
Klein, Christine
Latourelle, Jeanne C.
Maraganore, Demetrius M.
Martin, Eden R.
Martinez, Maria
Myers, Richard H.
Nalls, Michael A.
Pankratz, Nathan
Payami, Haydeh
Satake, Wataru
Scott, William K.
Sharma, Manu
Singleton, Andrew B.
Stefansson, Kari
Toda, Tatsushi
Tung, Joyce Y.
Vance, Jeffery
Wood, Nick W.
Zabetian, Cyrus P.
Young, Peter
Tanzi, Rudolph E.
Khoury, Muin J.
[J]. PLOS GENETICS, 2012, 8 (03):

← 1 2 3 →