Analysis of GWAS-linked loci in Parkinson disease reaffirms PARK16 as a susceptibility locus

被引：87

作者：

Tan, E-K. ^{[1
,2
,3
,4
]}

Kwok, H-K. ^{[6
]}

Tan, L. C. ^{[3
]}

Zhao, W-T. ^{[6
]}

Prakash, K. M. ^{[1
]}

Au, W-L. ^{[3
]}

Pavanni, R. ^{[1
]}

Ng, Y-Y. ^{[1
]}

Satake, W. ^{[5
]}

Zhao, Y. ^{[2
]}

Toda, T. ^{[5
]}

Liu, J-J. ^{[6
]}

机构：

[1] Singapore Gen Hosp, Dept Neurol, Singapore 169108, Singapore

[2] Singapore Gen Hosp, Dept Clin Res, Singapore 169108, Singapore

[3] Natl Inst Neurosci, Singapore, Singapore

[4] Duke NUS Grad Med Sch, Singapore, Singapore

[5] Kobe Univ, Div Neurol Mol Brain Sci, Grad Sch Med, Kobe, Hyogo 657, Japan

[6] ASTAR, Genome Inst Singapore, Singapore 138672, Singapore

来源：

NEUROLOGY | 2010年 / 75卷 / 06期

基金：

日本科学技术振兴机构;

关键词：

GENOME-WIDE ASSOCIATION; COMMON; VARIANTS; MUTATIONS;

D O I：

10.1212/WNL.0b013e3181eccfcd

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

Objective: A genome-wide association study (GWAS) in the Japanese population identified 2 new Parkinson disease (PD) susceptibility loci on 1q32 (PARK16) (OMIM 613164) and BST1. We analyzed single nucleotide polymorphism (SNPs) located at the GWAS-linked loci (PARK16, PARK8, PARK1, and BST1) in a Chinese population and also conducted a meta-analysis in Asians by pooling 2 independent replication studies from Japan. Methods: We conducted an analysis of 13 SNPs associated with PD GWAS-linked loci in 2 case-control cohorts comprised of 1,349 ethnic Chinese subjects. Results: PARK16, PARK8, and PARK1 loci but not BST1 were found to be associated with PD. PARK16 SNPs were associated with a decreased risk while PARK1 and PARK8 SNPs were associated with an increased risk of PD. A pooled analysis of our Chinese cohorts and 2 Japanese replication cohorts involving 1,366 subjects with PD and 16,669 controls revealed robust association with these 3 loci and also BST1. There was a trend toward a stronger protective effect of SNPs at the PARK16 locus in sporadic PD compared to familial cases and in older compared to younger subjects. Conclusions: Our study reaffirms the role of GWAS-linked loci in PD in Asian subjects and the strength of association is similar between Chinese and Japanese subjects. Efforts to elucidate the associated gene within PARK16 locus are warranted. Neurology (R) 2010; 75: 508-512

引用

页码：508 / 512

页数：5

共 17 条

[1]

Common and rare variants in multifactorial susceptibility to common diseases [J].

Bodmer, Walter ;

Bonilla, Carolina .

NATURE GENETICS, 2008, 40 (06) :695-701

[2]

Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson's disease:: a large-scale international study [J].

Elbaz, Alexis ;

Nelson, Lorene M. ;

Payami, Haydeh ;

Ioannidis, John P. A. ;

Fiske, Brian K. ;

Annesi, Grazia ;

Belin, Andrea Carmine ;

Factor, Stewart A. ;

Ferrarese, Carlo ;

Hadjigeorgiou, Georgios M. ;

Higgins, Donald S. ;

Kawakami, Hideshi ;

Krueger, Rejko ;

Marder, Karen S. ;

Mayeux, Richard P. ;

Mellick, George D. ;

Nutt, John G. ;

Ritz, Beate ;

Samii, Ali ;

Tanner, Caroline M. ;

Van Broeckhoven, Christine ;

Van Den Eeden, Stephen K. ;

Wirdefeldt, Karin ;

Zabetian, Cyrus P. ;

Dehem, Marie ;

Montimurro, Jennifer S. ;

Southwick, Audrey ;

Myers, Richard M. ;

Trikalinos, Thomas A. .

LANCET NEUROLOGY, 2006, 5 (11) :917-923

[3]

Non-Replication of Association for Six Polymorphisms From Meta-Analysis of Genome-Wide Association Studies of Parkinson's Disease: Large-Scale Collaborative Study [J].

Evangelou, Evangelos ;

Maraganore, Demetrius M. ;

Annesi, Grazia ;

Brijhina, Laura ;

Brice, Alexis ;

Elbaz, Alexis ;

Ferrarese, Carlo ;

Hadjigeorgiou, Georgios M. ;

Krueger, Rejko ;

Lambert, Jean-Charles ;

Lesage, Suzanne ;

Markopoulou, Katerina ;

Mellick, George D. ;

Meeus, Bram ;

Pedersen, Nancy L. ;

Quattrone, Aldo ;

Van Broeckhoven, Christine ;

Sharma, Manu ;

Silburn, Peter A. ;

Tan, Eng-King ;

Wirdefeldt, Karin ;

Ioannidis, John P. A. .

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2010, 153B (01) :220-228

[4]

Genome-wide genotyping in Parkinson's disease and neurologically normal controls:: first stage analysis and public release of data [J].

Fung, Hon-Chung ;

Scholz, Sonja ;

Matarin, Mar ;

Simon-Sanchez, Javier ;

Hernandez, Dena ;

Britton, Angela ;

Gibbs, J. Raphael ;

Langefeld, Carl ;

Stiegert, Matt L. ;

Schymick, Jennifer ;

Okun, Michael S. ;

Mandel, Ronald J. ;

Fernandez, Hubert H. ;

Foote, Kelly D. ;

Rodriguez, Ramon L. ;

Peckham, Elizabeth ;

De Vrieze, Fabienne Wavrant ;

Gwinn-Hardy, Katrina ;

Hardy, John A. ;

Singleton, Andrew .

LANCET NEUROLOGY, 2006, 5 (11) :911-916

[5]

ACCURACY OF CLINICAL-DIAGNOSIS OF IDIOPATHIC PARKINSONS-DISEASE - A CLINICOPATHOLOGICAL STUDY OF 100 CASES [J].

HUGHES, AJ ;

DANIEL, SE ;

KILFORD, L ;

LEES, AJ .

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1992, 55 (03) :181-184

[6]

Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson disease [J].

Maraganore, Demetrius M. ;

de Andrade, Mariza ;

Elbaz, Alexis ;

Farrer, Matthew J. ;

Ioannidis, John P.A. ;

Krueger, Rejko ;

Rocca, Walter A. ;

Schneider, Nicole K. ;

Lesnick, Timothy G. ;

Lincoln, Sarah J. ;

Hulihan, Mary M. ;

Aasly, Jan O. ;

Ashizawa, Tetsuo ;

Chartier-Harlin, Marie-Christine ;

Checkoway, Harvey ;

Ferrarese, Carlo ;

Hadjigeorgiou, Georgios ;

Hattori, Nobutaka ;

Kawakami, Hideshi ;

Lambert, Jean-Charles ;

Lynch, Timothy ;

Mellick, George D. ;

Papapetropoulos, Spiridon ;

Parsian, Abbas ;

Quattrone, Aldo ;

Riess, Olaf ;

Tan, Eng-King ;

Van Broeckhoven, Christine .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2006, 296 (06) :661-670

[7]

High-resolution whole-genome association study of Parkinson disease [J].

Maraganore, DM ;

de Andrade, M ;

Lesnick, TG ;

Strain, KJ ;

Farrer, MJ ;

Rocca, WA ;

Pant, PVK ;

Frazer, KA ;

Cox, DR ;

Ballinger, DG .

AMERICAN JOURNAL OF HUMAN GENETICS, 2005, 77 (05) :685-693

[8]

Genomewide association study for susceptibility genes contributing to familial Parkinson disease [J].

Pankratz, Nathan ;

Wilk, Jemma B. ;

Latourelle, Jeanne C. ;

DeStefano, Anita L. ;

Halter, Cheryl ;

Pugh, Elizabeth W. ;

Doheny, Kimberly F. ;

Gusella, James F. ;

Nichols, William C. ;

Foroud, Tatiana ;

Myers, Richard H. .

HUMAN GENETICS, 2009, 124 (06) :593-605

[9]

Analysis of Lrrk2 R1628P as a risk factor for Parkinson's disease [J].

Ross, Owen A. ;

Wu, Yih-Ru ;

Lee, Mei-Ching ;

Funayama, Manabu ;

Chen, Meng-Ling ;

Soto, Alexandra I. ;

Mata, Ignacio F. ;

Lee-Chen, Guey-Jen ;

Chen, Chiung Mei ;

Tang, Michelle ;

Zhao, Yi ;

Hattori, Nobutaka ;

Farrer, Matthew J. ;

Tan, Eng-King ;

Wu, Ruey-Meei .

ANNALS OF NEUROLOGY, 2008, 64 (01) :88-92

[10]

Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease [J].

Satake, Wataru ;

Nakabayashi, Yuko ;

Mizuta, Ikuko ;

Hirota, Yushi ;

Ito, Chiyomi ;

Kubo, Michiaki ;

Kawaguchi, Takahisa ;

Tsunoda, Tatsuhiko ;

Watanabe, Masahiko ;

Takeda, Atsushi ;

Tomiyama, Hiroyuki ;

Nakashima, Kenji ;

Hasegawa, Kazuko ;

Obata, Fumiya ;

Yoshikawa, Takeo ;

Kawakami, Hideshi ;

Sakoda, Saburo ;

Yamamoto, Mitsutoshi ;

Hattori, Nobutaka ;

Murata, Miho ;

Nakamura, Yusuke ;

Toda, Tatsushi .

NATURE GENETICS, 2009, 41 (12) :1303-U61

← 1 2 →