Aged; Alleles; Case-Control Studies; Female; Gene Frequency; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Male; Middle Aged; Parkinson Disease/genetics; Polymorphism, Single Nucleotide
Abstract :
[en] OBJECTIVE: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. METHODS: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. RESULTS: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78-0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14-1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I(2) estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. CONCLUSION: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
Disciplines :
Genetics & genetic processes
Author, co-author :
Sharma, Manu
Ioannidis, John P. A.
Aasly, Jan O.
Annesi, Grazia
Brice, Alexis
Van Broeckhoven, Christine
Bertram, Lars
Bozi, Maria
Crosiers, David
Clarke, Carl
Facheris, Maurizio
Farrer, Matthew
Garraux, Gaetan
Gispert, Suzana
Auburger, Georg
Vilarino-Guell, Carles
Hadjigeorgiou, Georgios M.
Hicks, Andrew A.
Hattori, Nobutaka
Jeon, Beom
Lesage, Suzanne
Lill, Christina M.
Lin, Juei-Jueng
Lynch, Timothy
Lichtner, Peter
Lang, Anthony E.
Mok, Vincent
Jasinska-Myga, Barbara
Mellick, George D.
Morrison, Karen E.
Opala, Grzegorz
Pramstaller, Peter P.
Pichler, Irene
Park, Sung Sup
Quattrone, Aldo
Rogaeva, Ekaterina
Ross, Owen A.
Stefanis, Leonidas
Stockton, Joanne D.
Satake, Wataru
Silburn, Peter A.
Theuns, Jessie
Tan, Eng-King
Toda, Tatsushi
Tomiyama, Hiroyuki
Uitti, Ryan J.
Wirdefeldt, Karin
Wszolek, Zbigniew
Xiromerisiou, Georgia
Yueh, Kuo-Chu
Zhao, Yi
Gasser, Thomas
Maraganore, Demetrius
KRÜGER, Rejko ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
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