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  • Large-scale replication and heterogeneity in Parkinson disease genetic loci

    Author(s)
    Sharma, Manu
    Ioannidis, John PA
    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-Gueell, 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
    Krueger, Rejko
    Griffith University Author(s)
    Mellick, George
    Year published
    2012
    Metadata
    Show full item record
    Abstract
    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 ...
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    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.
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    Journal Title
    Neurology
    Volume
    79
    Issue
    7
    DOI
    https://doi.org/10.1212/WNL.0b013e318264e353
    Subject
    Clinical sciences
    Neurosciences
    Neurology and neuromuscular diseases
    Cognitive and computational psychology
    Publication URI
    http://hdl.handle.net/10072/49833
    Collection
    • Journal articles

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