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Sharma, M.L.* ; Ioannidis, J.P.A.* ; Aasly, J.O.* ; Annesi, G.* ; Brice, A.* ; van Broeckhoven, C.L.* ; Bertram, L.* ; Bozi, M.* ; Crosiers, D.* ; Clarke, C.E.* ; Facheris, M.F.* ; Farrer, M.J.* ; Garraux, G.* ; Gispert, S.* ; Auburger, G.W.J.* ; Vilariño-Güell, C.* ; Hadjigeorgiou, G.M.* ; Hicks, A.A.* ; Hattori, N.* ; Jeon, B.* ; Lesage, S.R.* ; Lill, C.M.* ; Lin, J.* ; Lynch, T.M.* ; Lichtner, P.K. ; Lang, A.* ; Mok, V.* ; Jasinska-Myga, B.* ; Mellick, G.D.* ; Morrison, K.E.* ; Opala, G.M.* ; Pramstaller, P.P.* ; Pichler, I.* ; Park, S.H.* ; Quattrone, A.* ; Rogaeva, E.A.* ; Ross, O.A.* ; Stefanis, L.* ; Stockton, J.D.* ; Satake, W.* ; Silburn, P.A.S.* ; Theuns, J.* ; Tan, E.K.* ; Toda, T.* ; Tomiyama, H.* ; Uitti, R.J.* ; Wirdefeldt, K.* ; Wszołek, Z.K.* ; Xiromerisiou, G.* ; Yueh, K.C.* ; Zhao, Y.* ; Gasser, T.H.* ; Maraganore, D.M.* ; Kruger, R.*

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

Neurology 79, 659-667 (2012)
Publ. Version/Full Text DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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 (I2 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. Copyright © 2012 by AAN Enterprises, Inc.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY GENES; COMPLEX DISEASES; METAANALYSES; VARIANTS; SNCA; MAPT; UNCERTAINTY; RISK
ISSN (print) / ISBN 0028-3878
e-ISSN 1526-632X
Journal Neurology
Quellenangaben Volume: 79, Issue: 7, Pages: 659-667 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)