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  Large-scale replication and heterogeneity in Parkinson disease genetic loci

Sharma, M., Ioannidis, J. P., Aasly, J. O., Annesi, G., Brice, A., Van Broeckhoven, C., et al. (2012). Large-scale replication and heterogeneity in Parkinson disease genetic loci. Neurology, 79(7), 659-667. doi:10.1212/WNL.0b013e318264e353.

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Sharma, M., Author
Ioannidis, J. P., Author
Aasly, J. O., Author
Annesi, G., Author
Brice, A., Author
Van Broeckhoven, C., Author
Bertram, L.1, Author           
Bozi, M., Author
Crosiers, D., Author
Clarke, C., Author
Facheris, M., Author
Farrer, M., Author
Garraux, G., Author
Gispert, S., Author
Auburger, G., Author
Vilarino-Guell, C., Author
Hadjigeorgiou, G. M., Author
Hicks, A. A., Author
Hattori, N., Author
Jeon, B., Author
Lesage, S., AuthorLill, C. M.1, Author           Lin, J. J., AuthorLynch, T., AuthorLichtner, P., AuthorLang, A. E., AuthorMok, V., AuthorJasinska-Myga, B., AuthorMellick, G. D., AuthorMorrison, K. E., AuthorOpala, G., AuthorPramstaller, P. P., AuthorPichler, I., AuthorPark, S. S., AuthorQuattrone, A., AuthorRogaeva, E., AuthorRoss, O. A., AuthorStefanis, L., AuthorStockton, J. D., AuthorSatake, W., AuthorSilburn, P. A., AuthorTheuns, J., AuthorTan, E. K., AuthorToda, T., AuthorTomiyama, H., AuthorUitti, R. J., AuthorWirdefeldt, K., AuthorWszolek, Z., AuthorXiromerisiou, G., AuthorYueh, K. C., AuthorZhao, Y., AuthorGasser, T., AuthorMaraganore, D., AuthorKrüger, R., Author more..
Affiliations:
1Neuropsychiatric Genetics (Lars Bertram), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479655              

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Free keywords: 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: 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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Language(s): eng - English
 Dates: 2012-07-112012-08-14
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1212/WNL.0b013e318264e353
 Degree: -

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Title: Neurology
Source Genre: Journal
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Publ. Info: Hagerstown, MD : Lippincott Williams & Wilkins
Pages: - Volume / Issue: 79 (7) Sequence Number: - Start / End Page: 659 - 667 Identifier: ISSN: 0028-3878
CoNE: https://pure.mpg.de/cone/journals/resource/954925246073