@article{3111046,
    title = "Large-scale replication and heterogeneity in Parkinson disease genetic loci",
    author = "Sharma, M. and Ioannidis, J.P.A. and Aasly, J.O. and Annesi, G. and Brice, A. and Van Broeckhoven, C. and Bertram, L. and Bozi, M. and Crosiers, D. and Clarke, C. and Facheris, M. and Farrer, M. and Garraux, G. and Gispert, S. and Auburger, G. and Vilariño-Güell, C. and Hadjigeorgiou, G.M. and Hicks, A.A. and Hattori, N. and Jeon, B. and Lesage, S. and Lill, C.M. and Lin, J.-J. and Lynch, T. and Lichtner, P. and Lang, A.E. and Mok, V. and Jasinska-Myga, B. and Mellick, G.D. and Morrison, K.E. and Opala, G. and Pramstaller, P.P. and Pichler, I. and Park, S.S. and Quattrone, A. and Rogaeva, E. and Ross, O.A. and Stefanis, L. and Stockton, J.D. and Satake, W. and Silburn, P.A. and Theuns, J. and Tan, E.-K. and Toda, T. and Tomiyama, H. and Uitti, R.J. and Wirdefeldt, K. and Wszolek, Z. and Xiromerisiou, G. and Yueh, K.-C. and Zhao, Y. and Gasser, T. and Maraganore, D. and Krüger, R.",
    journal = "Functional Neurology",
    year = "2012",
    volume = "79",
    number = "7",
    pages = "659-667",
    publisher = "Lippincott Williams and Wilkins",
    doi = "10.1212/WNL.0b013e318264e353",
    keywords = "ACMSD protein;  alpha synuclein;  BST1 protein;  dendritic cell lysosome associated membrane protein;  GAK1 protein;  HIP1R protein;  HLA DRB5 antigen;  leucine rich repeat kinase 2;  peptides and proteins;  STK39 protein;  SYT11 protein;  tau protein;  unclassified drug, article;  Asian;  Caucasian;  controlled study;  gene frequency;  gene locus;  gene replication;  genetic association;  genetic heterogeneity;  genetic risk;  genetic susceptibility;  genetic variability;  genotyping technique;  human;  major clinical study;  Parkinson disease;  population genetics;  priority journal;  risk assessment;  single nucleotide polymorphism",
    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 (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."
}