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Large-scale replication and heterogeneity in Parkinson disease genetic loci.
Neurology. 2012 Aug 14; 79(7):659-67.Neur

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.

Authors+Show Affiliations

Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. manu.sharma@uni-tuebingen.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22786590

Citation

Sharma, Manu, et al. "Large-scale Replication and Heterogeneity in Parkinson Disease Genetic Loci." Neurology, vol. 79, no. 7, 2012, pp. 659-67.
Sharma M, Ioannidis JP, Aasly JO, et al. Large-scale replication and heterogeneity in Parkinson disease genetic loci. Neurology. 2012;79(7):659-67.
Sharma, M., Ioannidis, J. P., Aasly, J. O., Annesi, G., Brice, A., Van Broeckhoven, C., Bertram, L., Bozi, M., Crosiers, D., Clarke, C., Facheris, M., Farrer, M., Garraux, G., Gispert, S., Auburger, G., Vilariño-Güell, C., Hadjigeorgiou, G. M., Hicks, A. A., Hattori, N., ... Krüger, R. (2012). Large-scale replication and heterogeneity in Parkinson disease genetic loci. Neurology, 79(7), 659-67. https://doi.org/10.1212/WNL.0b013e318264e353
Sharma M, et al. Large-scale Replication and Heterogeneity in Parkinson Disease Genetic Loci. Neurology. 2012 Aug 14;79(7):659-67. PubMed PMID: 22786590.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Large-scale replication and heterogeneity in Parkinson disease genetic loci. AU - Sharma,Manu, AU - Ioannidis,John P A, AU - Aasly,Jan O, AU - Annesi,Grazia, AU - Brice,Alexis, AU - Van Broeckhoven,Christine, AU - Bertram,Lars, AU - Bozi,Maria, AU - Crosiers,David, AU - Clarke,Carl, AU - Facheris,Maurizio, AU - Farrer,Matthew, AU - Garraux,Gaetan, AU - Gispert,Suzana, AU - Auburger,Georg, AU - Vilariño-Güell,Carles, AU - Hadjigeorgiou,Georgios M, AU - Hicks,Andrew A, AU - Hattori,Nobutaka, AU - Jeon,Beom, AU - Lesage,Suzanne, AU - Lill,Christina M, AU - Lin,Juei-Jueng, AU - Lynch,Timothy, AU - Lichtner,Peter, AU - Lang,Anthony E, AU - Mok,Vincent, AU - Jasinska-Myga,Barbara, AU - Mellick,George D, AU - Morrison,Karen E, AU - Opala,Grzegorz, AU - Pramstaller,Peter P, AU - Pichler,Irene, AU - Park,Sung Sup, AU - Quattrone,Aldo, AU - Rogaeva,Ekaterina, AU - Ross,Owen A, AU - Stefanis,Leonidas, AU - Stockton,Joanne D, AU - Satake,Wataru, AU - Silburn,Peter A, AU - Theuns,Jessie, AU - Tan,Eng-King, AU - Toda,Tatsushi, AU - Tomiyama,Hiroyuki, AU - Uitti,Ryan J, AU - Wirdefeldt,Karin, AU - Wszolek,Zbigniew, AU - Xiromerisiou,Georgia, AU - Yueh,Kuo-Chu, AU - Zhao,Yi, AU - Gasser,Thomas, AU - Maraganore,Demetrius, AU - Krüger,Rejko, AU - ,, Y1 - 2012/07/11/ PY - 2012/7/13/entrez PY - 2012/7/13/pubmed PY - 2012/10/25/medline SP - 659 EP - 67 JF - Neurology JO - Neurology VL - 79 IS - 7 N2 - 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. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/22786590/Large_scale_replication_and_heterogeneity_in_Parkinson_disease_genetic_loci_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=22786590 DB - PRIME DP - Unbound Medicine ER -