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dc.contributor.authorSharma, Manu
dc.contributor.authorIoannidis, John PA
dc.contributor.authorAasly, Jan O
dc.contributor.authorAnnesi, Grazia
dc.contributor.authorBrice, Alexis
dc.contributor.authorVan Broeckhoven, Christine
dc.contributor.authorBertram, Lars
dc.contributor.authorBozi, Maria
dc.contributor.authorCrosiers, David
dc.contributor.authorClarke, Carl
dc.contributor.authorFacheris, Maurizio
dc.contributor.authorFarrer, Matthew
dc.contributor.authorGarraux, Gaetan
dc.contributor.authorGispert, Suzana
dc.contributor.authorAuburger, Georg
dc.contributor.authorVilarino-Gueell, Carles
dc.contributor.authorHadjigeorgiou, Georgios M
dc.contributor.authorHicks, Andrew A
dc.contributor.authorHattori, Nobutaka
dc.contributor.authorJeon, Beom
dc.contributor.authorLesage, Suzanne
dc.contributor.authorLill, Christina M
dc.contributor.authorLin, Juei-Jueng
dc.contributor.authorLynch, Timothy
dc.contributor.authorLichtner, Peter
dc.contributor.authorLang, Anthony E
dc.contributor.authorMok, Vincent
dc.contributor.authorJasinska-Myga, Barbara
dc.contributor.authorMellick, George D
dc.contributor.authorMorrison, Karen E
dc.contributor.authorOpala, Grzegorz
dc.contributor.authorPramstaller, Peter P
dc.contributor.authorPichler, Irene
dc.contributor.authorPark, Sung Sup
dc.contributor.authorQuattrone, Aldo
dc.contributor.authorRogaeva, Ekaterina
dc.contributor.authorRoss, Owen A
dc.contributor.authorStefanis, Leonidas
dc.contributor.authorStockton, Joanne D
dc.contributor.authorSatake, Wataru
dc.contributor.authorSilburn, Peter A
dc.contributor.authorTheuns, Jessie
dc.contributor.authorTan, Eng-King
dc.contributor.authorToda, Tatsushi
dc.contributor.authorTomiyama, Hiroyuki
dc.contributor.authorUitti, Ryan J
dc.contributor.authorWirdefeldt, Karin
dc.contributor.authorWszolek, Zbigniew
dc.contributor.authorXiromerisiou, Georgia
dc.contributor.authorYueh, Kuo-Chu
dc.contributor.authorZhao, Yi
dc.contributor.authorGasser, Thomas
dc.contributor.authorMaraganore, Demetrius
dc.contributor.authorKrueger, Rejko
dc.date.accessioned2017-05-03T14:10:43Z
dc.date.available2017-05-03T14:10:43Z
dc.date.issued2012
dc.identifier.issn0028-3878
dc.identifier.doi10.1212/WNL.0b013e318264e353
dc.identifier.urihttp://hdl.handle.net/10072/49833
dc.description.abstractOBJECTIVE: 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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherLippincott Williams & Wilkins
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom659
dc.relation.ispartofpageto667
dc.relation.ispartofissue7
dc.relation.ispartofjournalNeurology
dc.relation.ispartofvolume79
dc.rights.retentionY
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchNeurosciences
dc.subject.fieldofresearchNeurology and neuromuscular diseases
dc.subject.fieldofresearchCognitive and computational psychology
dc.subject.fieldofresearchcode3202
dc.subject.fieldofresearchcode3209
dc.subject.fieldofresearchcode320905
dc.subject.fieldofresearchcode5204
dc.titleLarge-scale replication and heterogeneity in Parkinson disease genetic loci
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2014-10-10T01:00:31Z
gro.hasfulltextNo Full Text
gro.griffith.authorMellick, George


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