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  • Sharma, ManuUniversity of Tübingen (author)

Large-scale replication and heterogeneity in Parkinson disease genetic loci

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • 2012
  • 9 s.

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:29175224-3e2e-4dd3-a666-43c8f0174d63
  • https://lup.lub.lu.se/record/29175224-3e2e-4dd3-a666-43c8f0174d63URI
  • https://doi.org/10.1212/WNL.0b013e318264e353DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:125101374URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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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  • Ioannidis, John P AGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Aasly, Jan O.Stanford University (author)
  • Annesi, GraziaSt. Olav’s University Hospital (author)
  • Brice, AlexisNational Institute for Health and Medical Research, France (author)
  • Van Broeckhoven, ChristineUniversity of Antwerp (author)
  • Bertram, LarsUniversity of Antwerp (author)
  • Bozi, MariaNational and Kapodistrian University of Athens (author)
  • Crosiers, DavidNational and Kapodistrian University of Athens (author)
  • Clarke, Carl EAntwerp University Hospital (author)
  • Facheris, Maurizio (author)
  • Farrer, Matthew (author)
  • Garraux, Gaetan (author)
  • Gispert, Suzana (author)
  • Auburger, Georg (author)
  • Vilariño-Güell, Carles (author)
  • Hadjigeorgiou, Georgios M. (author)
  • Hicks, Andrew A (author)
  • Hattori, Nobutaka (author)
  • Jeon, Beom S. (author)
  • Lesage, Suzanne (author)
  • Lill, Christina M. (author)
  • Lin, Juei-Jueng (author)
  • Lynch, Timothy (author)
  • Lichtner, Peter (author)
  • Lang, Anthony E (author)
  • Mok, Vincent (author)
  • Jasinska-Myga, Barbara (author)
  • Mellick, George D. (author)
  • Morrison, Karen E. (author)
  • Opala, Grzegorz (author)
  • Pramstaller, Peter P (author)
  • Pichler, Irene (author)
  • Park, Sung-Sup (author)
  • Quattrone, Aldo (author)
  • Rogaeva, Ekaterina (author)
  • Ross, Owen A. (author)
  • Stefanis, Leonidas (author)
  • Stockton, Joanne D (author)
  • Satake, Wataru (author)
  • Silburn, Peter A. (author)
  • Theuns, Jessie (author)
  • Tan, Eng-King (author)
  • Toda, Tatsushi (author)
  • Tomiyama, Hiroyuki (author)
  • Uitti, Ryan J. (author)
  • Wirdefeldt, KarinKarolinska Institutet (author)
  • Wszolek, Zbigniew K (author)
  • Xiromerisiou, Georgia (author)
  • Puschmann, AndreasLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-aps (author)
  • Yueh, KC (author)
  • Zhao, Y (author)
  • Maraganore, D (author)
  • Kruger, R (author)
  • University of TübingenGerman Center for Neurodegenerative Diseases (DZNE), Bonn (creator_code:org_t)
  • GEO-PD Consortium

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  • In:Neurology79:7, s. 67-6591526-632X

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