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Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.

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Authors
Nalls, Mike A
Pankratz, Nathan
Lill, Christina M
Do, Chuong B
Hernandez, Dena G
Saad, Mohamad
DeStefano, Anita L
Kara, Eleanna
Bras, Jose
Sharma, Manu
Schulte, Claudia
Keller, Margaux F
Arepalli, Sampath
Letson, Christopher
Edsall, Connor
Stefansson, Hreinn
Liu, Xinmin
Pliner, Hannah
Lee, Joseph H
Cheng, Rong
Ikram, M Arfan
Ioannidis, John P A
Hadjigeorgiou, Georgios M
Bis, Joshua C
Martinez, Maria
Perlmutter, Joel S
Goate, Alison
Marder, Karen
Fiske, Brian
Sutherland, Margaret
Xiromerisiou, Georgia
Myers, Richard H
Clark, Lorraine N
Stefansson, Kari
Hardy, John A
Heutink, Peter
Chen, Honglei
Wood, Nicholas W
Houlden, Henry
Payami, Haydeh
Brice, Alexis
Scott, William K
Gasser, Thomas
Bertram, Lars
Eriksson, Nicholas
Foroud, Tatiana
Singleton, Andrew B
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Issue Date
2014-09

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Citation
Nat. Genet. 2014, 46 (9):989-93
Abstract
We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation.
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To access publisher's full text version of this article click on the hyperlink at the bottom of the page
Additional Links
http://dx.doi.org/ 10.1038/ng.3043
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146673/
http://www.nature.com/ng/journal/v46/n9/pdf/ng.3043.pdf
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Archived with thanks to Nature genetics
ae974a485f413a2113503eed53cd6c53
10.1038/ng.3043
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English Journal Articles (Peer Reviewed)

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