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

Nalls, M. A., Pankratz, N., Lill, C. M., Do, C. B., Hernandez, D. G., Saad, M., et al. (2014). Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nature Genetics, 46(9), 989-993. doi:10.1038/ng.3043.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0026-AA42-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0026-AA43-6
Genre: Journal Article

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 Creators:
Nalls, Mike A, Author
Pankratz, Nathan, Author
Lill, Christina M.1, Author              
Do, Chuong B, Author
Hernandez, Dena G., Author
Saad, Mohamad, Author
DeStefano, Anita L., Author
Kara, Eleanna, Author
Bras, Jose, Author
Sharma, Manu, Author
Schulte, Claudia, Author
Keller, Margaux F., Author
Arepalli, Sampath, Author
Letson, Christopher, Author
Edsall, Connor, Author
Stefansson, Hreinn, Author
Liu, Xinmin, Author
Pliner, Hannah, Author
Lee, Joseph H., Author
Cheng, Rong, Author
Ikram, M. Arfan, AuthorIoannidis, John P.A., AuthorHadjigeorgiou, Georgios M., AuthorBis, Joshua C., AuthorMartinez, Maria, AuthorPerlmutter, Joel S., AuthorGoate, Alison, AuthorMarder, Karen, AuthorFiske, Brian, AuthorSutherland, Margaret, AuthorXiromerisiou, Georgia, AuthorMyers, Richard H., AuthorClark, Lorraine N, AuthorStefansson, Kari, AuthorHardy, John A., AuthorHeutink, Peter, AuthorChen, Honglei, AuthorWood, Nicholas W., AuthorHoulden, Henry, AuthorPayami, Haydeh, AuthorBrice, Alexis, AuthorScott, William K, AuthorGasser, Thomas, AuthorBertram, Lars1, Author              Eriksson, Nicholas, AuthorForoud, Tatiana, AuthorSingleton, Andrew B., Author more..
Affiliations:
1Neuropsychiatric Genetics (Lars Bertram), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479655              

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 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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Language(s): eng - English
 Dates: 2014-07-272014-09
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: Other: accessionPMC4146673
PMID: 25064009
DOI: 10.1038/ng.3043
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Title: Nature Genetics
  Other : Nature Genet.
Source Genre: Journal
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Publ. Info: New York, NY : Nature America, Inc.
Pages: - Volume / Issue: 46 (9) Sequence Number: - Start / End Page: 989 - 993 Identifier: ISSN: 1061-4036
CoNE: https://pure.mpg.de/cone/journals/resource/954925598609