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

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3087558 59 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2014 Nature America, Inc. All rights reserved.
Έτος δημοσίευσης:
2014
Συγγραφείς:
Nalls, M.A.
Pankratz, N.
Lill, C.M.
Do, C.B.
Hernandez, D.G.
Saad, M.
Destefano, A.L.
Kara, E.
Bras, J.
Sharma, M.
Schulte, C.
Keller, M.F.
Arepalli, S.
Letson, C.
Edsall, C.
Stefansson, H.
Liu, X.
Pliner, H.
Lee, J.H.
Cheng, R.
Ikram, M.A.
Ioannidis, J.P.A.
Hadjigeorgiou, G.M.
Bis, J.C.
Martinez, M.
Perlmutter, J.S.
Goate, A.
Marder, K.
Fiske, B.
Sutherland, M.
Xiromerisiou, G.
Myers, R.H.
Clark, L.N.
Stefansson, K.
Hardy, J.A.
Heutink, P.
Chen, H.
Wood, N.W.
Houlden, H.
Payami, H.
Brice, A.
Scott, W.K.
Gasser, T.
Bertram, L.
Eriksson, N.
Foroud, T.
Singleton, A.B.
Plagnol, V.
Sheerin, U.-M.
Simón-Sánchez, J.
Lesage, S.
Sveinbjörnsdóttir, S.
Barker, R.
Ben-Shlomo, Y.
Berendse, H.W.
Berg, D.
Bhatia, K.
de Bie, R.M.A.
Biffi, A.
Bloem, B.
Bochdanovits, Z.
Bonin, M.
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Brockmann, K.
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Clark, L.N.
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Fahn, S.
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Martin, E.R.
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Choi, S.H.
Frank, S.
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Psaty, B.M.
Rice, K.
Longstreth, W.T., Jr.
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van Duijn, C.M.
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Verlinden, V.J.
Koudstaal, P.J.
Singleton, A.
Cookson, M.
Gibbs, J.R.
Hernandez, D.
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Zonderman, A.
Ferrucci, L.
Johnson, R.
Longo, D.
O'brien, R.
Traynor, B.
Troncoso, J.
van der Brug, M.
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Weale, M.
Ramasamy, A.
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Spanaki, C.
Plaitakis, A.
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Stefanis, L.
Vassilatis, D.
Koutsis, G.
Panas, M.
Hadjigeorgiou, G.M.
Lunnon, K.
Lupton, M.
Powell, J.
Parkkinen, L.
Ansorge, O.
International Parkinson's Disease Genomics Consortium (IPDGC)
Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI)
23andMe
GenePD
NeuroGenetics Research Consortium (NGRC)
Hussman Institute of Human Genomics (HIHG)
The Ashkenazi Jewish Dataset Investigator
Cohorts for Health
Aging Research in Genetic Epidemiology (CHARGE)
North American Brain Expression Consortium (NABEC)
United Kingdom Brain Expression Consortium (UKBEC)
Greek Parkinson's Disease Consortium
Alzheimer Genetic Analysis Group
Περιοδικό:
Nature Genetics
Εκδότης:
Lithuanian Nature Research Centre
Τόμος:
46
Αριθμός / τεύχος:
9
Σελίδες:
989-993
Λέξεις-κλειδιά:
Article; DNA methylation; gene expression; gene identification; gene locus; genetic association; genetic risk; genetic variability; human; Parkinson disease; priority journal; risk assessment; single nucleotide polymorphism; case control study; genetic predisposition; genetics; genome-wide association study; genotype; meta analysis; Parkinson disease; procedures; risk factor, Case-Control Studies; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Parkinson Disease; Polymorphism, Single Nucleotide; Risk Factors
Επίσημο URL (Εκδότης):
DOI:
10.1038/ng.3043
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