Nature genetics · 2014

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

СтатьяМетаанализПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод пока не подготовлен

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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, 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), Ashkenazi Jewish Dataset Investigator, Cohorts for Health and 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, 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

Аннотация

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.

Предметные рубрики MeSH

Case-Control Studies Genetic Loci Genetic Predisposition to Disease Genome-Wide Association Study Genotype Humans Parkinson Disease Polymorphism, Single Nucleotide Risk Factors

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

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Аннотация

Предметные рубрики MeSH