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Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.
Tuesday,2015-08-18 11:34 America/Los_Angeles — zdrager
| Title | Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Nalls, MA, Pankratz, N, Lill, CM, Do, CB, Hernandez, DG, Saad, M, DeStefano, AL, Kara, E, Bras, J, Sharma, M, Schulte, C, Keller, MF, Arepalli, S, Letson, C, Edsall, C, Stefansson, H, Liu, X, Pliner, H, Lee, JH, Cheng, R, Ikram, AM, Ioannidis, JPA, Hadjigeorgiou, GM, Bis, JC, Martinez, M, Perlmutter, JS, Goate, A, Marder, K, Fiske, B, Sutherland, M, Xiromerisiou, G, Myers, RH, Clark, LN, Stefansson, K, Hardy, JA, Heutink, P, Chen, H, Wood, NW, Houlden, H, Payami, H, Brice, A, Scott, WK, Gasser, T, Bertram, L, Eriksson, N, Foroud, T, Singleton, AB |
| Corporate/Institutional Authors | 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 |
| Journal | Nat Genet |
| Volume | 46 |
| Issue | 9 |
| Pagination | 989-93 |
| Date Published | 2014 Sep |
| ISSN | 1546-1718 |
| Keywords | Case-Control Studies, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Parkinson Disease, Polymorphism, Single Nucleotide, Risk Factors |
| Abstract | <p>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.</p> |
| DOI | 10.1038/ng.3043 |
| Alternate Journal | Nat. Genet. |
| PubMed ID | 25064009 |
| PubMed Central ID | PMC4146673 |
| Grant List | 076113 / / Wellcome Trust / United Kingdom 083948/Z/07/Z / / Wellcome Trust / United Kingdom 085475 / / Wellcome Trust / United Kingdom 089698 / / Wellcome Trust / United Kingdom 090355 / / Wellcome Trust / United Kingdom 1K23NS070867 / NS / NINDS NIH HHS / United States 1KL2RR024154 / RR / NCRR NIH HHS / United States 2UL1 RR024156 / RR / NCRR NIH HHS / United States AG023629 / AG / NIA NIH HHS / United States AG025259 / AG / NIA NIH HHS / United States AG031287 / AG / NIA NIH HHS / United States AG033193 / AG / NIA NIH HHS / United States AG08122 / AG / NIA NIH HHS / United States AG16495 / AG / NIA NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States G-0907 / / Parkinson's UK / United Kingdom G-0909 / / Parkinson's UK / United Kingdom G0700943 / / Medical Research Council / United Kingdom G0701075 / / Medical Research Council / United Kingdom G0802462 / / Medical Research Council / United Kingdom G0802760 / / Medical Research Council / United Kingdom G0901254 / / Medical Research Council / United Kingdom G1100479 / / Medical Research Council / United Kingdom J-0804 / / Parkinson's UK / United Kingdom K02 NS073836 / NS / NINDS NIH HHS / United States MC_G0901330 / / Medical Research Council / United Kingdom MC_G1000735 / / Medical Research Council / United Kingdom MC_PC_09003 / / Medical Research Council / United Kingdom MR/L016400/1 / / Medical Research Council / United Kingdom MR/L501554/1 / / Medical Research Council / United Kingdom NS036630 / NS / NINDS NIH HHS / United States NS050487 / NS / NINDS NIH HHS / United States NS060113 / NS / NINDS NIH HHS / United States NS17950 / NS / NINDS NIH HHS / United States P30AG013846 / AG / NIA NIH HHS / United States P30AG024826 / AG / NIA NIH HHS / United States P50 NS038377 / NS / NINDS NIH HHS / United States P50 NS071674 / NS / NINDS NIH HHS / United States P50NS071674 / NS / NINDS NIH HHS / United States R01 NS076843 / NS / NINDS NIH HHS / United States R01 NS088538 / NS / NINDS NIH HHS / United States R01-NS-36960 / NS / NINDS NIH HHS / United States R01CA141668 / CA / NCI NIH HHS / United States R01NS037167 / NS / NINDS NIH HHS / United States R44 HG006981 / HG / NHGRI NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States UL1 TR001108 / TR / NCATS NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States WT089698 / / Wellcome Trust / United Kingdom WT089698/Z/09/Z / / Wellcome Trust / United Kingdom Z01 AG000932-01 / / Intramural NIH HHS / United States Z01 AG000949-03 / / Intramural NIH HHS / United States |