04090nas a2200949 4500008004100000022001400041245011600055210006900171260001300240300001100253490000700264520106600271653002501337653001701362653003801379653003401417653001301451653001101464653002201475653003601497653001701533100001901550700002101569700002301590700001801613700002301631700001801654700002401672700001801696700001501714700001701729700002101746700002301767700002201790700002401812700001901836700002301855700001601878700001901894700001901913700001601932700002001948700002501968700003101993700001902024700002002043700002402063700001802087700001802105700001702123700002502140700002602165700002202191700002302213700002102236700001902257700001902276700001802295700002202313700001902335700001902354700001802373700002202391700001902413700001802432700002302450700002002473700002502493710006602518710010002584710001202684710001102696710004502707710004702752710004202799710007502841710005502916710005502971710004103026710003703067856003603104 2014 eng d a1546-171800aLarge-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.0 aLargescale metaanalysis of genomewide association data identifie c2014 Sep a989-930 v463 a
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.
10aCase-Control Studies10aGenetic Loci10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aGenotype10aHumans10aParkinson Disease10aPolymorphism, Single Nucleotide10aRisk Factors1 aNalls, Mike, A1 aPankratz, Nathan1 aLill, Christina, M1 aDo, Chuong, B1 aHernandez, Dena, G1 aSaad, Mohamad1 aDeStefano, Anita, L1 aKara, Eleanna1 aBras, Jose1 aSharma, Manu1 aSchulte, Claudia1 aKeller, Margaux, F1 aArepalli, Sampath1 aLetson, Christopher1 aEdsall, Connor1 aStefansson, Hreinn1 aLiu, Xinmin1 aPliner, Hannah1 aLee, Joseph, H1 aCheng, Rong1 aIkram, Arfan, M1 aIoannidis, John, P A1 aHadjigeorgiou, Georgios, M1 aBis, Joshua, C1 aMartinez, Maria1 aPerlmutter, Joel, S1 aGoate, Alison1 aMarder, Karen1 aFiske, Brian1 aSutherland, Margaret1 aXiromerisiou, Georgia1 aMyers, Richard, H1 aClark, Lorraine, N1 aStefansson, Kari1 aHardy, John, A1 aHeutink, Peter1 aChen, Honglei1 aWood, Nicholas, W1 aHoulden, Henry1 aPayami, Haydeh1 aBrice, Alexis1 aScott, William, K1 aGasser, Thomas1 aBertram, Lars1 aEriksson, Nicholas1 aForoud, Tatiana1 aSingleton, Andrew, B1 aInternational Parkinson's Disease Genomics Consortium (IPDGC)1 aParkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI)1 a23andMe1 aGenePD1 aNeuroGenetics Research Consortium (NGRC)1 aHussman Institute of Human Genomics (HIHG)1 aAshkenazi Jewish Dataset Investigator1 aCohorts for Health and Aging Research in Genetic Epidemiology (CHARGE)1 aNorth American Brain Expression Consortium (NABEC)1 aUnited Kingdom Brain Expression Consortium (UKBEC)1 aGreek Parkinson's Disease Consortium1 aAlzheimer Genetic Analysis Group uhttps://chs-nhlbi.org/node/6789