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1、ThenewenglandjournalofmedicineoriginalarticleALarge-Scale,Consortium-BasedGenomewideAssociationStudyofAsthmaMiriamF.Moffatt,D.Phil.,IvoG.Gut,Ph.D.,FlorenceDemenais,M.D.,DavidP.Strachan,M.D.,EmmanuelleBouzigon,M.D.,Ph.D.,SimonHeath,Ph.D.,ErikavonMutius,M.D.,MartinFarrall,F.R.C.Path.,M
2、arkLathrop,Ph.D.,andWilliamO.C.M.Cookson,M.D.,D.Phil.,fortheGABRIELConsortium*AbstractBackgroundSusceptibilitytoasthmaisinfluencedbygenesandenvironment;implicatedgenesFromtheNationalHeartandLungInmayindicatepathwaysfortherapeuticintervention.Geneticriskfactorsmaybeuse-stitute,Imperia
3、lCollege(M.F.M.,W.O.C.M.C.),theDivisionofCommunityfulinidentifyingsubtypesofasthmaanddeterminingwhetherintermediatepheno-HealthSciences,St.George’s,Universitytypes,suchaselevationofthetotalserumIgElevel,arecausallylinkedtodisease.ofLondon(D.P.S.),andRoyalBromptonandHarefieldNHSFounda
4、tionTrust(W.O.C.M.C.)—allinLondon;CommisMethodssariatàl’EnergieAtomique,InstitutdeWecarriedoutagenomewideassociationstudybygenotyping10,365personswithGénomique,CentreNationaldeGénophysician-diagnosedasthmaand16,110unaffectedpersons,allofwhomwerematchedtypage,Evry,France(I.G.G.,S.H.,M
5、.L.);INSERM,Unité946,FondationJeanforancestry.Weusedrandom-effectspooledanalysistotestforassociationintheDausset–Centred’EtudeduPolymoroverallstudypopulationandinsubgroupsofsubjectswithchildhood-onsetasthmaphismeHumain(CEPH)(F.D.,E.B.),Fon(definedasasthmadevelopingbefore16yearsofage)
6、,later-onsetasthma,severedationJeanDausset–CEPH(F.D.,E.B.,M.L.),andUniversitéParisDiderotParis7,asthma,andoccupationalasthma.InstitutUniversitaired’Hématologie(F.D.,E.B.)—allinParis;UniversityChildren’sResultsHospital,AsthmaandAllergyDepartment,LudwigMaximiliansUniversity,Weobserveda
7、ssociationsofgenomewidesignificancebetweenasthmaandthefol-Munich,Germany(E.M.);andWellcomelowingsingle-nucleotidepolymorphisms:rs3771166onchromosome2,implicat-TrustCentreforHumanGenetics,UniveringIL1RL1/IL18R1(P=3×10−9);rs9273349onchromosome6,implicatingHLA-DQsityofOxford,Oxford,Unit
8、edKingdom(M.