Evidence for Significant Overlap between Common Risk Variants for Crohns Disease and Ankylosing Spondylitis 英文参考文献.docVIP

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Evidence for Significant Overlap between Common Risk Variants for Crohns Disease and Ankylosing Spondylitis 英文参考文献.doc

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Evidence for Significant Overlap between Common Risk Variants for Crohns Disease and Ankylosing Spondylitis 英文参考文献

EvidenceforSignificantOverlapbetweenCommonRisk VariantsforCrohn’sDiseaseandAnkylosingSpondylitis DebbyLaukens1,MichelGeorges2,Ce′cileLibioulle2,CynthiaSandor2,MyriamMni2,BertVander Cruyssen3,HaraldPeeters1,DirkElewaut3.,MartineDeVos1*. 1DepartmentofGastroenterology,GhentUniversity,Ghent,Belgium,2UnitofAnimalGenomics,GIGA-RandFacultyofVeterinaryMedicine,UniversityofLie`ge, Lie`ge, Belgium,3DepartmentofRheumatology,GhentUniversity,Ghent,Belgium Abstract Background: A multicenter genome-wide association scan for Crohn’s Disease (CD) has recently reported 40 CD susceptibilityloci,including29novelones(19significantand10putative).Togaininsightintothegeneticoverlapbetween CDandankylosingspondylitis(AS),thesemarkersweretestedforassociationinASpatients. Principal Findings: Two previously established associations, namely with the MHC and IL23R loci, were confirmed. In addition,rs2872507,whichmapstoalocusassociatedwithasthmaandinfluencestheexpressionoftheORMDL3genein lymphoblastoidcells,showedasignificantassociationwithAS(p=0.03).IngutbiopsiesofASandCDpatients,ORMDL3 expression was not significantly different from controls and no correlation was found with the rs2872507 genotype (Spearman’srho:20.067).Thedistributionofp-valuesfortheremaining36SNPswassignificantlyskewedtowardslowp- valuesunlessthetop5rankedSNPs(ORMDL3,NKX2–3,PTPN2,ICOSLGandMST1)wereexcludedfromtheanalysis. Conclusions:AssociationanalysisusingriskvariantsforCDledtotheidentificationofanewriskvariantassociatedwithAS (ORMDL3),underscoringaroleforERstressinAS.Inaddition,twoknownandfivepotentiallyrelevantassociationswere detected,contributingtocommonsusceptibilityofCDandAS. Citation:LaukensD,GeorgesM,LibioulleC,SandorC,MniM,etal.(2010)EvidenceforSignificantOverlapbetweenCommonRiskVariantsforCrohn’sDisease andAnkylosingSpondylitis.PLoSONE5(11):e13795.doi:10.1371/journal.pone.0013795 Editor:AntjeTimmer,HelmholtzZentrumMu¨nchen,Germany ReceivedJuly8,2009;AcceptedSeptember27,2010;PublishedNovember2,2010 Copyr