Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology 英文参考文献.docVIP

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Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology 英文参考文献.doc

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Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology 英文参考文献

ProteinsEncodedinGenomicRegionsAssociatedwith Immune-MediatedDiseasePhysicallyInteractand SuggestUnderlyingBiology ElizabethJ.Rossin1,2,3,4,5,KasperLage2,3,6,7,SoumyaRaychaudhuri1,2,8,RamnikJ.Xavier1,2,3 DianaTatar6,YairBenita1, InternationalInflammatoryBowelDiseaseGeneticsConstortium, ChrisCotsapas1,2.,MarkJ.Daly1,2,3,4,5. , * 1CenterforHumanGeneticsResearchandCenterforComputationalandIntegrativeBiology,MassachusettsGeneralHospital,Boston,Massachusetts,UnitedStatesof America,2PrograminMedicalandPopulationGenetics,TheBroadInstitute,Cambridge,Massachusetts,UnitedStatesofAmerica,3DepartmentofMedicine,Harvard Medical School, Boston, Massachusetts, United States of America, 4Health Science and Technology MD Program, Harvard University and Massachusetts Institute of Technology,Boston,Massachusetts,UnitedStatesofAmerica,5HarvardBiologicalandBiomedicalSciencesProgram,HarvardUniversity,Boston,Massachusetts,United StatesofAmerica,6PediatricSurgicalResearchLaboratories,MassachusettsGeneralHospital,Boston,Massachusetts,UnitedStatesofAmerica, 7CenterforBiological SequenceAnalysis,DepartmentofSystemsBiology,TechnicalUniversityofDenmark,Lyngby,Denmark,8DivisionofRheumatology,Immunology,andAllergy,Brigham andWomen’sHospital,Boston,Massachusetts,UnitedStatesofAmerica Abstract Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposingtoimmune-mediateddisease.Inferringdiseasebiologyfromtheseobservations,however,hingesonourability todiscoverthemolecularprocessesbeingperturbedbytheseriskvariants.Ithaspreviouslybeenobservedthatdifferent genesharboringcausalmutationsforthesameMendeliandiseaseoftenphysicallyinteract.Wesoughttoevaluatethedegree towhichthisistrueofgeneswithinstronglyassociatedlociincomplexdisease.Usingsetsoflocidefinedinrheumatoid arthritis(RA)andCrohn’sdisease(CD)GWAS,webuildprotein–proteininteraction(PPI)networksforgeneswithinassociated lociandfindabundantphysicalinteractionsbetweenproteinprodu