Sequential Use of Transcriptional Profiling, Expression Quantitative Trait Mapping, and Gene Association Implicates MMP20 in Human Kidney Aging 英文参考文献.docVIP

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Sequential Use of Transcriptional Profiling, Expression Quantitative Trait Mapping, and Gene Association Implicates MMP20 in Human Kidney Aging 英文参考文献.doc

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Sequential Use of Transcriptional Profiling, Expression Quantitative Trait Mapping, and Gene Association Implicates MMP20 in Human Kidney Aging 英文参考文献

SequentialUseofTranscriptionalProfiling,Expression QuantitativeTraitMapping,andGeneAssociation ImplicatesMMP20inHumanKidneyAging HeatherE.Wheeler1,E.JeffreyMetter2,3,ToshikoTanaka2,3,DevinAbsher4,JohnHiggins5,JacobM. Zahn6,JulieWilhelmy6,RonaldW.Davis6,AndrewSingleton7,RichardM.Myers4,LuigiFerrucci2,3, StuartK.Kim1,8 * 1Department ofGenetics,StanfordUniversity Medical Center, Stanford, California, United States of America, 2Longitudinal Studies Section, Clinical ResearchBranch, NationalInstituteonAging,Baltimore,Maryland,UnitedStatesofAmerica,3MedstarResearchInstitute,Baltimore,Maryland,UnitedStatesofAmerica,4HudsonAlpha InstituteforBiotechnology,Huntsville,Alabama,UnitedStatesofAmerica,5DepartmentofPathology,StanfordUniversityMedicalCenter,Stanford,California,United States of America, 6StanfordGenome Technology Center, PaloAlto,California, United States ofAmerica, 7Laboratory ofNeurogenetics, National Institute onAging, Bethesda,Maryland,UnitedStatesofAmerica,8DepartmentofDevelopmentalBiology,StanfordUniversityMedicalCenter,Stanford,California,UnitedStatesofAmerica Abstract Kidneysageatdifferentrates,suchthatsomepeopleshowlittleornoeffectsofagingwhereasothersshowrapidfunctional decline.Wesequentiallyusedtranscriptionalprofilingandexpressionquantitativetraitloci(eQTL)mappingtonarrowdown whichgenestotestforassociationwithkidneyaging.Wefirstperformedwhole-genometranscriptionalprofilingtofind 630genesthatchangeexpressionwithageinthekidney.UsingtwomethodstodetecteQTLs,wefound101oftheseage- regulatedgenescontainexpression-associatedSNPs.WetestedtheeQTLsforassociationwithkidneyaging,measuredby glomerular filtration rate (GFR) using combined data from the Baltimore Longitudinal Study of Aging (BLSA) and the InCHIANTIstudy.WefoundaSNPassociation(rs1711437inMMP20)withkidneyaging(uncorrectedp=3.661025 ,empirical p=0.01)thatexplains1%–2%ofthevarianceinGFRamongindividuals.Theresultsofthissequentialanalysismayprovide thefirstevidenceforageneassociationwithkidneyaginginhumans. C