线上尿液代谢产物的遗传研讨揭示人类排毒和吸

浏览量: 86   / 时间:2020-01-27   /作者:线上体育平台
常州杰森家具有限公司

Author:PascalSchlosser,YongLi,PeggySekula,JohannesRaffler,FranziskaGrundner-Culemann,MaikPietzner,YurongCheng,MatthiasWuttke,IngaSteinbrenner,UllaT.Schultheiss,FruzsinaKotsis,TimKacprowski,LukasForer,BirgitHausknecht,ArifB.Ekici,MatthiasNauck,UweVlker,GerdWalz,PeterJ.Oefner,FlorianKronenberg,RobertP.Mohney,MichaelKttgen,KarstenSuhre,Kai-UweEckardt,GabiKastenmller,AnnaKttgen

Abstract:Thekidneysintegrateinformationfromcontinuoussystemicprocessesrelatedtotheabsorption,distribution,metabolismandexcretion(ADME)ofmetabolites.Toidentifyunderlyingmolecularmechanisms,weperformedgenome-wideassociationstudiesoftheurinaryconcentrationsof1,172metabolitesamong1,627patientswithreducedkidneyfunction.The240uniquemetabolite–locusassociations(metabolitequantitativetraitloci,mQTLs)thatwereidentifiedandreplicatedhighlightnovelcandidatesubstratesfortransportproteins.TheidentifiedgenesareenrichedinADME-relevanttissuesandcelltypes,andtheyrevealnovelcandidatesforbiotransformationanddetoxificationreactions.FinemappingofmQTLsandintegrationwithsingle-cellgeneexpressionpermittedtheprioritizationofcausalgenes,functionalvariantsandtargetcelltypes.ThecombinationofmQTLswithgeneticandhealthinformationfrom450,000UKBiobankparticipantsilluminatedmetabolicmediators,andhence,novelurinarybiomarkersofdiseaserisk.ThiscomprehensiveresourceofgenetictargetsandtheirsubstratesisinformativeforADMEprocessesinhumansandisrelevanttobasicscience,clinicalmedicineandpharmaceuticalresearch.