资源描述：
《Bringing genome-wide association findings into clinical use.pdf》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
1、REVIEWSTRANSLATIONALGENETICSBringinggenome-wideassociationfindingsintoclinicaluseTeriA. ManolioAbstract
2、Genome-wideassociationstudies(GWASs)havebeenheraldedasamajoradvanceinbiomedicaldiscovery,havingidentified~2,000robustassociationswithcomplexdiseasessince2005.Despitethissu
3、ccess,theyhavemetconsiderablescepticismregardingtheirclinicalapplicability;thisscepticismarisesfromsuchaspectsasthemodesteffectsizesofassociatedvariantsandtheirunclearfunctionalconsequences.Thereare,however,promisingexamplesofGWASfindingsthatwillorthatmaysoonbetranslatedinto
4、clinicalcare.TheseexamplesincludevariantsidentifiedthroughGWASsthatprovidestronglypredictiveorprognosticinformationorthathaveimportantpharmacologicalimplications;theseexamplesmayillustratepromisingapproachestowiderclinicalapplication.Genome-wideassociationstudies(GWASs)haver
5、evo-suggestonlythatadisease-causingvariantresidessome-HeritabilityTheproportionofthetotallutionizedtheidentificationofgenomicregionsassoci-whereinaspecificgenomicregionthatmayincludedoz-phenotypicvariationinatraitatedwithcomplexdiseases.Inthepast7 years,moreensofnearbygenesa
6、ndvariants.Andalthoughsomethatcanbeattributedtothan1,600publicationshaveidentified~2,000robustGWASfindingshaveidentifiedpreviouslyunknowngeneticeffects.associationswithmorethan300complexdiseasesandpathogenicpathways,suchascomplement-mediatedtraits.Thesenumbersareordersofmagn
7、itudegreaterinflammationinmaculardegeneration14andautophagyOddsratiosthanthoseofreplicablelinkageandcandidategeneinCrohn’sdisease15,16,thesehaveyettofindmajorAmeasureofeffectsize.Definedastheratiooftheassociationfindingstodateforcomplexdiseases.Initialclinicalapplications.od
8、ds(thatis,theprobabilityofeuphoriaatthisveritablehoardofreliableassocia-Despitetheadventofnewertechnologies,particu-diseasedividedby1minusthetions,totallingnearly100ormoreforsometraits1,2,haslarlysequencing-basedmethodsforidentifyingdisease-probability)ofadiseasebeingobserve
9、dinonegroupofdimmedsomewhatwiththerecognitionthatGWAS-associatedvariants,as
