SNP-SNP Interactions Discovered by Logic Regression Explain Crohns Disease Genetics 英文参考文献.docVIP

SNP-SNPInteractionsDiscoveredbyLogicRegression ExplainCrohn’sDiseaseGenetics IrinaDinu1.,SurakamethMahasirimongkol2.,QiLiu1,HidekiYanai2,3,NohaSharafEldin1,ErinKreiter1, XuanWu1,ShahabJabbari1,KatsushiTokunaga2,YutakaYasui1* 1School of Public Health, University of Alberta, Edmonton, Alberta, Canada, 2Department of Human Genetics, School of International Health, Graduate School of Medicine,UniversityofTokyo,Tokyo,Japan,3FukujujiHospital,JapanAnti-TuberculosisAssociation,Kiyose,Japan Abstract In genome-wide association studies (GWAS), the association between each single nucleotide polymorphism (SNP) and a phenotypeisassessedstatistically.TofurtherexploregeneticassociationsinGWAS,weconsideredtwospecificformsof biologicallyplausibleSNP-SNPinteractions,‘SNPintersection’and‘SNPunion,’andanalyzedtheCrohn’sDisease(CD)GWAS data of the Wellcome Trust Case Control Consortium for these interactions using a limited form of logic regression. We found strong evidence of CD-association for 195 genes, identifying novel susceptibility genes (e.g., ISX, SLCO6A1, TMEM183A) as well as confirming many previously identified susceptibility genes in CD GWAS (e.g., IL23R, NOD2, CYLD, NKX2-3,IL12RB2,ATG16L1).Notably,37ofthe59chromosomallocationsindicatedforCD-associationbyameta-analysisof CD GWAS, involving over 22,000 cases and 29,000 controls, were represented in the 195 genes, as well as some chromosomallocationspreviouslyindicatedonlyinlinkagestudies,butnotinGWAS.Werepeatedtheanalysiswithtwo smallerGWASsfromtheDatabaseofGenotypeandPhenotype(dbGaP):inspiteofdifferencesofpopulationsandstudy power across the three datasets, we observed some consistencies across the three datasets. Notable examples included TMEM183A and SLCO6A1 which exhibited strong evidence consistently in our WTCCC and both of the dbGaP SNP-SNP interactionanalyses.ExaminingthesespecificformsofSNPinteractionscouldidentifyadditionalgeneticassociationsfrom GWAS. Rcodes, dataexamples, andaReadMefileareavailablefordownload