Gene-Gene Interactions Lead to Higher Risk for Development of Type 2 Diabetes in an Ashkenazi Jewish Population 英文参考文献.docVIP

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Gene-Gene Interactions Lead to Higher Risk for Development of Type 2 Diabetes in an Ashkenazi Jewish Population 英文参考文献.doc

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Gene-Gene Interactions Lead to Higher Risk for Development of Type 2 Diabetes in an Ashkenazi Jewish Population 英文参考文献

Gene-GeneInteractionsLeadtoHigherRiskfor DevelopmentofType2DiabetesinanAshkenaziJewish Population RosalindJ.Neuman1,2*,JonWasson3,GilAtzmon4,JulioWainstein6,YairYerushalmi7,JosephCohen8, NirBarzilai4,IlanaBlech5,BenjaminGlaser5,M.AlanPermutt3 1DepartmentofPsychiatry,WashingtonUniversitySchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica,2DepartmentofGenetics,WashingtonUniversity SchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica,3DepartmentofInternalMedicine,WashingtonUniversitySchoolofMedicine,St.Louis,Missouri,United States of America, 4Institute of Aging, Department of Medicine and Genetics, Albert Einstein College of Medicine, New York, New York, United States of America, 5EndocrinologyandMetabolismService,Hadassah-HebrewUniversityMedicalCenter,Jerusalem,Israel, 6DiabetesUnit,TheE.WolfsonMedicalCenter,Holon,Israel, 7EndocrinologyUnit,ClalitHealthOrganization,Tel-Aviv,Israel,8DiabetesClinic,MacabbiHealthService,TelAviv,Israel Abstract Background: Evidence has accumulated that multiple genetic and environmental factors play important roles in determiningsusceptibilitytotype2diabetes(T2D).Althoughvariantsfromcandidategeneshavebecomeprimetargetsfor genetic analysis, few studies have considered their interplay. Our goal was to evaluate interactions among SNPs within genesfrequentlyidentifiedasassociatedwithT2D. Methods/Principal Findings: Logistic regression was used to study interactions among 4 SNPs, one each from HNF4A[rs1884613],TCF7L2[r,WFS1[r,andKCNJ11[rs5219]inacase-controlAshkenazisampleof974 diabetic subjects and 896 controls. Nonparametric multifactor dimensionality reduction (MDR) and generalized MDR (GMDR)wereusedtoconfirmfindingsfromthelogisticregressionanalysis.HNF4AandWFS1SNPswereassociatedwith T2D in logistic regression analyses [P,0.0001, P,0.0002, respectively]. Interaction between these SNPs werealso strong using parametric or nonparametric methods: the unadjusted odds of being affected with T2D was 3 times gr