Method for Evaluating Multiple Mediators Mediating Effects of Smoking and COPD on the Association between the CHRNA5-A3 Variant and Lung Cancer Risk 英文参考文献.docVIP

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Method for Evaluating Multiple Mediators Mediating Effects of Smoking and COPD on the Association between the CHRNA5-A3 Variant and Lung Cancer Risk 英文参考文献.doc

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Method for Evaluating Multiple Mediators Mediating Effects of Smoking and COPD on the Association between the CHRNA5-A3 Variant and Lung Cancer Risk 英文参考文献

MethodforEvaluatingMultipleMediators:Mediating EffectsofSmokingandCOPDontheAssociation betweentheCHRNA5-A3VariantandLungCancerRisk JianWang1,4,MargaretR.Spitz2,ChristopherI.Amos3,XifengWu4,DavidW.Wetter5,PaulM.Cinciripini6, SanjayShete1,4 * 1DepartmentofBiostatistics,TheUniversityofTexasMDAndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica, 2DepartmentofMolecularandCellular Biology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America, 3Department of Genetics, The University of Texas MD AndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica,4DepartmentofEpidemiology,TheUniversityofTexasMDAndersonCancerCenter,Houston,Texas, UnitedStatesofAmerica,5DepartmentofHealthDisparitiesResearch,TheUniversityofTexasMDAndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica, 6DepartmentofBehavioralScience,TheUniversityofTexasMDAndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica Abstract Amediationmodelexploresthedirectandindirecteffectsbetweenanindependentvariableandadependentvariableby includingothervariables(ormediators).Mediationanalysishasrecentlybeenusedtodissectthedirectandindirecteffects of genetic variants on complex diseases using case-control studies. However, bias could arise in the estimations of the geneticvariant-mediatorassociationbecausethepresenceorabsenceofthemediatorinthestudysamplesisnotsampled following the principles of case-control study design. In this case, the mediation analysis using data from case-control studies might lead to biased estimates of coefficients and indirect effects. In this article, we investigated a multiple- mediationmodelinvolvingathree-pathmediatingeffectthroughtwomediatorsusingcase-controlstudydata.Wepropose anapproachtocorrectbiasincoefficientsandprovideaccurateestimatesofthespecificindirecteffects.Ourapproachcan also be used when the original case-control study is frequency matched on one of the mediators. We employed bootstrappingtoassessthesignificanceofindirect