Gene-Gene and Gene-Environmental Interactions of Childhood Asthma A Multifactor Dimension Reduction Approach 英文参考文献.docVIP

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Gene-Gene and Gene-Environmental Interactions of Childhood Asthma A Multifactor Dimension Reduction Approach 英文参考文献.doc

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Gene-Gene and Gene-Environmental Interactions of Childhood Asthma A Multifactor Dimension Reduction Approach 英文参考文献

Gene-GeneandGene-EnvironmentalInteractionsof ChildhoodAsthma:AMultifactorDimensionReduction Approach Ming-WeiSu1,Kuan-YenTung1,2,Pi-HuiLiang3,Ching-HuiTsai1,Nai-WeiKuo1,YunglingLeoLee1,2* 1InstituteofEpidemiologyandPreventiveMedicine,CollegeofPublicHealth,NationalTaiwanUniversity,Taipei,Taiwan,2ResearchCenterforGenes,Environmentand HumanHealth,CollegeofPublicHealth,NationalTaiwanUniversity,Taipei,Taiwan,3SchoolofPharmacy,CollegeofMedicine,NationalTaiwanUniversity,Taipei,Taiwan Abstract Background:Theimportanceofgene-geneandgene-environmentinteractionsonasthmaiswelldocumentedinliterature, butasystematicanalysisontheinteractionbetweenvariousgeneticandenvironmentalfactorsisstilllacking. Methodology/Principal Findings: We conducted a population-based, case-control study comprised of seventh-grade childrenfrom14Taiwanesecommunities.Atotalof235asthmaticcasesand1,310non-asthmaticcontrolswereselectedfor DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 single- nucleotidepolymorphismsinantioxidative,inflammatoryandobesity-relatedgenes,andchildhoodasthma.Environmental exposuresanddiseasestatuswereobtainedfromparentalquestionnaires.Themodel-freeandnon-parametricalmultifactor dimensionality reduction (MDR) method was used for the analysis. A three-way gene-gene interaction was elucidated betweenthegenecodingglutathioneS-transferaseP(GSTP1),thegenecodinginterleukin-4receptoralphachain(IL4Ra) and the gene coding insulin induced gene 2 (INSIG2) on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83% with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, includingIL13,beta-2adrenergicreceptor(ADRB2),signaltransducerandactivatoroftranscription6(STAT6).Wealsoused likelihoodratiotestsforinteractionandchi-squareteststovalidateourresultsandalltestsshowedst