On the Use of Variance per Genotype as a Tool to Identify Quantitative Trait Interaction Effects A Report from the Womens Genome Health Study 英文参考文献.docVIP

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On the Use of Variance per Genotype as a Tool to Identify Quantitative Trait Interaction Effects A Report from the Womens Genome Health Study 英文参考文献.doc

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On the Use of Variance per Genotype as a Tool to Identify Quantitative Trait Interaction Effects A Report from the Womens Genome Health Study 英文参考文献

OntheUseofVarianceperGenotypeasaToolto IdentifyQuantitativeTraitInteractionEffects:AReport fromtheWomen’sGenomeHealthStudy GuillaumePare′1,2*,NancyR.Cook2,PaulM.Ridker2,DanielI.Chasman2 1Department of Pathology and Molecular Medicine, Population Genomics Program, McMaster University, Hamilton, Canada, 2Department of Preventive Medicine, BrighamandWomen’sHospital,Boston,Massachusetts,UnitedStatesofAmerica Abstract Testingforgeneticeffectsonmeanvaluesofaquantitativetraithasbeenaverysuccessfulstrategy.However,moststudies to date have not explored genetic effects on the variance of quantitative traits as a relevant consequence of genetic variation.Inthisreport,wedemonstratethat,underplausiblescenariosofgeneticinteraction,thevarianceofaquantitative traitisexpectedtodifferamongthethreepossiblegenotypesofabiallelicSNP.LeveragingthisobservationwithLevene’s test of equality of variance, we propose a novel method to prioritize SNPs for subsequent gene–gene and gene– environmenttesting.Thismethodhastheadvantageouscharacteristicthattheinteractingcovariateneednotbeknownor measuredforaSNPtobeprioritized.Usingsimulations,weshowthatthismethodhasincreasedpoweroverexhaustive search under certain conditions. Wefurther investigatethe utilityof variance per genotypeby examiningdata fromthe Women’sGenomeHealthStudy.Usingthisdataset,weidentifynewinteractionsbetweentheLEPRSNPrnd body mass index in the prediction of C-reactive protein levels, between the ICAM1 SNP rs1799969 and smoking in the prediction of soluble ICAM-1 levels, and between the PNPLA3 SNP rs738409 and body mass index in the prediction of soluble ICAM-1 levels. These results demonstrate the utility of our approach and provide novel genetic insight into the relationshipamongobesity,smoking,andinflammation. Citation:Pare′G,CookNR,RidkerPM,ChasmanDI(2010)OntheUseofVarianceperGenotypeasaTooltoIdentifyQuantitativeTraitInteractionEffects:AReport fromtheWomen’sGenomeHealthStudy.PLoSGenet6(6):e1000981.doi:10.1371/journal