Prediction of Expected Years of Life Using Whole-Genome Markers 英文参考文献.docVIP

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Prediction of Expected Years of Life Using Whole-Genome Markers 英文参考文献.doc

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Prediction of Expected Years of Life Using Whole-Genome Markers 英文参考文献

PredictionofExpectedYearsofLifeUsingWhole- GenomeMarkers GustavodelosCampos*,YannC.Klimentidis,AnaI.Vazquez,DavidB.Allison SectiononStatisticalGenetics,DepartmentofBiostatistics,UniversityofAlabamaatBirmingham,Birmingham,Alabama,UnitedStatesofAmerica Abstract Genetic factors are believed to account for 25% of the interindividual differences in Years of Life (YL) among humans. However,thegeneticlocithathavethusfarbeenfoundtobeassociatedwithYLexplainaverysmallproportionofthe expected genetic variation in this trait, perhaps reflecting the complexity of the trait and the limitations of traditional association studies when applied to traits affected by a large number of small-effect genes. Using data from the Framingham Heart Study and statistical methods borrowed largely from the field of animal genetics (whole-genome prediction,WGP),wedevelopedaWGPmodelforthestudyofYLandevaluatedtheextenttowhichthousandsofgenetic variantsacrossthegenomeexaminedsimultaneouslycanbeusedtopredictinterindividualdifferencesinYL.Wefindthata sizableproportionofdifferencesinYL—whichwereunexplainedbyageatentry,sex,smokingandBMI—canbeaccounted forandpredictedusingWGPmethods.Thecontributionofgenomicinformationtopredictionaccuracywasevenhigher thanthatofsmokingandbodymassindex(BMI)combined;twopredictorsthatareconsideredamongthemostimportant life-shorteningfactors.Weevaluatedtheimpactsoffamilialrelationshipsandpopulationstructure(asdescribedbythefirst twomarker-derivedprincipalcomponents)andconcludedthatinourdatasetpopulationstructureexplainedpartially,but notfullythegainsinpredictionaccuracyobtainedwithWGP.Furtherinspectionofpredictionaccuraciesbyageatdeath indicatedthatmostofthegainsinpredictiveabilityachievedwithWGPwereduetotheincreasedaccuracyofpredictionof earlymortality,perhapsreflectingtheabilityofWGPtocapturedifferencesingeneticrisktodeadlydiseasessuchascancer, whicharemostoftenresponsibleforearlymortalityinoursample. Citation: delosCampos G,KlimentidisYC, VazquezAI,Allison DB(2012)Pred