Genetic Markers of Adult Obesity Risk Are Associated with Greater Early Infancy Weight Gain and Growth 英文参考文献.docVIP

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Genetic Markers of Adult Obesity Risk Are Associated with Greater Early Infancy Weight Gain and Growth 英文参考文献.doc

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Genetic Markers of Adult Obesity Risk Are Associated with Greater Early Infancy Weight Gain and Growth 英文参考文献

GeneticMarkersofAdultObesityRiskAreAssociated withGreaterEarlyInfancyWeightGainandGrowth CathyE.Elks1,2,RuthJ.F.Loos1,2,StephenJ.Sharp1,2,ClaudiaLangenberg1,2,SusanM.Ring3,NicholasJ. Timpson4,AndrewR.Ness5,GeorgeDaveySmith4,DavidB.Dunger6,NicholasJ.Wareham1,2,KenK. Ong1,2,6 * 1MRCEpidemiologyUnit,Addenbrooke’sHospital,Cambridge,UnitedKingdom,2InstituteofMetabolicScience,Addenbrooke’sHospital,Cambridge,UnitedKingdom, 3DepartmentofSocialMedicine,UniversityofBristol,Bristol,UnitedKingdom,4MRCCentreforCausalAnalysesinTranslationalEpidemiology,DepartmentofSocial Medicine, University of Bristol, Bristol, United Kingdom, 5Department of Oral and Dental Science, University of Bristol, Bristol, United Kingdom, 6Department of Paediatrics,UniversityofCambridge,Cambridge,UnitedKingdom Abstract Background:Genome-widestudieshaveidentifiedseveralcommongeneticvariantsthatarerobustlyassociatedwithadult obesityrisk.Explorationofthesegenotypeassociationsinchildrenmayprovideinsightsintothetimingofweightchanges leadingtoadultobesity. Methods andFindings: ChildrenfromtheAvonLongitudinalStudyofParentsandChildren(ALSPAC) birth cohortwere genotypedfortengeneticvariantspreviouslyassociatedwithadultBMI.Eightvariantsthatshowedindividualassociations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an ‘‘obesity-risk-allele score’’ comprising the total number of risk alleles (range: 2–15 alleles) in each child with complete genotypedata(n=7,146).Repeatedmeasurementsofweight,length/height,andbodymassindexfrombirthtoage11 yearswereexpressedasstandarddeviationscores(SDS).Earlyinfancywasdefinedasbirthtoage6weeks,andearlyinfancy failuretothrivewasdefinedasweightgainbetweenbelowthe5thcentile,adjustedforbirthweight.Theobesity-risk-allele scoreshowedlittleassociationwithbirthweight(regressioncoefficient:0.01SDSperallele;95%CI0.00–0.02),buthadan apparentlymuchlargerpositiveeffectonearlyinfancyweightgain(0.119SDS/allele/year;0.023–0.216)thanon