Parent-Of-Origin Effects in Autism Identified through Genome-Wide Linkage Analysis of 16,000 SNPs 英文参考文献.docVIP

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Parent-Of-Origin Effects in Autism Identified through Genome-Wide Linkage Analysis of 16,000 SNPs 英文参考文献.doc

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Parent-Of-Origin Effects in Autism Identified through Genome-Wide Linkage Analysis of 16,000 SNPs 英文参考文献

Parent-Of-OriginEffectsinAutismIdentifiedthrough Genome-WideLinkageAnalysisof16,000SNPs DelphineFradin1,2,KeelyCheslack-Postava3,ChristineLadd-Acosta2,CraigNewschaffer4, AravindaChakravarti5,DanE.Arking5,AndrewFeinberg2,M.DanieleFallin1* 1DepartmentofEpidemiology,BloombergSchoolofPublicHealth,JohnsHopkinsUniversity,Baltimore,Maryland,UnitedStatesofAmerica,2DepartmentofMedicine, CenterforEpigenetics,InstituteforBasicBiomedicalSciences,JohnsHopkinsUniversitySchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica,3RobertWood JohnsonFoundationHealthSocietyScholars,ColumbiaUniversity,NewYork,NewYork,UnitedStatesofAmerica,4DepartmentofEpidemiology,DrexelUniversity, Philadelphia,Pennsylvania,UnitedStatesofAmerica,5CenterforComplexDiseaseGenomics,McKusick-NathansInstituteofGeneticMedicine,JohnsHopkinsUniversity, Baltimore,Maryland,UnitedStatesofAmerica Abstract Background: Autism is a common heritable neurodevelopmental disorder with complex etiology. Several genome-wide linkage and association scans have been carried out to identify regions harboring genes related to autism or autism spectrum disorders, with mixed results. Given the overlap in autism features with genetic abnormalities known to be associatedwithimprinting,onepossiblereasonforlackofconsistencywouldbetheinfluenceofparent-of-origineffects thatmaymasktheabilitytodetectlinkageandassociation. Methods and Findings: We have performed a genome-wide linkage scan that accounts for potential parent-of-origin effectsusing16,311SNPsamongfamiliesfromtheAutismGeneticResourceExchange(AGRE)andtheNationalInstituteof MentalHealth(NIMH)autismrepository.Wereportparametric(GH,Genehunter)andallele-sharinglinkage(Aspex)results usingabroadspectrumdisordercasedefinition.Paternal-origingenome-widestatisticallysignificantlinkagewasobserved onchromosomes4(LODGH=3.79,empiricalp,0.005andLODAspex=2.96,p=0.008),15(LODGH=3.09,empiricalp,0.005 andLODAspex=3.62,empiricalp=0.003)and20(LODGH=3.36,empiricalp,0.005andLODAspex=3.38,empiricalp=0.