Abundant Quantitative Trait Loci Exist for DNA Methylation and Gene Expression in Human Brain 英文参考文献.docVIP

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Abundant Quantitative Trait Loci Exist for DNA Methylation and Gene Expression in Human Brain 英文参考文献.doc

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Abundant Quantitative Trait Loci Exist for DNA Methylation and Gene Expression in Human Brain 英文参考文献

AbundantQuantitativeTraitLociExistforDNA MethylationandGeneExpressioninHumanBrain J.RaphaelGibbs1,2.,MarcelP.vanderBrug1,3.,DenaG.Hernandez1,2.,BryanJ.Traynor1,MichaelA. Nalls1,Shiao-LinLai1,2,SampathArepalli1,AllissaDillman1,IanP.Rafferty1,JuanTroncoso4 ,Robert Johnson5,H.RonaldZielke5,LuigiFerrucci6,DanL.Longo7,MarkR.Cookson1*,AndrewB.Singleton1* 1Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America, 2Department of Molecular NeuroscienceandRetaLilaWestonLaboratories,InstituteofNeurology,UniversityCollegeLondon,London,UnitedKingdom,3DepartmentofMolecularandIntegrative Neurosciences,TheScrippsResearchInstitute,Jupiter,Florida,UnitedStatesofAmerica, 4DivisionofNeuropathology,Department ofPathology,SchoolofMedicine, Johns Hopkins University, Baltimore, Maryland, United States of America, 5National Institute of Child Heath and Human Development Brain and Tissue Bank for DevelopmentalDisorders,UniversityofMarylandMedicalSchool,Baltimore,Maryland,UnitedStatesofAmerica,6ClinicalResearchBranch,NationalInstituteonAging, Baltimore, Maryland, United States of America, 7LymphocyteCell Biology Unit, Laboratory of Immunology, National Institute on Aging, National Institutesof Health, Baltimore,Maryland,UnitedStatesofAmerica Abstract Afundamental challenge in thepost-genome erais tounderstand and annotatetheconsequences ofgenetic variation, particularlywithinthecontextofhumantissues.Wepresentasetofintegratedexperimentsthatinvestigatetheeffectsof common genetic variability on DNA methylation and mRNA expression in four human brain regions each from 150 individuals(600samplestotal).WefindanabundanceofgeneticcisregulationofmRNAexpressionandshowforthefirst time abundant quantitative trait loci for DNA CpG methylation across the genome. We show peak enrichment for cis expression QTLs to be approximately 68,000bp away from individual transcription start sites; however, the peak enrichmentforcisC