2022
Investigating DNA methylation as a mediator of genetic risk in childhood acute lymphoblastic leukemia
Xu K, Li S, Pandey P, Kang AY, Morimoto LM, Mancuso N, Ma X, Metayer C, Wiemels JL, de Smith AJ. Investigating DNA methylation as a mediator of genetic risk in childhood acute lymphoblastic leukemia. Human Molecular Genetics 2022, 31: 3741-3756. PMID: 35717575, PMCID: PMC9616572, DOI: 10.1093/hmg/ddac137.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesSingle nucleotide polymorphismsGenetic risk lociDNA methylationRisk single nucleotide polymorphismsRisk lociAssociation studiesHeritable genetic variationGenome-wide association studiesMost single nucleotide polymorphismsDNA methylation differencesNon-European populationsEpigenetic mechanismsGenetic variationMethylation differencesSignificant DMPsPromoter regionFunctional pathwaysCpG positionsAssociation analysisFunctional roleMethylationNucleotide polymorphismsLociBlood DNA
2021
Epigenome-Wide Association Study of Acute Lymphoblastic Leukemia in Children with Down Syndrome
Li S, Sok P, Xu K, Muskens I, Elliott N, Myint S, Pandey P, Hansen H, Morimoto L, Kang A, Metayer C, Ma X, Mueller B, Roy A, Roberts I, Rabin K, Brown A, Lupo P, Wiemels J, de Smith A. Epigenome-Wide Association Study of Acute Lymphoblastic Leukemia in Children with Down Syndrome. Blood 2021, 138: 214. DOI: 10.1182/blood-2021-151454.Peer-Reviewed Original ResearchEpigenome-wide association studiesB cell proportionsAcute lymphoblastic leukemiaNon-DS populationCell type proportionsDNA methylation dataSingle nucleotide polymorphismsDS-ALLCell proportionAssociation studiesDS controlBlood cell proportionsLymphoblastic leukemiaMethylation dataGenome-wide DNA methylation arraysGenome-wide SNP array dataB-cell acute lymphoblastic leukemiaGenome-wide association studiesLeukemic stem cell functionsDiscovery studiesStem cell functionRecent genome-wide association studiesDNA methylation arraysEpigenome-wide significanceNatural killer cellsThe genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis
Muskens IS, Li S, Jackson T, Elliot N, Hansen HM, Myint SS, Pandey P, Schraw JM, Roy R, Anguiano J, Goudevenou K, Siegmund KD, Lupo PJ, de Bruijn MFTR, Walsh KM, Vyas P, Ma X, Roy A, Roberts I, Wiemels JL, de Smith AJ. The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis. Nature Communications 2021, 12: 821. PMID: 33547282, PMCID: PMC7865055, DOI: 10.1038/s41467-021-21064-z.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesCore Binding Factor Alpha 2 SubunitCpG IslandsDNA MethylationDown SyndromeEpigenesis, GeneticFemaleFetusGATA1 Transcription FactorGenome, HumanGenome-Wide Association StudyHematopoiesisHematopoietic Stem CellsHumansInfant, NewbornLiverMalePromoter Regions, GeneticProto-Oncogene Protein c-fli-1ConceptsDNA methylationGenome-wide impactGenome-wide effectsGenome-wide perturbationsPromoter/enhancer regionEpigenome-wide association studiesAssociation study resultsGene expression changesHematopoietic stem/progenitor cellsCell-type heterogeneityStem/progenitor cellsEpigenome-wide significant CpGsHematopoietic developmentDifferential methylationEpigenetic changesGene expressionPromoter regionEnhancer regionExpression changesAssociation studiesSignificant CpGsImportant regulatorSignificant hypermethylationHematopoietic cellsMethylation
2019
The Genome-Wide Impact of Trisomy 21 on DNA Methylation and Its Implications for Hematologic Malignancies
Wiemels J, Muskens I, Li S, Pandey P, Roy R, Hansen H, Siegmund K, Mueller B, Ma X, Metayer C, de Smith A. The Genome-Wide Impact of Trisomy 21 on DNA Methylation and Its Implications for Hematologic Malignancies. Blood 2019, 134: 2510. DOI: 10.1182/blood-2019-131455.Peer-Reviewed Original ResearchTransient abnormal myelopoiesisNon-DS subjectsDS neonatesDown syndromeTrisomy 21Hematopoietic stem cellsBlood cell proportionsT cellsHigher CD8 T cellsCell proportionEpigenome-wide association studiesMean beta valueNon-DS controlsCD8 T cellsCD4 T cellsLow B cellsAcute lymphoblastic leukemiaAcute megakaryoblastic leukemiaMulti-Ethnic StudyNeonatal DNA methylationEthnicity-stratified analysisSignificant DMRsIllumina Infinium MethylationEPIC arrayChromosome 21Non-Latino whites