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 ResearchMeSH KeywordsDNA MethylationGenome-Wide Association StudyHumansPolymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaTranscription FactorsConceptsEpigenome-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
Genome-wide trans-ethnic meta-analysis identifies novel susceptibility loci for childhood acute lymphoblastic leukemia
Jeon S, de Smith AJ, Li S, Chen M, Chan TF, Muskens IS, Morimoto LM, DeWan AT, Mancuso N, Metayer C, Ma X, Wiemels JL, Chiang CWK. Genome-wide trans-ethnic meta-analysis identifies novel susceptibility loci for childhood acute lymphoblastic leukemia. Leukemia 2021, 36: 865-868. PMID: 34750507, PMCID: PMC9075725, DOI: 10.1038/s41375-021-01465-1.Peer-Reviewed Original ResearchMeSH KeywordsChildGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaGenetic determinants of blood-cell traits influence susceptibility to childhood acute lymphoblastic leukemia
Kachuri L, Jeon S, DeWan AT, Metayer C, Ma X, Witte JS, Chiang CWK, Wiemels JL, de Smith AJ. Genetic determinants of blood-cell traits influence susceptibility to childhood acute lymphoblastic leukemia. American Journal Of Human Genetics 2021, 108: 1823-1835. PMID: 34469753, PMCID: PMC8546033, DOI: 10.1016/j.ajhg.2021.08.004.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiomarkers, TumorBlood PlateletsCase-Control StudiesChildFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLymphocytesMaleMendelian Randomization AnalysisMiddle AgedMonocytesNeutrophilsPrecursor Cell Lymphoblastic Leukemia-LymphomaPrognosisProspective StudiesQuantitative Trait LociUnited KingdomConceptsTrait-associated variantsMulti-trait GWASBlood cell homeostasisWide association studyGenetic risk lociTrait variationHematologic traitsRisk lociAssociation studiesCell typesGenetic determinantsLociInfluence susceptibilityUK BiobankMendelian randomization analysisGWASEtiological relevanceRandomization analysisTraitsHomeostasisSusceptibilityAcute lymphoblastic leukemiaThe 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
Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome
Brown AL, de Smith AJ, Gant VU, Yang W, Scheurer ME, Walsh KM, Chernus JM, Kallsen NA, Peyton SA, Davies GE, Ehli EA, Winick N, Heerema NA, Carroll AJ, Borowitz MJ, Wood BL, Carroll WL, Raetz EA, Feingold E, Devidas M, Barcellos LF, Hansen HM, Morimoto L, Kang AY, Smirnov I, Healy J, Laverdière C, Sinnett D, Taub JW, Birch JM, Thompson P, Spector LG, Pombo-de-Oliveira MS, DeWan AT, Mullighan CG, Hunger SP, Pui CH, Loh ML, Zwick ME, Metayer C, Ma X, Mueller BA, Sherman SL, Wiemels JL, Relling MV, Yang JJ, Lupo PJ, Rabin KR. Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome. Blood 2019, 134: 1227-1237. PMID: 31350265, PMCID: PMC6788009, DOI: 10.1182/blood.2018890764.Peer-Reviewed Original ResearchMeSH KeywordsChildCyclin-Dependent Kinase Inhibitor p16DNA-Binding ProteinsDown SyndromeGATA3 Transcription FactorGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIkaros Transcription FactorPolymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaTranscription FactorsConceptsFirst genome-wide association studySusceptibility lociGenome-wide association studiesGenome-wide significanceFurther biological insightsGenetic variationEnhancer activityRisk lociBiological insightsLymphoblastoid cell linesAssociation studiesDifferential protein bindingFunctional significanceLociRisk allele frequenciesCell linesAllele frequenciesHigh penetranceRisk allelesProtein bindingCDKN2AGenetic susceptibilityHigher proliferationPenetranceAllele associationsHeritable variation at the chromosome 21 gene ERG is associated with acute lymphoblastic leukemia risk in children with and without Down syndrome
de Smith AJ, Walsh KM, Morimoto LM, Francis SS, Hansen HM, Jeon S, Gonseth S, Chen M, Sun H, Luna-Fineman S, Antillón F, Girón V, Kang AY, Smirnov I, Shao X, Whitehead TP, Barcellos LF, Jolly KW, Healy J, Laverdière C, Sinnett D, Taub JW, Birch JM, Thompson PD, Pombo-de-Oliveira MS, Spector LG, DeWan AT, Mueller BA, Chiang C, Metayer C, Ma X, Wiemels JL. Heritable variation at the chromosome 21 gene ERG is associated with acute lymphoblastic leukemia risk in children with and without Down syndrome. Leukemia 2019, 33: 2746-2751. PMID: 31296947, PMCID: PMC6858994, DOI: 10.1038/s41375-019-0514-9.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentCaliforniaCase-Control StudiesChildChild, PreschoolChromosomes, Human, Pair 21Down SyndromeFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGuatemalaHaplotypesHispanic or LatinoHumansInfantInfant, NewbornMalePolymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaPrincipal Component AnalysisRisk FactorsTranscriptional Regulator ERG
2018
BMI1 enhancer polymorphism underlies chromosome 10p12.31 association with childhood acute lymphoblastic leukemia
de Smith AJ, Walsh KM, Francis SS, Zhang C, Hansen HM, Smirnov I, Morimoto L, Whitehead TP, Kang A, Shao X, Barcellos LF, McKean‐Cowdin R, Zhang L, Fu C, Wang R, Yu H, Hoh J, Dewan AT, Metayer C, Ma X, Wiemels JL. BMI1 enhancer polymorphism underlies chromosome 10p12.31 association with childhood acute lymphoblastic leukemia. International Journal Of Cancer 2018, 143: 2647-2658. PMID: 29923177, PMCID: PMC6235695, DOI: 10.1002/ijc.31622.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultCaliforniaCell Cycle ProteinsChildChromosome MappingChromosomes, Human, Pair 10Core Binding Factor Alpha 1 SubunitEnhancer Elements, GeneticFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansK562 CellsLinkage DisequilibriumLogistic ModelsMalePhosphotransferases (Alcohol Group Acceptor)Polycomb Repressive Complex 1Polymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaTrans-ActivatorsYoung AdultConceptsFunctional variantsSingle nucleotide polymorphism (SNP) imputationGenome-wide significant associationGenome-wide association studiesStem cell enhancerPutative functional variantsChIP-seq dataRegion of associationGenetic Epidemiology ResearchChromosome 10p12Transcription factorsAdmixed AmericansCell enhancerLead SNPAssociation studiesSNP associationsAssociation analysisLinkage disequilibriumBMI1SNPsTight linkage disequilibriumPIP4K2APreferential bindingRisk allelesVariantsGWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21
Wiemels JL, Walsh KM, de Smith AJ, Metayer C, Gonseth S, Hansen HM, Francis SS, Ojha J, Smirnov I, Barcellos L, Xiao X, Morimoto L, McKean-Cowdin R, Wang R, Yu H, Hoh J, DeWan AT, Ma X. GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21. Nature Communications 2018, 9: 286. PMID: 29348612, PMCID: PMC5773513, DOI: 10.1038/s41467-017-02596-9.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentCaliforniaChild, PreschoolChromosomes, Human, Pair 17Chromosomes, Human, Pair 8FemaleGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyHispanic or LatinoHumansInfantInfant, NewbornMalePolymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaRisk FactorsConceptsNew risk lociRisk lociGenome-wide association studiesGrowth regulation pathwaysGenetic associationAcute lymphoblastic leukemiaNovel genetic associationsChildhood acute lymphoblastic leukemiaGenetic Epidemiology ResearchTranscription factorsStrong genetic associationGene expressionAssociation studiesLymphocyte developmentMYC oncogeneChromosome 17q12Oncology GroupLymphoblastic leukemiaLociChildren's Oncology GroupCalifornia Childhood Leukemia StudyChildhood Leukemia StudyStructural contactsYear of birthNon-Latino whites
2015
A Heritable Missense Polymorphism in CDKN2A Confers Strong Risk of Childhood Acute Lymphoblastic Leukemia and Is Preferentially Selected during Clonal Evolution
Walsh KM, de Smith AJ, Hansen HM, Smirnov IV, Gonseth S, Endicott AA, Xiao J, Rice T, Fu CH, McCoy LS, Lachance DH, Eckel-Passow JE, Wiencke JK, Jenkins RB, Wrensch MR, Ma X, Metayer C, Wiemels JL. A Heritable Missense Polymorphism in CDKN2A Confers Strong Risk of Childhood Acute Lymphoblastic Leukemia and Is Preferentially Selected during Clonal Evolution. Cancer Research 2015, 75: 4884-4894. PMID: 26527286, PMCID: PMC4651745, DOI: 10.1158/0008-5472.can-15-1105.Peer-Reviewed Original ResearchConceptsAcute lymphoblastic leukemiaChildhood acute lymphoblastic leukemiaLymphoblastic leukemiaCancer riskRisk allelesGeneral cancer riskPancreatic cancer riskGenome-wide association studiesCase-control populationCDKN2A variantsProtective allelesTumor growthClonal expansionChromosome 9p21.3Hispanic childrenMissense polymorphismStrong riskMissense variantsClonal evolutionRiskLeukemiaTumorsAllelic imbalanceEuropean ancestryPolymorphism
2014
Genomic ancestry and somatic alterations correlate with age at diagnosis in Hispanic children with B‐cell acute lymphoblastic leukemia
Walsh KM, de Smith A, Welch TC, Smirnov I, Cunningham MJ, Ma X, Chokkalingam AP, Dahl GV, Roberts W, Barcellos LF, Buffler PA, Metayer C, Wiemels JL. Genomic ancestry and somatic alterations correlate with age at diagnosis in Hispanic children with B‐cell acute lymphoblastic leukemia. American Journal Of Hematology 2014, 89: 721-725. PMID: 24753091, PMCID: PMC4069235, DOI: 10.1002/ajh.23727.Peer-Reviewed Original Research