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
Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome‐wide association study
Wang Z, Budhu AS, Shen Y, Wong LL, Hernandez BY, Tiirikainen M, Ma X, Irwin ML, Lu L, Zhao H, Lim JK, Taddei T, Mishra L, Pawlish K, Stroup A, Brown R, Nguyen MH, Koshiol J, Hernandez MO, Forgues M, Yang H, Lee M, Huang Y, Iwasaki M, Goto A, Suzuki S, Matsuda K, Tanikawa C, Kamatani Y, Mann D, Guarnera M, Shetty K, Thomas CE, Yuan J, Khor CC, Koh W, Risch H, Wang XW, Yu H. Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome‐wide association study. JGH Open 2021, 5: 1363-1372. PMID: 34950780, PMCID: PMC8674550, DOI: 10.1002/jgh3.12682.Peer-Reviewed Original ResearchNonalcoholic fatty liver diseaseCase-control studyHepatocellular carcinomaSingle nucleotide polymorphismsChronic hepatitis C virus (HCV) infectionHepatitis C virus infectionGenetic susceptibilityC virus infectionLong-term alcohol useFatty liver diseaseUS case-control studyBody mass indexMajor risk factorGenome-wide association studiesHCV infectionCohort studyLiver diseaseCigarette smokingMass indexRisk factorsHCC casesVirus infectionGene-environment interactionsUS populationDisease riskEpigenome-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 cells
2020
Genetic Determinants of Blood Cell Traits Play a Role in Susceptibility to Acute Lymphoblastic Leukemia
Kachuri L, Jeon S, DeWan A, Metayer C, Witte J, Ma X, Chiang C, Wiemels J, de Smith A. Genetic Determinants of Blood Cell Traits Play a Role in Susceptibility to Acute Lymphoblastic Leukemia. Blood 2020, 136: 10-11. DOI: 10.1182/blood-2020-141443.Peer-Reviewed Original ResearchGenome-wide association studiesBlood cell traitsLD score regressionTrait variationTwo-stage genome-wide association studyGenome-wide single nucleotide polymorphism (SNP) dataGenome-wide SNP dataTrait-specific lociScore regressionSingle nucleotide polymorphism dataNucleotide polymorphism dataLikely causal variantsEuropean ancestryCell type ratiosEuropean ancestry individualsMulti-trait analysisUK BiobankGenetic variationPolymorphism dataGenetic basisSNP dataCausal variantsPutative novelRisk lociGenetic level
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 associations
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