2024
A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals
Jennings M, Martínez-Magaña J, Courchesne-Krak N, Cupertino R, Vilar-Ribó L, Bianchi S, Hatoum A, Atkinson E, Giusti-Rodriguez P, Montalvo-Ortiz J, Gelernter J, Artigas M, 23andMe I, Aslibekyan S, Auton A, Babalola E, Bell R, Bielenberg J, Bryc K, Bullis E, Coker D, Partida G, Dhamija D, Das S, Elson S, Eriksson N, Filshtein T, Fitch A, Fletez-Brant K, Fontanillas P, Freyman W, Granka J, Heilbron K, Hernandez A, Hicks B, Hinds D, Jewett E, Jiang Y, Kukar K, Kwong A, Lin K, Llamas B, Lowe M, McCreight J, McIntyre M, Micheletti S, Moreno M, Nandakumar P, Nguyen D, Noblin E, O'Connell J, Petrakovitz A, Poznik G, Reynoso A, Schumacher M, Shastri A, Shelton J, Shi J, Shringarpure S, Su Q, Tat S, Tchakouté C, Tran V, Tung J, Wang X, Wang W, Weldon C, Wilton P, Wong C, Elson S, Edenberg H, Fontanillas P, Palmer A, Sanchez-Roige S. A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals. EBioMedicine 2024, 103: 105086. PMID: 38580523, PMCID: PMC11121167, DOI: 10.1016/j.ebiom.2024.105086.Peer-Reviewed Original ResearchConceptsMultiple domains of healthDomains of healthEffects of alcohol consumptionAlcohol consumptionHealth outcomesPhenome-wide association studyAlcohol-related behaviorsCardio-metabolic healthPotential causal effectMendelian randomisation studiesGenome-wide association studiesPhenome-wide associationMR analysisPheWAS associationsMultiple domainsHypothesis-free approachPreventive medicineDiverse cohortPheWASAssociation studiesHealthReproductive healthAlcohol behaviorConsequences of drinkingEuropean cohort
2022
Genome-wide meta-analysis of alcohol use disorder in East Asians
Zhou H, Kalayasiri R, Sun Y, Nuñez YZ, Deng HW, Chen XD, Justice AC, Kranzler HR, Chang S, Lu L, Shi J, Sanichwankul K, Mutirangura A, Malison RT, Gelernter J. Genome-wide meta-analysis of alcohol use disorder in East Asians. Neuropsychopharmacology 2022, 47: 1791-1797. PMID: 35094024, PMCID: PMC9372033, DOI: 10.1038/s41386-022-01265-w.Peer-Reviewed Original ResearchConceptsAlcohol use disorderAlcohol dependenceUse disordersICD-9-CM diagnosisGenome-wide association studiesEast Asian subjectsElectronic health recordsPack yearsLeading causePolygenic risk scoresThai cohortRisk scoreAlcohol consumptionDSM-IVAsian subjectsCohortMillion Veteran Program sampleHealth recordsLarge genome-wide association studiesEast AsiansOngoing recruitmentRisk genesDisordersRisk lociSubjects
2021
The impact of removing former drinkers from genome‐wide association studies of AUDIT‐C
Dao C, Zhou H, Small A, Gordon KS, Li B, Kember RL, Ye Y, Gelernter J, Xu K, Kranzler HR, Zhao H, Justice AC. The impact of removing former drinkers from genome‐wide association studies of AUDIT‐C. Addiction 2021, 116: 3044-3054. PMID: 33861876, PMCID: PMC9377185, DOI: 10.1111/add.15511.Peer-Reviewed Original Research
2019
Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison
Sun Y, Chang S, Wang F, Sun H, Ni Z, Yue W, Zhou H, Gelernter J, Malison RT, Kalayasiri R, Wu P, Lu L, Shi J. Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison. Translational Psychiatry 2019, 9: 249. PMID: 31591379, PMCID: PMC6779867, DOI: 10.1038/s41398-019-0586-3.Peer-Reviewed Original ResearchAdultAlcohol DehydrogenaseAlcoholismAldehyde Dehydrogenase, MitochondrialAsian PeopleBlack or African AmericanCase-Control StudiesChinaCross-Cultural ComparisonGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLogistic ModelsMaleMiddle AgedMultifactorial InheritancePolymorphism, Single NucleotideWhite PeopleYoung AdultDifferentiating Types of Self-Reported Alcohol Abstinence
Gordon KS, McGinnis K, Dao C, Rentsch CT, Small A, Smith RV, Kember RL, Gelernter J, Kranzler HR, Bryant KJ, Tate JP, Justice AC. Differentiating Types of Self-Reported Alcohol Abstinence. AIDS And Behavior 2019, 24: 655-665. PMID: 31435887, PMCID: PMC6994373, DOI: 10.1007/s10461-019-02638-x.Peer-Reviewed Original ResearchConceptsLifetime abstainersSelf-reported alcohol abstinenceAlcohol biomarkersGenetic polymorphismsLogistic regression modelsHepatitis CAlcohol abstinenceUninfected individualsCharacteristics of peopleAlcohol useAbstinenceHealth effectsSmokingAbstainersBiomarkersRegression modelsOddsAssociationPLWHPolymorphismHIVCocaineGenetics of Alcoholism
Edenberg HJ, Gelernter J, Agrawal A. Genetics of Alcoholism. Current Psychiatry Reports 2019, 21: 26. PMID: 30852706, DOI: 10.1007/s11920-019-1008-1.Peer-Reviewed Original ResearchMeSH KeywordsAlcohol DehydrogenaseAlcohol DrinkingAlcoholismAldehyde Dehydrogenase, MitochondrialHumansConceptsEuropean ancestry populations
2018
AUDIT‐C and ICD codes as phenotypes for harmful alcohol use: association with ADH1B polymorphisms in two US populations
Justice AC, Smith RV, Tate JP, McGinnis K, Xu K, Becker WC, Lee K, Lynch K, Sun N, Concato J, Fiellin DA, Zhao H, Gelernter J, Kranzler HR, Program O. AUDIT‐C and ICD codes as phenotypes for harmful alcohol use: association with ADH1B polymorphisms in two US populations. Addiction 2018, 113: 2214-2224. PMID: 29972609, PMCID: PMC6226338, DOI: 10.1111/add.14374.Peer-Reviewed Original Research
2017
Validating Harmful Alcohol Use as a Phenotype for Genetic Discovery Using Phosphatidylethanol and a Polymorphism in ADH1B
Justice AC, McGinnis KA, Tate JP, Xu K, Becker WC, Zhao H, Gelernter J, Kranzler HR. Validating Harmful Alcohol Use as a Phenotype for Genetic Discovery Using Phosphatidylethanol and a Polymorphism in ADH1B. Alcohol Clinical And Experimental Research 2017, 41: 998-1003. PMID: 28295416, PMCID: PMC5501250, DOI: 10.1111/acer.13373.Peer-Reviewed Original ResearchMeSH KeywordsAlcohol DehydrogenaseAlcohol-Related DisordersCohort StudiesFemaleGlycerophospholipidsHumansLongitudinal StudiesMalePhenotypePolymorphism, GeneticVeteransConceptsHarmful alcohol useAlcohol exposureAlcohol useElectronic health record dataEHR dataAUDIT-C scoresHealth record dataLongitudinal electronic health record dataLongitudinal trajectoriesChi-square testEHR-derived phenotypesStudy cohortBlood drawCommon missense polymorphismGenetic risk variantsBlood samplingMissense polymorphismAlcohol riskQuantitative biomarkersRecord dataMedianRisk variantsOverall sampleAfrican AmericansADH1B geneADH1B: From alcoholism, natural selection, and cancer to the human phenome
Polimanti R, Gelernter J. ADH1B: From alcoholism, natural selection, and cancer to the human phenome. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2017, 177: 113-125. PMID: 28349588, PMCID: PMC5617762, DOI: 10.1002/ajmg.b.32523.Peer-Reviewed Original ResearchConceptsHuman phenomeMultiple human tissuesPhenome-wide association studyMolecular functionsGene regulationPhenotypic traitsBioinformatics analysisEvolutionary dataFunctional allelesAssociation studiesMetabolic traitsAlcohol metabolismMolecular pathwaysMultiple molecular pathwaysHuman evolutionPhenomeGenesADH1B geneTraitsComplex mechanismsHuman tissuesMetabolismAllelesADH1BADH1B locus
2016
Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women
Polimanti R, Kranzler HR, Gelernter J. Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women. Neuropsychopharmacology 2016, 41: 2688-2696. PMID: 27187070, PMCID: PMC5026736, DOI: 10.1038/npp.2016.72.Peer-Reviewed Original ResearchConceptsHealth initiativesRisk allelesSocioeconomic statusPhenome-wide association studyWomen's Health InitiativeMetabolism-related mechanismsMedication useLung cancerTobacco useDietary habitsSmoking behaviorNicotine useReproductive historyReproductive healthSuggestive findingsAlcohol useAnthropometric characteristicsMental healthHealth conditionsMetabolic conditionsCausative relationshipAssociation studiesDrinking behaviorADH1BAssociation
2015
Genomewide Association Study for Maximum Number of Alcoholic Drinks in European Americans and African Americans
Xu K, Kranzler HR, Sherva R, Sartor CE, Almasy L, Koesterer R, Zhao H, Farrer LA, Gelernter J. Genomewide Association Study for Maximum Number of Alcoholic Drinks in European Americans and African Americans. Alcohol Clinical And Experimental Research 2015, 39: 1137-1147. PMID: 26036284, PMCID: PMC4706077, DOI: 10.1111/acer.12751.Peer-Reviewed Original ResearchWhich alcohol use disorder criteria contribute to the association of ADH1B with alcohol dependence?
Hart AB, Lynch KG, Farrer L, Gelernter J, Kranzler HR. Which alcohol use disorder criteria contribute to the association of ADH1B with alcohol dependence? Addiction Biology 2015, 21: 924-938. PMID: 25828809, PMCID: PMC4591076, DOI: 10.1111/adb.12244.Peer-Reviewed Original Research
2014
The Joint Effects of ADH1B Variants and Childhood Adversity on Alcohol Related Phenotypes in African‐American and European‐American Women and Men
Sartor CE, Wang Z, Xu K, Kranzler HR, Gelernter J. The Joint Effects of ADH1B Variants and Childhood Adversity on Alcohol Related Phenotypes in African‐American and European‐American Women and Men. Alcohol Clinical And Experimental Research 2014, 38: 2907-2914. PMID: 25410943, PMCID: PMC4445128, DOI: 10.1111/acer.12572.Peer-Reviewed Original ResearchConceptsChildhood adversityAllele carriersEA menAlcohol use disorder symptomsAlcohol phenotypesRisk factorsAA womenProtective effectADH1B rs1229984Psychiatric outcomesEA womenEuropean American womenOrdinal regression analysisProtective allelesAlcohol dependenceAUD symptomsSubstance dependenceSingle nucleotide polymorphismsDisorder symptomsADH1B variantsAlcohol problemsWomenMenRegression analysisSignificant main effectAlcohol consumption mediates the relationship between ADH1B and DSM-IV alcohol use disorder and criteria.
Kilcoyne B, Shmulewitz D, Meyers JL, Aharonovich E, Greenstein E, Frisch A, Weizman A, Spivak B, Edenberg HJ, Gelernter J, Hasin DS. Alcohol consumption mediates the relationship between ADH1B and DSM-IV alcohol use disorder and criteria. Journal Of Studies On Alcohol And Drugs 2014, 75: 635-42. PMID: 24988262, PMCID: PMC4108604, DOI: 10.15288/jsad.2014.75.635.Peer-Reviewed Original Research
2013
Genome-wide association study of alcohol dependence:significant findings in African- and European-Americans including novel risk loci
Gelernter J, Kranzler HR, Sherva R, Almasy L, Koesterer R, Smith AH, Anton R, Preuss UW, Ridinger M, Rujescu D, Wodarz N, Zill P, Zhao H, Farrer LA. Genome-wide association study of alcohol dependence:significant findings in African- and European-Americans including novel risk loci. Molecular Psychiatry 2013, 19: 41-49. PMID: 24166409, PMCID: PMC4165335, DOI: 10.1038/mp.2013.145.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAlcohol DehydrogenaseAlcoholismAminopeptidasesBlack or African AmericanChromosome MappingCohort StudiesEukaryotic Initiation FactorsFemaleFollow-Up StudiesGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansLIM Domain ProteinsMaleMicrofilament ProteinsMitochondrial ProteinsPolymorphism, Single NucleotidePsychiatric Status Rating ScalesUnited StatesVesicular Transport ProteinsWhite PeopleConceptsRisk lociGWS associationsGenome-wide significant associationGenome-wide association studiesADH gene clusterSchizophrenia risk lociNovel risk lociGene expression evidenceGene clusterExpression evidenceLocus mappingNovel lociAD GWASBiological convergenceChromosome 4Chromosome 5Same locusAD risk lociAssociation studiesEnzyme genesRisk genesLociPsychiatric traitsGenesNovel associationsChildhood adversity moderates the effect of ADH1B on risk for alcohol‐related phenotypes in Jewish Israeli drinkers
Meyers JL, Shmulewitz D, Wall MM, Keyes KM, Aharonovich E, Spivak B, Weizman A, Frisch A, Edenberg HJ, Gelernter J, Grant BF, Hasin D. Childhood adversity moderates the effect of ADH1B on risk for alcohol‐related phenotypes in Jewish Israeli drinkers. Addiction Biology 2013, 20: 205-214. PMID: 24164917, PMCID: PMC3999313, DOI: 10.1111/adb.12102.Peer-Reviewed Original ResearchConceptsADH1B rs1229984Childhood adversityAUD severityAlcohol consumptionHeavy alcohol consumptionEnvironmental risk factorsAdult household residentsEarly life adversityMaximum drinksAUD symptom severityRisk factorsAlcohol metabolismSymptom severityLife adversityAlcohol-related phenotypesSeverityDisorder severityGenetic vulnerabilityAlcohol‐Metabolizing Genes and Alcohol Phenotypes in an Israeli Household Sample
Meyers JL, Shmulewitz D, Aharonovich E, Waxman R, Frisch A, Weizman A, Spivak B, Edenberg HJ, Gelernter J, Hasin DS. Alcohol‐Metabolizing Genes and Alcohol Phenotypes in an Israeli Household Sample. Alcohol Clinical And Experimental Research 2013, 37: 1872-1881. PMID: 23895337, PMCID: PMC3812252, DOI: 10.1111/acer.12176.Peer-Reviewed Original Research
2012
Further clarification of the contribution of the ADH1C gene to vulnerability of alcoholism and selected liver diseases
Li D, Zhao H, Gelernter J. Further clarification of the contribution of the ADH1C gene to vulnerability of alcoholism and selected liver diseases. Human Genetics 2012, 131: 1361-1374. PMID: 22476623, PMCID: PMC3557796, DOI: 10.1007/s00439-012-1163-5.Peer-Reviewed Original Research
2011
Strong Association of the Alcohol Dehydrogenase 1B Gene (ADH1B) with Alcohol Dependence and Alcohol-Induced Medical Diseases
Li D, Zhao H, Gelernter J. Strong Association of the Alcohol Dehydrogenase 1B Gene (ADH1B) with Alcohol Dependence and Alcohol-Induced Medical Diseases. Biological Psychiatry 2011, 70: 504-512. PMID: 21497796, PMCID: PMC3142297, DOI: 10.1016/j.biopsych.2011.02.024.Peer-Reviewed Original ResearchMeSH KeywordsAlcohol DehydrogenaseAlcohol-Induced DisordersAlcoholismEthnicityGenetic Association StudiesGenetic Predisposition to DiseaseHumansConceptsAlcohol dependenceAlcohol dehydrogenase 1B (ADH1B) geneMedical diseasesAlcohol-induced liver diseaseStrong associationCertain Asian populationsRandom-effects modelADH1B geneLarger ORsLiver diseaseSubgroup analysisLarger sample sizeDrug dependenceSignificant associationSubstance dependenceMultiple ethnic populationsRecessive modelAsian populationsDisease
2010
ADH1A variation predisposes to personality traits and substance dependence
Zuo L, Gelernter J, Kranzler HR, Stein MB, Zhang H, Wei F, Sen S, Poling J, Luo X. ADH1A variation predisposes to personality traits and substance dependence. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2010, 153B: 376-386. PMID: 19526455, PMCID: PMC2861415, DOI: 10.1002/ajmg.b.30990.Peer-Reviewed Original Research