2024
Application of polygenic scores to a deeply phenotyped sample enriched for substance use disorders reveals extensive pleiotropy with psychiatric and somatic traits
Hartwell E, Jinwala Z, Milone J, Ramirez S, Gelernter J, Kranzler H, Kember R. Application of polygenic scores to a deeply phenotyped sample enriched for substance use disorders reveals extensive pleiotropy with psychiatric and somatic traits. Neuropsychopharmacology 2024, 49: 1958-1967. PMID: 39043921, PMCID: PMC11480112, DOI: 10.1038/s41386-024-01922-2.Peer-Reviewed Original ResearchSubstance use disordersPost-traumatic stress disorderGeneralized anxiety disorderGenetic liabilityPolygenic scoresBipolar disorderSubstance use phenotypesSomatic traitsBody mass indexSubstance use categoriesEffect of genetic liabilityAnxiety disordersDepression-relatedDepressive disorderApplication of polygenic scoresStress disorderPsychiatric disordersPsychiatric phenotypesUse disorderPhenome-wide association studyGenetic influencesCross-sectional sampleMedical illnessPrecision medicine effortsPhenotyped sampleDistinguishing vulnerability and resilience to posttraumatic stress disorder evaluating traumatic experiences, genetic risk and electronic health records
Løkhammer S, Koller D, Wendt F, Choi K, He J, Friligkou E, Overstreet C, Gelernter J, Hellard S, Polimanti R. Distinguishing vulnerability and resilience to posttraumatic stress disorder evaluating traumatic experiences, genetic risk and electronic health records. Psychiatry Research 2024, 337: 115950. PMID: 38744179, PMCID: PMC11156529, DOI: 10.1016/j.psychres.2024.115950.Peer-Reviewed Original ResearchElectronic health recordsPosttraumatic stress disorderHealth recordsPTSD vulnerabilityUK Biobank (UKBPhenome-wide association studyRisk scorePhenotype risk scoreUs Research ProgramPolygenic risk scoresStress disorderAoU participantsUKB participantsPresence of posttraumatic stress disorderTrauma burdenGenetic riskPosttraumatic stress disorder symptomsAssociation studiesPheWASClinical comorbiditiesComorbid associationsEye conditionsAOUInverse relationshipMultiple phenotypesA 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
2023
MULTI-ANCESTRY PHENOME-WIDE ASSOCIATION ANALYSES OF GENETIC LIABILITY FOR PROBLEMATIC ALCOHOL USE
Kember R, Johnson J, Johnston K, Lee H, Xu J, Davis L, Smoller J, Mallard T, Huckins L, Sanchez-Roige S, Kranzler H, Gelernter J, Zhou H. MULTI-ANCESTRY PHENOME-WIDE ASSOCIATION ANALYSES OF GENETIC LIABILITY FOR PROBLEMATIC ALCOHOL USE. European Neuropsychopharmacology 2023, 75: s10. DOI: 10.1016/j.euroneuro.2023.08.027.Peer-Reviewed Original Research
2022
Phenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample
Kember RL, Hartwell EE, Xu H, Rotenberg J, Almasy L, Zhou H, Gelernter J, Kranzler HR. Phenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample. Biological Psychiatry 2022, 93: 536-545. PMID: 36273948, PMCID: PMC9931661, DOI: 10.1016/j.biopsych.2022.08.010.Peer-Reviewed Original ResearchConceptsSubstance use disordersAlcohol use disorderOpioid use disorderPolygenic risk scoresUse disordersCo-occurring psychiatric disordersComprehensive psychiatric interviewSemi-Structured AssessmentElectronic health recordsControl subjectsLow prevalencePsychiatric interviewRisk scorePsychiatric disordersPhenome-wide association analysisDrug dependenceEuropean individualsHealth recordsLifetime cannabisPhenome-wide association studyDisordersAfrican ancestry individualsDSM diagnosesPopulation sampleGenetic liability
2017
Phenome-wide association study for CYP2A6 alleles: rs113288603 is associated with hearing loss symptoms in elderly smokers
Polimanti R, Jensen KP, Gelernter J. Phenome-wide association study for CYP2A6 alleles: rs113288603 is associated with hearing loss symptoms in elderly smokers. Scientific Reports 2017, 7: 1034. PMID: 28432340, PMCID: PMC5430682, DOI: 10.1038/s41598-017-01098-4.Peer-Reviewed Original ResearchConceptsLoss symptomsElderly subjectsAge-related hearing lossPhenome-wide association studyElderly smokersCigarette smokingNovel phenotypic associationsCerebellar hemisphereAuditory functionDiscovery cohortHearing lossReplication cohortBrain regionsSignificant associationNicotine metabolismCYP2A6 expressionCYP2A6 allelesMember 6Association studiesSmokingCohortSymptomsAssociationRegulatory roleInvolvementADH1B: 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