Featured Publications
Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits
Zhou H, Sealock JM, Sanchez-Roige S, Clarke TK, Levey DF, Cheng Z, Li B, Polimanti R, Kember RL, Smith RV, Thygesen JH, Morgan MY, Atkinson SR, Thursz MR, Nyegaard M, Mattheisen M, Børglum AD, Johnson EC, Justice AC, Palmer AA, McQuillin A, Davis LK, Edenberg HJ, Agrawal A, Kranzler HR, Gelernter J. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nature Neuroscience 2020, 23: 809-818. PMID: 32451486, PMCID: PMC7485556, DOI: 10.1038/s41593-020-0643-5.Peer-Reviewed Original ResearchConceptsRegulatory genomic regionsGenome-wide association studiesNovel risk lociEuropean ancestry individualsPolygenic risk score analysisIndependent risk variantsGenetic architectureGenomic regionsRisk lociAssociation studiesGenetic relationshipsRisk genesGenetic correlationsPsychiatric traitsRisk variantsRisk score analysisTraitsGenetic heritabilityYields insightsBiobank samplesMendelian randomizationGenesLociBiologyHeritability
2024
Gene × environment effects and mediation involving adverse childhood events, mood and anxiety disorders, and substance dependence
Kranzler H, Davis C, Feinn R, Jinwala Z, Khan Y, Oikonomou A, Silva-Lopez D, Burton I, Dixon M, Milone J, Ramirez S, Shifman N, Levey D, Gelernter J, Hartwell E, Kember R. Gene × environment effects and mediation involving adverse childhood events, mood and anxiety disorders, and substance dependence. Nature Human Behaviour 2024, 8: 1616-1627. PMID: 38834750, DOI: 10.1038/s41562-024-01885-w.Peer-Reviewed Original ResearchAdverse childhood eventsSubstance dependenceMood/anxiety disordersAnxiety disordersChildhood eventsIndirect associationsGenetic riskExposure to adverse childhood eventsDevelopment of moodSubstance use disordersAssociations of adverse childhood eventsUse disorderMediation modelMood/anxietyDisorder factorsPolygenic scoresIndirect pathsDisordersEuropean ancestry individualsMoodTreatment approachesAnxietySelf-medicationEuropean ancestryLatent variables
2023
Identifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study
Xu H, Toikumo S, Crist R, Glogowska K, Jinwala Z, Deak J, Justice A, Gelernter J, Johnson E, Kranzler H, Kember R. Identifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study. Addiction 2023, 118: 1942-1952. PMID: 37156939, PMCID: PMC10754226, DOI: 10.1111/add.16229.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSignificant single nucleotide polymorphismsSubstance use traitsMulti-trait analysisAssociation studiesGenetic architectureUse traitsGenome-wide significant single nucleotide polymorphismsProtein-protein interaction analysisTrait genetic architectureNumber of lociPolygenic risk scoresEuropean ancestry individualsNovel lociSingle nucleotide polymorphismsGenetic lociGWAS studiesLociMultiple related phenotypesNucleotide polymorphismsRelated phenotypesTraitsNovel associationsMTAgBiobank samplesDoes polygenic risk for substance‐related traits predict ages of onset and progression of symptoms?
Kranzler H, Feinn R, Xu H, Ho B, Saini D, Nicastro O, Jacoby A, Toikumo S, Gelernter J, Hartwell E, Kember R. Does polygenic risk for substance‐related traits predict ages of onset and progression of symptoms? Addiction 2023, 118: 1675-1686. PMID: 37069489, PMCID: PMC10525011, DOI: 10.1111/add.16210.Peer-Reviewed Original ResearchConceptsOpioid use disorderSubstance use disordersProgression of symptomsPolygenic risk scoresAlcohol use disorderUse disordersAfrican ancestry individualsGenetic riskRegular useEuropean ancestry individualsEarly onsetMore rapid progressionRegular alcohol useShorter progression timeAge of onsetFirst substance useDiscovery sampleUS inpatientsOnset of problemsOutpatient settingDisease progressionRapid progressionSymptom progressionRisk scoreGenome-wide association studies
2022
Integrating human brain proteomic data with genome-wide association study findings identifies novel brain proteins in substance use traits
Toikumo S, Xu H, Gelernter J, Kember RL, Kranzler HR. Integrating human brain proteomic data with genome-wide association study findings identifies novel brain proteins in substance use traits. Neuropsychopharmacology 2022, 47: 2292-2299. PMID: 35941285, PMCID: PMC9630289, DOI: 10.1038/s41386-022-01406-1.Peer-Reviewed Original ResearchConceptsSubstance use traitsProteome-wide association studyUse traitsProtein abundanceAssociation studiesBrain protein abundanceWide association studyGenome-wide association study summary statisticsHuman brain proteomeFine-mapping analysisGenetic risk lociBrain transcriptomic dataEuropean ancestry individualsOpioid use disorderProteomic abundanceTranscriptomic levelTranscriptomic dataAlcohol use disorderProteomic dataBrain proteomeGenetic lociTranscript levelsRisk lociGene expressionSignificant genes