2021
Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality
Polimanti R, Levey DF, Pathak GA, Wendt FR, Nunez YZ, Ursano RJ, Kessler RC, Kranzler HR, Stein MB, Gelernter J. Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality. Translational Psychiatry 2021, 11: 34. PMID: 33431810, PMCID: PMC7801457, DOI: 10.1038/s41398-020-01153-1.Peer-Reviewed Original ResearchMeSH KeywordsBayes TheoremChromosomal Proteins, Non-HistoneGene-Environment InteractionHumansRisk AssessmentRisk FactorsSuicidal IdeationSuicideTobacco Use DisorderConceptsSuicidal ideationPolysubstance dependenceSuicide attemptsOdds ratioGene-environment interactionsYale-PennMultivariate logistic regressionImportant risk factorMultivariate gene-environment interactionsMental health risksOpioid dependenceRisk factorsNicotine dependenceSuicidality outcomesCocaine dependenceLogistic regressionSubstance dependenceSuicidalityCohortLifetime suicidalityLinear mixed modelsMultiple substancesArmy STARRSArmy personnelHealth risks
2020
A genome-wide association study of cocaine use disorder accounting for phenotypic heterogeneity and gene–environment interaction
Sun J, Kranzler HR, Gelernter J, Bi J. A genome-wide association study of cocaine use disorder accounting for phenotypic heterogeneity and gene–environment interaction. Journal Of Psychiatry And Neuroscience 2020, 45: 34-44. PMID: 31490055, PMCID: PMC6919916, DOI: 10.1503/jpn.180098.Peer-Reviewed Original ResearchConceptsGenetic lociGenome-wide association testsPhenotypic heterogeneityNew genetic lociGenetic variantsWide association studyGene-environment interplayNovel genetic variantsHigh heritability estimatesSignificant genomeReplication sampleSingle nucleotide polymorphismsGenetic variationAssociation studiesLociNucleotide polymorphismsAssociation TestHeritability estimatesGene-environment interactionsReplication resultsCluster analysisEnvironmental factorsTRAK2GenomeDiscovery phase
2018
Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls
Pettersson E, Lichtenstein P, Larsson H, Song J, Agrawal A, Børglum A, Bulik C, Daly M, Davis L, Demontis D, Edenberg H, Grove J, Gelernter J, Neale B, Pardiñas A, Stahl E, Walters J, Walters R, Sullivan P, Posthuma D, Polderman T. Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls. Psychological Medicine 2018, 49: 1166-1173. PMID: 30221610, PMCID: PMC6421104, DOI: 10.1017/s0033291718002039.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismAnorexia NervosaAttention Deficit Disorder with HyperactivityAutism Spectrum DisorderBipolar DisorderCase-Control StudiesCohort StudiesDepressive Disorder, MajorFamilyFemaleGene-Environment InteractionGenotypeHumansMaleMental DisordersObsessive-Compulsive DisorderQuantitative Trait, HeritableSchizophreniaSchizophrenic PsychologySiblingsSweden
2017
Oxytocin receptor gene polymorphisms, attachment, and PTSD: Results from the National Health and Resilience in Veterans Study
Sippel LM, Han S, Watkins LE, Harpaz-Rotem I, Southwick SM, Krystal JH, Olff M, Sherva R, Farrer LA, Kranzler HR, Gelernter J, Pietrzak RH. Oxytocin receptor gene polymorphisms, attachment, and PTSD: Results from the National Health and Resilience in Veterans Study. Journal Of Psychiatric Research 2017, 94: 139-147. PMID: 28715704, PMCID: PMC5605420, DOI: 10.1016/j.jpsychires.2017.07.008.Peer-Reviewed Original ResearchS100A10 identified in a genome-wide gene × cannabis dependence interaction analysis of risky sexual behaviours
Polimanti R, Meda SA, Pearlson GD, Zhao H, Sherva R, Farrer LA, Kranzler HR, Gelernter J. S100A10 identified in a genome-wide gene × cannabis dependence interaction analysis of risky sexual behaviours. Journal Of Psychiatry And Neuroscience 2017, 42: 252-261. PMID: 28418321, PMCID: PMC5487272, DOI: 10.1503/jpn.160189.Peer-Reviewed Original ResearchConceptsRisky sexual behaviorCAD diagnosisLow-frequency fluctuation (ALFF) analysisMultiple sexual partnersLeft paracentral lobuleSexual behaviorAfrican American cohortSemi-Structured AssessmentALFF analysisSexual functionAfrican American participantsCalcium-binding proteinsParacentral lobuleIndependent cohortRight pallidumCalcium homeostasisUnprotected sexCannabis dependenceDrug dependenceSignificant associationBrain regionsSexual partnersFrequency fluctuation analysisPrevious genome-wide association studyCohortA genome-wide gene-by-trauma interaction study of alcohol misuse in two independent cohorts identifies PRKG1 as a risk locus
Polimanti R, Kaufman J, Zhao H, Kranzler HR, Ursano RJ, Kessler RC, Gelernter J, Stein MB. A genome-wide gene-by-trauma interaction study of alcohol misuse in two independent cohorts identifies PRKG1 as a risk locus. Molecular Psychiatry 2017, 23: 154-160. PMID: 28265120, PMCID: PMC5589475, DOI: 10.1038/mp.2017.24.Peer-Reviewed Original ResearchConceptsGenome-wide interaction studyGene Ontology (GO) enrichment analysisOntology enrichment analysisProtein kinase 1Protein regulationSame effect directionCyclic GMP-dependent protein kinase 1Circadian rhythm regulationRisk lociWide geneEnrichment analysisInteraction studiesKinase 1Individual genetic riskPsychiatric geneticsCalcium-activated potassium channelsGenesLociPRKG1Potassium channelsEffect directionRhythm regulationAlcohol use problemsRegulationAlcohol misuse
2016
Genetic factor common to schizophrenia and HIV infection is associated with risky sexual behavior: antagonistic vs. synergistic pleiotropic SNPs enriched for distinctly different biological functions
Wang Q, Polimanti R, Kranzler HR, Farrer LA, Zhao H, Gelernter J. Genetic factor common to schizophrenia and HIV infection is associated with risky sexual behavior: antagonistic vs. synergistic pleiotropic SNPs enriched for distinctly different biological functions. Human Genetics 2016, 136: 75-83. PMID: 27752767, PMCID: PMC5215962, DOI: 10.1007/s00439-016-1737-8.Peer-Reviewed Original Research
2015
Dissecting ancestry genomic background in substance dependence genome-wide association studies
Polimanti R, Yang C, Zhao H, Gelernter J. Dissecting ancestry genomic background in substance dependence genome-wide association studies. Pharmacogenomics 2015, 16: 1487-1498. PMID: 26267224, PMCID: PMC4632979, DOI: 10.2217/pgs.15.91.Peer-Reviewed Original ResearchMeSH KeywordsAlcoholismAlgorithmsAllelesBlack or African AmericanGene FrequencyGene-Environment InteractionGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyHaplotypesHumansMolecular Sequence AnnotationOpioid-Related DisordersSubstance-Related DisordersTobacco Use DisorderWhite PeopleConceptsGenome-wide association studiesGenomic backgroundFunctional allelesAssociation studiesCommon functional allelesWide association studyLocal haplotype structureGenetic lociSD traitHaplotype structureRelevant genesGenesLociInteractive partnersPopulation diversityHigh frequency differencesAllelesFrequency differenceGenomeTraitsDiversityRoleVariants
2014
Genetics of Complex Traits in Psychiatry
Gelernter J. Genetics of Complex Traits in Psychiatry. Biological Psychiatry 2014, 77: 36-42. PMID: 25444161, PMCID: PMC4282183, DOI: 10.1016/j.biopsych.2014.08.005.Peer-Reviewed Original ResearchConceptsComplex traitsNext-generation high-throughput sequencingGenome-wide association studiesHigh-throughput sequencingSingle nucleotide polymorphismsEpigenetic effectsRisk allelesAssociation studiesExpression dataMultiple risk allelesPsychiatric geneticsPsychiatric traitsNumber variantsNucleotide polymorphismsTraitsGeneticsNew mutationsTrait riskAllelesEpistasisMinor effectMethylationKind of variationVariantsSequencing
2013
Childhood 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 vulnerability
2012
Examining the relation between the serotonin transporter 5-HTTPLR genotype x trauma exposure interaction on a contemporary phenotypic model of posttraumatic stress symptomatology: A pilot study
Pietrzak RH, Galea S, Southwick SM, Gelernter J. Examining the relation between the serotonin transporter 5-HTTPLR genotype x trauma exposure interaction on a contemporary phenotypic model of posttraumatic stress symptomatology: A pilot study. Journal Of Affective Disorders 2012, 148: 123-128. PMID: 23183127, PMCID: PMC3604029, DOI: 10.1016/j.jad.2012.11.003.Peer-Reviewed Original ResearchAdolescentAdultAgedAged, 80 and overCyclonic StormsDisastersFemaleGene-Environment InteractionGenetic Predisposition to DiseaseGenotypeHumansMaleMiddle AgedModels, GeneticPhenotypePilot ProjectsPolymorphism, GeneticQualitative ResearchSerotonin Plasma Membrane Transport ProteinsStress Disorders, Post-TraumaticYoung AdultIncreased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset Smokers
Hartz SM, Short SE, Saccone NL, Culverhouse R, Chen L, Schwantes-An TH, Coon H, Han Y, Stephens SH, Sun J, Chen X, Ducci F, Dueker N, Franceschini N, Frank J, Geller F, Gubjartsson D, Hansel NN, Jiang C, Keskitalo-Vuokko K, Liu Z, Lyytikäinen LP, Michel M, Rawal R, Rosenberger A, Scheet P, Shaffer JR, Teumer A, Thompson JR, Vink JM, Vogelzangs N, Wenzlaff AS, Wheeler W, Xiao X, Yang BZ, Aggen SH, Balmforth AJ, Baumeister SE, Beaty T, Bennett S, Bergen AW, Boyd HA, Broms U, Campbell H, Chatterjee N, Chen J, Cheng YC, Cichon S, Couper D, Cucca F, Dick DM, Foroud T, Furberg H, Giegling I, Gu F, Hall AS, Hällfors J, Han S, Hartmann AM, Hayward C, Heikkilä K, Hewitt JK, Hottenga JJ, Jensen MK, Jousilahti P, Kaakinen M, Kittner SJ, Konte B, Korhonen T, Landi MT, Laatikainen T, Leppert M, Levy SM, Mathias RA, McNeil DW, Medland SE, Montgomery GW, Muley T, Murray T, Nauck M, North K, Pergadia M, Polasek O, Ramos EM, Ripatti S, Risch A, Ruczinski I, Rudan I, Salomaa V, Schlessinger D, Styrkársdóttir U, Terracciano A, Uda M, Willemsen G, Wu X, Abecasis G, Barnes K, Bickeböller H, Boerwinkle E, Boomsma DI, Caporaso N, Duan J, Edenberg HJ, Francks C, Gejman PV, Gelernter J, Grabe HJ, Hops H, Jarvelin MR, Viikari J, Kähönen M, Kendler KS, Lehtimäki T, Levinson DF, Marazita ML, Marchini J, Melbye M, Mitchell BD, Murray JC, Nöthen MM, Penninx BW, Raitakari O, Rietschel M, Rujescu D, Samani NJ, Sanders AR, Schwartz AG, Shete S, Shi J, Spitz M, Stefansson K, Swan GE, Thorgeirsson T, Völzke H, Wei Q, Wichmann H, Amos CI, Breslau N, Cannon DS, Ehringer M, Grucza R, Hatsukami D, Heath A, Johnson EO, Kaprio J, Madden P, Martin NG, Stevens VL, Stitzel JA, Weiss RB, Kraft P, Bierut LJ. Increased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset Smokers. JAMA Psychiatry 2012, 69: 854-860. PMID: 22868939, PMCID: PMC3482121, DOI: 10.1001/archgenpsychiatry.2012.124.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdolescent DevelopmentAdultAge of OnsetEuropeFemaleGene-Environment InteractionGenetic Association StudiesGenetic Predisposition to DiseaseHumansMaleNerve Tissue ProteinsNicotinePolymorphism, Single NucleotideReceptors, NicotinicSeverity of Illness IndexSmokingTobacco Use DisorderConceptsEarly-onset smokersLate-onset smokersHeavy smokersRisk allelesGenetic vulnerabilityRs16969968 genotypeLight smokersLight smokingRegular smokingSmokersSmokingMeta-AnalysisLogistic regressionRs16969968Single nucleotide polymorphismsAgeNonsynonymous single nucleotide polymorphismsCHRNA5Recent studiesAvailable genetic studiesAssociationSample sizeStudyCigarettesGenetic studies
2011
Childhood Adversity Increases Risk for Nicotine Dependence and Interacts with α5 Nicotinic Acetylcholine Receptor Genotype Specifically in Males
Xie P, Kranzler HR, Zhang H, Oslin D, Anton RF, Farrer LA, Gelernter J. Childhood Adversity Increases Risk for Nicotine Dependence and Interacts with α5 Nicotinic Acetylcholine Receptor Genotype Specifically in Males. Neuropsychopharmacology 2011, 37: 669-676. PMID: 22012472, PMCID: PMC3260970, DOI: 10.1038/npp.2011.240.Peer-Reviewed Original ResearchConceptsChildhood adversityRs16969968 genotypeND riskSex differencesNicotinic acetylcholine receptor genesAcetylcholine receptor genesPotential sex differencesNicotine dependence riskFagerstrom TestNicotine intakeSmoking riskIncrease riskNicotine dependenceRodent modelsReceptor genotypeND scoresEarly life experiencesEuropean AmericansReceptor geneWomenRiskGene × environment effectsMen