2022
Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond
Gaddis N, Mathur R, Marks J, Zhou L, Quach B, Waldrop A, Levran O, Agrawal A, Randesi M, Adelson M, Jeffries PW, Martin NG, Degenhardt L, Montgomery GW, Wetherill L, Lai D, Bucholz K, Foroud T, Porjesz B, Runarsdottir V, Tyrfingsson T, Einarsson G, Gudbjartsson DF, Webb BT, Crist RC, Kranzler HR, Sherva R, Zhou H, Hulse G, Wildenauer D, Kelty E, Attia J, Holliday EG, McEvoy M, Scott RJ, Schwab SG, Maher BS, Gruza R, Kreek MJ, Nelson EC, Thorgeirsson T, Stefansson K, Berrettini WH, Gelernter J, Edenberg HJ, Bierut L, Hancock DB, Johnson EO. Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond. Scientific Reports 2022, 12: 16873. PMID: 36207451, PMCID: PMC9546890, DOI: 10.1038/s41598-022-21003-y.Peer-Reviewed Original ResearchConceptsGenome-wide significant associationMulti-trait genome-wide association studyNovel genome-wide significant associationsGenome-wide association studiesGenomic structural equationGene-based analysisRelated traitsAssociation studiesGenetic correlationsEuropean ancestryA118G variantConsortium dataNew geneticsG variantGWASPPP6CLociPleiotropicGeneticsVariantsTraitsPhenotypeOA phenotypeFurinAncestrySex-Specific Genetic and Transcriptomic Liability to Neuroticism
Wendt FR, Pathak GA, Singh K, Stein MB, Koenen KC, Krystal JH, Gelernter J, Davis LK, Polimanti R. Sex-Specific Genetic and Transcriptomic Liability to Neuroticism. Biological Psychiatry 2022, 93: 243-252. PMID: 36244801, PMCID: PMC10508260, DOI: 10.1016/j.biopsych.2022.07.019.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesTranscriptomic profilesAssociation studiesSingle nucleotide polymorphism heritabilityGene expression variationGenome-wide significanceSex-specific geneticChromosomal variationTranscriptomic changesRisk lociExpression variationBiological processesMolecular pathwaysLociPolygenic associationSex-specific effectsGenetic correlatesPolygenic scoresUK BiobankGenetic riskNCOA6GeneticsHeritabilityPathwayFemales
2021
Integration of evidence across human and model organism studies: A meeting report
Palmer RHC, Johnson EC, Won H, Polimanti R, Kapoor M, Chitre A, Bogue MA, Benca‐Bachman C, Parker CC, Verma A, Reynolds T, Ernst J, Bray M, Bin Kwon S, Lai D, Quach BC, Gaddis NC, Saba L, Chen H, Hawrylycz M, Zhang S, Zhou Y, Mahaffey S, Fischer C, Sanchez‐Roige S, Bandrowski A, Lu Q, Shen L, Philip V, Gelernter J, Bierut LJ, Hancock DB, Edenberg HJ, Johnson EO, Nestler EJ, Barr PB, Prins P, Smith DJ, Akbarian S, Thorgeirsson T, Walton D, Baker E, Jacobson D, Palmer AA, Miles M, Chesler EJ, Emerson J, Agrawal A, Martone M, Williams RW. Integration of evidence across human and model organism studies: A meeting report. Genes Brain & Behavior 2021, 20: e12738. PMID: 33893716, PMCID: PMC8365690, DOI: 10.1111/gbb.12738.Peer-Reviewed Original ResearchModel organism studiesModel organismsOrganism studiesDeeper mechanistic insightsPhenotypic dataGenomic researchOmics dataHuman geneticsMechanistic insightsEpigeneticsComputational biologyDiverse groupGeneticsBiological sciencesOrganismsBiologySpeciesHumansFair Data SharingData integrationCurrent toolsNew opportunitiesFundamental gap
2020
Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits
Quach BC, Bray MJ, Gaddis NC, Liu M, Palviainen T, Minica CC, Zellers S, Sherva R, Aliev F, Nothnagel M, Young KA, Marks JA, Young H, Carnes MU, Guo Y, Waldrop A, Sey NYA, Landi MT, McNeil DW, Drichel D, Farrer LA, Markunas CA, Vink JM, Hottenga JJ, Iacono WG, Kranzler HR, Saccone NL, Neale MC, Madden P, Rietschel M, Marazita ML, McGue M, Won H, Winterer G, Grucza R, Dick DM, Gelernter J, Caporaso NE, Baker TB, Boomsma DI, Kaprio J, Hokanson JE, Vrieze S, Bierut LJ, Johnson EO, Hancock DB. Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits. Nature Communications 2020, 11: 5562. PMID: 33144568, PMCID: PMC7642344, DOI: 10.1038/s41467-020-19265-z.Peer-Reviewed Original ResearchConceptsGenome-wide significant lociGenome-wide association studiesNearby gene expressionExpression of genesSmoking traitsGenetic architectureSignificant lociGenetic variationMultiple traitsGene expressionAssociation studiesLociTraitsGenetic knowledgeComposite phenotypeUK BiobankExpressionTENM2GNAI1GenesGeneticsVariantsPhenotype
2019
Multivariate Analyses Reveal Biological Components Related to Neuronal Signaling and Immunity Mediating Electroencephalograms Abnormalities in Alcohol‐Dependent Individuals from the Collaborative Study on the Genetics of Alcoholism Cohort
Meda SA, Narayanan B, Chorlian D, Meyers JL, Gelernter J, Hesselbrock V, Bauer L, Calhoun VD, Porjesz B, Pearlson G. Multivariate Analyses Reveal Biological Components Related to Neuronal Signaling and Immunity Mediating Electroencephalograms Abnormalities in Alcohol‐Dependent Individuals from the Collaborative Study on the Genetics of Alcoholism Cohort. Alcohol Clinical And Experimental Research 2019, 43: 1462-1477. PMID: 31009096, DOI: 10.1111/acer.14063.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAlcoholismCase-Control StudiesCohort StudiesElectroencephalographyFemaleGenetic Association StudiesGenome-Wide Association StudyGenotypeHumansMaleMiddle AgedMultigene FamilyNeuronsPhenotypePolymorphism, Single NucleotideSignal TransductionSubstance-Related DisordersWhite PeopleYoung AdultConceptsGenetic clustersSingle nucleotide polymorphism dataSignificant genotype-phenotype associationsNucleotide polymorphism dataLipid/cholesterol metabolismLinkage-based analysisGenotype-phenotype relationshipsGenotype-phenotype associationsGene clusterCell signalingPolymorphism dataMolecular mechanismsAlcoholism datasetGenomewide associationTop hitsGenetic componentNeuronal signalingGeneticsSignalingBiological componentsRelationship pairsCholesterol metabolismNeurogenesisSNP componentParallel independent component analysis
2018
Local adaptation in European populations affected the genetics of psychiatric disorders and behavioral traits
Polimanti R, Kayser MH, Gelernter J. Local adaptation in European populations affected the genetics of psychiatric disorders and behavioral traits. Genome Medicine 2018, 10: 24. PMID: 29580271, PMCID: PMC5870256, DOI: 10.1186/s13073-018-0532-7.Peer-Reviewed Original ResearchConceptsLocal adaptationPathogen diversityEuropean populationsBehavioral traitsGenome-wide investigationGenome-wide dataPolygenic risk score analysisProtozoan diversityWinter minimum temperaturesGenetic diversityEvolutionary mechanismsPositive selectionWidespread signalMolecular mechanismsTop findingsRisk score analysisDiversityTraitsCommon variationBehavioral phenotypesAdaptationGeneticsPopulationPhenotypeMechanism
2016
Meta-Analyses of Genome-Wide Association Data Hold New Promise for Addiction Genetics.
Agrawal A, Edenberg HJ, Gelernter J. Meta-Analyses of Genome-Wide Association Data Hold New Promise for Addiction Genetics. Journal Of Studies On Alcohol And Drugs 2016, 77: 676-80. PMID: 27588522, PMCID: PMC5015465, DOI: 10.15288/jsad.2016.77.676.Peer-Reviewed Original ResearchEvidence of Polygenic Adaptation in the Systems Genetics of Anthropometric Traits
Polimanti R, Yang BZ, Zhao H, Gelernter J. Evidence of Polygenic Adaptation in the Systems Genetics of Anthropometric Traits. PLOS ONE 2016, 11: e0160654. PMID: 27537407, PMCID: PMC4990182, DOI: 10.1371/journal.pone.0160654.Peer-Reviewed Original ResearchConceptsPolygenic adaptationNatural selectionSystems geneticsProtein interaction networksWide association studyPolygenic mechanismsEuropean populationsPolygenic selectionAnthropometric traitsGene networksHuman genomeEpistatic interactionsInteraction networksEnrichment analysisGenetic signaturesSystems biologyAssociation studiesLipid transportMolecular processesAdaptation signalsLocomotory behaviorTraitsSelective mechanismGeneticsInfection resistance
2015
Evidence of CNIH3 involvement in opioid dependence
Nelson EC, Agrawal A, Heath AC, Bogdan R, Sherva R, Zhang B, Al-Hasani R, Bruchas MR, Chou YL, Demers CH, Carey CE, Conley ED, Fakira AK, Farrer LA, Goate A, Gordon S, Henders AK, Hesselbrock V, Kapoor M, Lynskey MT, Madden PA, Moron JA, Rice JP, Saccone NL, Schwab SG, Shand FL, Todorov AA, Wallace L, Wang T, Wray NR, Zhou X, Degenhardt L, Martin NG, Hariri AR, Kranzler HR, Gelernter J, Bierut LJ, Clark DJ, Montgomery GW. Evidence of CNIH3 involvement in opioid dependence. Molecular Psychiatry 2015, 21: 608-614. PMID: 26239289, PMCID: PMC4740268, DOI: 10.1038/mp.2015.102.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsGenome-wide association studiesComputational genetic analysisEpigenetic annotationsGenetic analysisAssociation studiesGenetic studiesStudy of AddictionVivo functionalityMouse strainsOpioid dependenceNeurogenetics StudySevere addictive disordersΑ-aminoGenesOpioid misusersGeneticsCnih3SNPsDuke Neurogenetics StudyHaplotypesPhenotypeA alleleAllelesFetal brain
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 variationVariantsSequencingSLC6A4 polymorphism, population genetics, and psychiatric traits
Gelernter J. SLC6A4 polymorphism, population genetics, and psychiatric traits. Human Genetics 2014, 133: 459-461. PMID: 24385047, PMCID: PMC3992709, DOI: 10.1007/s00439-013-1412-2.Peer-Reviewed Original Research
2013
Integrating GWASs and Human Protein Interaction Networks Identifies a Gene Subnetwork Underlying Alcohol Dependence
Han S, Yang BZ, Kranzler HR, Liu X, Zhao H, Farrer LA, Boerwinkle E, Potash JB, Gelernter J. Integrating GWASs and Human Protein Interaction Networks Identifies a Gene Subnetwork Underlying Alcohol Dependence. American Journal Of Human Genetics 2013, 93: 1027-1034. PMID: 24268660, PMCID: PMC3853414, DOI: 10.1016/j.ajhg.2013.10.021.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesHuman protein interaction networkGene subnetworksProtein interaction networksIntegrating Genome-Wide Association StudyInteraction networksHuman complex disordersSubnetworks of genesGWAS data setsFunctional enrichment analysisAD risk genesEnrichment analysisProtein productsAssociation studiesSignificant genetic contributionGenesGenetics of AlcoholismStudy of AddictionGenetic contributionGeneticsComplex disorderAD etiologyCation transportImportant cluesEuropean descentGenome-Wide Association Study of Opioid Dependence: Multiple Associations Mapped to Calcium and Potassium Pathways
Gelernter J, Kranzler HR, Sherva R, Koesterer R, Almasy L, Zhao H, Farrer LA. Genome-Wide Association Study of Opioid Dependence: Multiple Associations Mapped to Calcium and Potassium Pathways. Biological Psychiatry 2013, 76: 66-74. PMID: 24143882, PMCID: PMC3992201, DOI: 10.1016/j.biopsych.2013.08.034.Peer-Reviewed Original ResearchMeSH KeywordsAllelesBlack or African AmericanCalcium ChannelsCalcium SignalingDatabases, GeneticGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansLong-Term PotentiationOpioid-Related DisordersPolymorphism, Single NucleotidePotassiumPotassium Channels, Voltage-GatedSignal TransductionWhite PeopleConceptsGenome-wide association studiesSingle nucleotide polymorphismsAssociation studiesSignificant single nucleotide polymorphismsGenomes reference panelGWAS dataMultiple lociPathway analysisCalcium signalingRisk variantsGenesNucleotide polymorphismsPotassium pathwaysSimilar pathwaysReference panelAdditional genotypesPathwayMost significant resultsMultiple associationsLong-term potentiationLociGeneticsSignalingRisk pathwaysMicroarrayAssociation of Gamma-Aminobutyric Acid A Receptor α2 Gene (GABRA2) with Alcohol Use Disorder
Li D, Sulovari A, Cheng C, Zhao H, Kranzler HR, Gelernter J. Association of Gamma-Aminobutyric Acid A Receptor α2 Gene (GABRA2) with Alcohol Use Disorder. Neuropsychopharmacology 2013, 39: 907-918. PMID: 24136292, PMCID: PMC3924525, DOI: 10.1038/npp.2013.291.Peer-Reviewed Original ResearchConceptsReceptor geneGABA receptor genesGABAA receptor genesCandidate gene association studiesSAGE data setsBonferroni-corrected thresholdGene association studiesSingle nucleotide polymorphismsAssociation studiesGenotype dataStudy of AddictionGamma-aminobutyric acidMammalian brainGenesComplex disorderGABRA2 single nucleotide polymorphismsSubstance dependenceMajor inhibitory neurotransmitterGeneticsInhibitory neurotransmitterVariantsGABA receptorsSignificant associationSubstance abuseMethamphetamine dependence
2012
Linkage Analysis Followed by Association Show NRG1 Associated with Cannabis Dependence in African Americans
Han S, Yang BZ, Kranzler HR, Oslin D, Anton R, Farrer LA, Gelernter J. Linkage Analysis Followed by Association Show NRG1 Associated with Cannabis Dependence in African Americans. Biological Psychiatry 2012, 72: 637-644. PMID: 22520967, PMCID: PMC3699339, DOI: 10.1016/j.biopsych.2012.02.038.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsSusceptibility genesLinkage peakGenome-wide linkage scanAssociation analysisGenome-wide association studiesStudy of AddictionStrong linkage evidenceChromosome 8p21.1AA sampleLinkage scanLocal ancestryAssociation studiesGenetic studiesLinkage analysisReplicated associationsLinkage evidenceGenetic variantsGenesNucleotide polymorphismsGenetic contributionGeneticsNRG1Environment samplesReplication study
2010
Genetics of drug dependence
Gelernter J, Kranzler HR. Genetics of drug dependence. Dialogues In Clinical Neuroscience 2010, 12: 77-84. PMID: 20373669, PMCID: PMC3181942, DOI: 10.31887/dcns.2010.12.1/jgelernter.Peer-Reviewed Original ResearchChapter 11 Genetic Basis of Social Anxiety Disorder
Stein M, Gelernter J. Chapter 11 Genetic Basis of Social Anxiety Disorder. 2010, 313-322. DOI: 10.1016/b978-0-12-375096-9.00011-0.Peer-Reviewed Original Research
2009
Genetics of alcohol dependence
Gelernter J, Kranzler HR. Genetics of alcohol dependence. Human Genetics 2009, 126: 91-99. PMID: 19533172, PMCID: PMC3773848, DOI: 10.1007/s00439-009-0701-2.Peer-Reviewed Original Research
2008
Substance dependence low-density whole genome association study in two distinct American populations
Yu Y, Kranzler HR, Panhuysen C, Weiss RD, Poling J, Farrer LA, Gelernter J. Substance dependence low-density whole genome association study in two distinct American populations. Human Genetics 2008, 123: 495. PMID: 18438686, PMCID: PMC3428017, DOI: 10.1007/s00439-008-0501-0.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphism (SNP) markersWhole-genome association studiesFuture candidate gene studiesGenome association studiesCandidate gene studiesPotential biological relevancePolymorphism markersGenetic basisAssociation studiesGenetic markersHigh heritabilityGene studiesCocaine-induced paranoiaBiological relevanceGenesComplex disorderNew hypothesisFamilyAmerican populationGeneticsHeritabilityMarkers
2000
Variant detection at the δ opioid receptor (OPRD1) locus and population genetics of a novel variant affecting protein sequence
Gelernter J, Kranzler H. Variant detection at the δ opioid receptor (OPRD1) locus and population genetics of a novel variant affecting protein sequence. Human Genetics 2000, 107: 86-88. PMID: 10982041, DOI: 10.1007/s004390000340.Peer-Reviewed Original ResearchConceptsPopulation geneticsProtein sequencesPopulation genetic dataAmino acid sequenceNovel variantsΔ locusAcid sequenceGenetic dataReceptor locusExon 1LociReceptor geneOpioid receptor geneCommon variantsEuropean populationsAllele frequenciesGeneticsVariant detectionSequenceAllelesOpioid dependenceVariantsPhysiologic effectsG alleleSubstance dependence