2024
Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program
Verma A, Huffman J, Rodriguez A, Conery M, Liu M, Ho Y, Kim Y, Heise D, Guare L, Panickan V, Garcon H, Linares F, Costa L, Goethert I, Tipton R, Honerlaw J, Davies L, Whitbourne S, Cohen J, Posner D, Sangar R, Murray M, Wang X, Dochtermann D, Devineni P, Shi Y, Nandi T, Assimes T, Brunette C, Carroll R, Clifford R, Duvall S, Gelernter J, Hung A, Iyengar S, Joseph J, Kember R, Kranzler H, Kripke C, Levey D, Luoh S, Merritt V, Overstreet C, Deak J, Grant S, Polimanti R, Roussos P, Shakt G, Sun Y, Tsao N, Venkatesh S, Voloudakis G, Justice A, Begoli E, Ramoni R, Tourassi G, Pyarajan S, Tsao P, O'Donnell C, Muralidhar S, Moser J, Casas J, Bick A, Zhou W, Cai T, Voight B, Cho K, Gaziano J, Madduri R, Damrauer S, Liao K. Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. Science 2024, 385: eadj1182. PMID: 39024449, DOI: 10.1126/science.adj1182.Peer-Reviewed Original ResearchConceptsMillion Veteran ProgramNon-European populationsVeteran ProgramGenetic architectureAtlas of genetic associationsVeterans Affairs Million Veteran ProgramVA Million Veteran ProgramGenomic risk lociGenome-wide associationHuman genetic studiesHealth disparitiesUnited States veteransCausal variantsRisk lociGenetic insightsGenetic studiesGenetic associationGenetic causeStates veteransDiverse populationsDisease factorsLack of inclusionLongitudinal studyParticipantsTraits
2020
Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium
Polimanti R, Walters RK, Johnson EC, McClintick JN, Adkins AE, Adkins DE, Bacanu SA, Bierut LJ, Bigdeli TB, Brown S, Bucholz KK, Copeland WE, Costello EJ, Degenhardt L, Farrer LA, Foroud TM, Fox L, Goate AM, Grucza R, Hack LM, Hancock DB, Hartz SM, Heath AC, Hewitt JK, Hopfer CJ, Johnson EO, Kendler KS, Kranzler HR, Krauter K, Lai D, Madden PAF, Martin NG, Maes HH, Nelson EC, Peterson RE, Porjesz B, Riley BP, Saccone N, Stallings M, Wall TL, Webb BT, Wetherill L, Edenberg H, Agrawal A, Gelernter J. Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium. Molecular Psychiatry 2020, 25: 1673-1687. PMID: 32099098, PMCID: PMC7392789, DOI: 10.1038/s41380-020-0677-9.Peer-Reviewed Original ResearchA 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
2017
Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior
Tielbeek JJ, Johansson A, Polderman TJC, Rautiainen MR, Jansen P, Taylor M, Tong X, Lu Q, Burt AS, Tiemeier H, Viding E, Plomin R, Martin NG, Heath AC, Madden PAF, Montgomery G, Beaver KM, Waldman I, Gelernter J, Kranzler HR, Farrer LA, Perry JRB, Munafò M, LoParo D, Paunio T, Tiihonen J, Mous SE, Pappa I, de Leeuw C, Watanabe K, Hammerschlag AR, Salvatore JE, Aliev F, Bigdeli TB, Dick D, Faraone SV, Popma A, Medland SE, Posthuma D. Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior. JAMA Psychiatry 2017, 74: 1242-1250. PMID: 28979981, PMCID: PMC6309228, DOI: 10.1001/jamapsychiatry.2017.3069.Peer-Reviewed Original ResearchConceptsNovel genetic risk variantsSingle nucleotide polymorphism-based heritabilityGenome-wide association studiesGenome-wide association dataCausal genetic variantsGenome-wide genotypesPolygenic risk score analysisGenetic architectureGenetic risk variantsInverse genetic correlationPromising lociAssociation studiesBiological pathwaysPleiotropic associationsQuantitative phenotypesGenetic correlationsPsychiatric traitsAssociation dataGenetic effectsRisk variantsRisk score analysisGenetic variantsGenetic originDiscovery sampleTraitsGenetic Risk Variants Associated With Comorbid Alcohol Dependence and Major Depression
Zhou H, Polimanti R, Yang BZ, Wang Q, Han S, Sherva R, Nuñez YZ, Zhao H, Farrer LA, Kranzler HR, Gelernter J. Genetic Risk Variants Associated With Comorbid Alcohol Dependence and Major Depression. JAMA Psychiatry 2017, 74: 1234-1241. PMID: 29071344, PMCID: PMC6331050, DOI: 10.1001/jamapsychiatry.2017.3275.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismBlack or African AmericanComorbidityDepressive Disorder, MajorDiagnostic and Statistical Manual of Mental DisordersFemaleGenetic Predisposition to DiseaseGenetic VariationHumansMaleMiddle AgedMultifactorial InheritanceOrgan SizePutamenSemaphorin-3AUnited StatesWhite PeopleConceptsGenome-wide association studiesGenetic risk variantsNeuropsychiatric traitsAssociation studiesRisk variantsPolygenic risk allelesPolygenic risk scoresGenetic mechanismsGenetic basisAmerican data setMolecular natureTraitsCriterion countsGenetic causePossible genetic causesMD comorbidityRisk allelesComorbid alcohol dependenceGenetically determined schizophrenia is not associated with impaired glucose homeostasis
Polimanti R, Gelernter J, Stein DJ. Genetically determined schizophrenia is not associated with impaired glucose homeostasis. Schizophrenia Research 2017, 195: 286-289. PMID: 29092750, PMCID: PMC5924728, DOI: 10.1016/j.schres.2017.10.033.Peer-Reviewed Original ResearchGenetic risk variants for social anxiety
Stein MB, Chen C, Jain S, Jensen KP, He F, Heeringa SG, Kessler RC, Maihofer A, Nock MK, Ripke S, Sun X, Thomas ML, Ursano RJ, Smoller JW, Gelernter J, Collaborators O. Genetic risk variants for social anxiety. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2017, 174: 120-131. PMID: 28224735, PMCID: PMC5325045, DOI: 10.1002/ajmg.b.32520.Peer-Reviewed Original Research
2016
Genome-wide Association Study of Cannabis Dependence Severity, Novel Risk Variants, and Shared Genetic Risks
Sherva R, Wang Q, Kranzler H, Zhao H, Koesterer R, Herman A, Farrer LA, Gelernter J. Genome-wide Association Study of Cannabis Dependence Severity, Novel Risk Variants, and Shared Genetic Risks. JAMA Psychiatry 2016, 73: 472. PMID: 27028160, PMCID: PMC4974817, DOI: 10.1001/jamapsychiatry.2016.0036.Peer-Reviewed Original ResearchConceptsCannabis dependenceNeuronal calcium homeostasisGenetic factorsMajor depressive disorderSushi multiple domains-1 (CSMD1) geneSubstance abuse treatment centersSpecific genetic risk factorsGenetic risk factorsShared genetic riskPotential genetic factorsCentral nervous system developmentCriterion countsCannabis dependence severityDomain 1 geneCAD riskMean ageRisk factorsDepressive disorderNervous system developmentMajor depressionLarge cohortMAIN OUTCOMEGenome-wide association studiesTreatment centersCalcium homeostasisCHRNA5/A3/B4 Variant rs3743078 and Nicotine-Related Phenotypes: Indirect Effects Through Nicotine Craving.
Shmulewitz D, Meyers JL, Wall MM, Aharonovich E, Frisch A, Spivak B, Weizman A, Edenberg HJ, Gelernter J, Hasin DS. CHRNA5/A3/B4 Variant rs3743078 and Nicotine-Related Phenotypes: Indirect Effects Through Nicotine Craving. Journal Of Studies On Alcohol And Drugs 2016, 77: 227-37. PMID: 26997181, PMCID: PMC4803655, DOI: 10.15288/jsad.2016.77.227.Peer-Reviewed Original ResearchConceptsNicotine cravingFTND scoreNeuronal nicotinic acetylcholine receptor geneNicotine use disorderNicotinic acetylcholine receptor genesAcetylcholine receptor genesLifetime smokersCigarette smokingMore cigarettesHigher scoresNicotine dependenceFagerström TestTherapeutic targetUse disordersG alleleAllele GCHRNA5-CHRNA3CravingReceptor geneScoresSizeable proportionFTNDCigarettesHousehold sampleSignificant indirect effect
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
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 effectGenetics 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
2012
Variation in regulator of G-protein signaling 17 gene (RGS17) is associated with multiple substance dependence diagnoses
Zhang H, Wang F, Kranzler HR, Anton RF, Gelernter J. Variation in regulator of G-protein signaling 17 gene (RGS17) is associated with multiple substance dependence diagnoses. Behavioral And Brain Functions 2012, 8: 23. PMID: 22591552, PMCID: PMC3406967, DOI: 10.1186/1744-9081-8-23.Peer-Reviewed Original ResearchAdultAlcoholismBlack or African AmericanCocaine-Related DisordersFemaleGenetic VariationHaplotypesHumansLinkage DisequilibriumMaleMarijuana AbuseMiddle AgedOpioid-Related DisordersPolymorphism, Single NucleotideRGS ProteinsRisk FactorsSignal TransductionSubstance-Related DisordersUnited StatesWhite People
2011
GABRG1 and GABRA2 Variation Associated with Alcohol Dependence in African Americans
Ittiwut C, Yang B, Kranzler HR, Anton RF, Hirunsatit R, Weiss RD, Covault J, Farrer LA, Gelernter J. GABRG1 and GABRA2 Variation Associated with Alcohol Dependence in African Americans. Alcohol Clinical And Experimental Research 2011, 36: 588-593. PMID: 21919924, PMCID: PMC3250564, DOI: 10.1111/j.1530-0277.2011.01637.x.Peer-Reviewed Original ResearchRare Nonsynonymous Variants in Alpha-4 Nicotinic Acetylcholine Receptor Gene Protect Against Nicotine Dependence
Xie P, Kranzler HR, Krauthammer M, Cosgrove KP, Oslin D, Anton RF, Farrer LA, Picciotto MR, Krystal JH, Zhao H, Gelernter J. Rare Nonsynonymous Variants in Alpha-4 Nicotinic Acetylcholine Receptor Gene Protect Against Nicotine Dependence. Biological Psychiatry 2011, 70: 528-536. PMID: 21683344, PMCID: PMC3199609, DOI: 10.1016/j.biopsych.2011.04.017.Peer-Reviewed Original ResearchVariation in Genes Encoding the Neuroactive Steroid Synthetic Enzymes 5α‐Reductase Type 1 and 3α‐Reductase Type 2 Is Associated With Alcohol Dependence
Milivojevic V, Kranzler HR, Gelernter J, Burian L, Covault J. Variation in Genes Encoding the Neuroactive Steroid Synthetic Enzymes 5α‐Reductase Type 1 and 3α‐Reductase Type 2 Is Associated With Alcohol Dependence. Alcohol Clinical And Experimental Research 2011, 35: 946-952. PMID: 21323680, PMCID: PMC3083475, DOI: 10.1111/j.1530-0277.2010.01425.x.Peer-Reviewed Original ResearchMeSH Keywords3-Hydroxysteroid Dehydrogenases3-Oxo-5-alpha-Steroid 4-DehydrogenaseAdultAlcoholismAldo-Keto Reductase Family 1 Member C3Base SequenceCase-Control StudiesFemaleGenetic VariationHumansHydroxyprostaglandin DehydrogenasesMaleMembrane ProteinsMiddle AgedMolecular Sequence DataPolymorphism, Single NucleotideYoung AdultConceptsEndogenous neuroactive steroidsNeuroactive steroidsAlcohol dependenceAlcohol effectsType 2Minor alleleNon-Hispanic CaucasiansRatio of dihydrotestosteroneBladder cancerG alleleC alleleSteroid biosynthetic enzymesType 1Important mediatorKey mediatorSteroidsSingle nucleotide polymorphismsCase-control sampleHuman brainType IMarkersBiological phenotypesNucleotide polymorphismsIndirect evidenceMediatorsVariation in NGFB is associated with primary affective disorders in women
Cui D, Zhang H, Yang B, Listman JB, Li D, Price LH, Carpenter LL, Tyrka AR, Anton RF, Kranzler HR, Gelernter J. Variation in NGFB is associated with primary affective disorders in women. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2011, 156: 401-412. PMID: 21294249, PMCID: PMC3108453, DOI: 10.1002/ajmg.b.31175.Peer-Reviewed Original Research
2010
A Common Genetic Variant in the Neurexin Superfamily Member CNTNAP2 Is Associated with Increased Risk for Selective Mutism and Social Anxiety-Related Traits
Stein MB, Yang BZ, Chavira DA, Hitchcock CA, Sung SC, Shipon-Blum E, Gelernter J. A Common Genetic Variant in the Neurexin Superfamily Member CNTNAP2 Is Associated with Increased Risk for Selective Mutism and Social Anxiety-Related Traits. Biological Psychiatry 2010, 69: 825-831. PMID: 21193173, PMCID: PMC3079072, DOI: 10.1016/j.biopsych.2010.11.008.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAllelesChildChild, PreschoolFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGenetic VariationGenotypeHaplotypesHumansLinear ModelsMaleMembrane ProteinsMutismNerve Tissue ProteinsOdds RatioPhobic DisordersPolymorphism, Single NucleotidePsychiatric Status Rating ScalesSelf ReportSurveys and QuestionnairesVariation in the gene encoding the serotonin transporter is associated with a measure of sociopathy in alcoholics
Herman AI, Conner TS, Anton RF, Gelernter J, Kranzler HR, Covault J. Variation in the gene encoding the serotonin transporter is associated with a measure of sociopathy in alcoholics. Addiction Biology 2010, 16: 124-132. PMID: 20192950, PMCID: PMC2888710, DOI: 10.1111/j.1369-1600.2009.00197.x.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholics AnonymousAlcoholismAllelesAntisocial Personality DisorderCognitive Behavioral TherapyFemaleGene FrequencyGenetic VariationGenotypeHumansMaleMiddle AgedMotivationPersonality InventoryPolymorphism, GeneticPsychotherapySerotonin Plasma Membrane Transport ProteinsSex FactorsConceptsAlcohol dependenceAlcohol use disorderAlcohol Treatment TrialSerotonin transporter proteinSocialization scoresTreatment trialsPsychiatric disordersUse disordersInsertion-deletion polymorphismTri-allelicInventory scoresSerotonin transporterSingle nucleotide polymorphismsWomenLower socialization scoresProject MATCHRegression analysisScoresShort alleleGenetic Associations of Brain Structural Networks in Schizophrenia: A Preliminary Study
Jagannathan K, Calhoun VD, Gelernter J, Stevens MC, Liu J, Bolognani F, Windemuth A, Ruaño G, Assaf M, Pearlson GD. Genetic Associations of Brain Structural Networks in Schizophrenia: A Preliminary Study. Biological Psychiatry 2010, 68: 657-666. PMID: 20691427, PMCID: PMC2990476, DOI: 10.1016/j.biopsych.2010.06.002.Peer-Reviewed Original ResearchConceptsSpecific structural brain abnormalitiesMagnetic resonance imaging (MRI) scansSmall sample sizeHealthy control subjectsStructural brain abnormalitiesStructural magnetic resonance imaging (MRI) scansGray matter deficitsResonance imaging scansCortical gray matterNormal central nervous system developmentRisk genesCentral nervous system developmentBrain structural networksControl subjectsImaging scansBrain abnormalitiesNervous system developmentIllness markersSchizophrenia pathophysiologySchizophrenia risk genesGenetic componentTemporal lobeBrain areasEuropean-American subjectsSchizophrenia patients