Featured Publications
Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program
Stein MB, Levey DF, Cheng Z, Wendt FR, Harrington K, Pathak GA, Cho K, Quaden R, Radhakrishnan K, Girgenti MJ, Ho YA, Posner D, Aslan M, Duman RS, Zhao H, Polimanti R, Concato J, Gelernter J. Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program. Nature Genetics 2021, 53: 174-184. PMID: 33510476, PMCID: PMC7972521, DOI: 10.1038/s41588-020-00767-x.Peer-Reviewed Original ResearchConceptsGenome-wide association analysisAssociation analysisMillion Veteran ProgramGenomic structural equation modelingSignificant lociGenetic varianceGene expressionDrug repositioning candidatesBiological coherenceVeteran ProgramMultiple testing correctionSymptom phenotypeLociRepositioning candidatesAfrican ancestryHeritabilityPhenotypeAncestryExpressionPTSD symptom factorsRegionSubdomainsEnrichment
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
Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes
Chen J, Loukola A, Gillespie NA, Peterson R, Jia P, Riley B, Maes H, Dick DM, Kendler KS, Damaj MI, Miles MF, Zhao Z, Li MD, Vink JM, Minica CC, Willemsen G, Boomsma DI, Qaiser B, Madden PAF, Korhonen T, Jousilahti P, Hällfors J, Gelernter J, Kranzler HR, Sherva R, Farrer L, Maher B, Vanyukov M, Taylor M, Ware JJ, Munafò MR, Lutz SM, Hokanson JE, Gu F, Landi MT, Caporaso NE, Hancock DB, Gaddis NC, Baker TB, Bierut LJ, Johnson EO, Chenoweth M, Lerman C, Tyndale R, Kaprio J, Chen X. Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes. Nicotine & Tobacco Research 2019, 22: 900-909. PMID: 31294817, PMCID: PMC7249921, DOI: 10.1093/ntr/ntz099.Peer-Reviewed Original ResearchConceptsGenome-Wide Meta-AnalysisGene-based analysisChemokine signaling pathwaysGenetic architectureActin cytoskeletonNew lociReceptor recyclingMAPK signalingPathway interactionsBiological pathwaysSignaling pathwaysAxon guidanceNovel pathwayPhenotypeNovel candidatesEuropean ancestryPathwayReplication sampleNetwork analysisReplicationIno80CCytoskeletonCOPB2EndocytosisSORBS2Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium
Polimanti R, Peterson RE, Ong JS, MacGregor S, Edwards AC, Clarke TK, Frank J, Gerring Z, Gillespie NA, Lind PA, Maes HH, Martin NG, Mbarek H, Medland SE, Streit F, Agrawal A, Edenberg H, Kendler K, Lewis C, Sullivan P, Wray N, Gelernter J, Derks E. Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium. Psychological Medicine 2019, 49: 1218-1226. PMID: 30929657, PMCID: PMC6565601, DOI: 10.1017/s0033291719000667.Peer-Reviewed Original ResearchConceptsMajor depressionAlcohol dependenceAlcohol consumptionPsychiatric Genomics ConsortiumImportant public health concernMendelian randomizationPublic health concernUK BiobankClinical associationsHealth concernMR analysisReverse causationCausal roleNon-significant resultsCausal relationshipGenetic liabilityGenomics ConsortiumLinkage disequilibrium score regressionIntervention efforts
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 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
Eye color: A potential indicator of alcohol dependence risk in European Americans
Sulovari A, Kranzler HR, Farrer LA, Gelernter J, Li D. Eye color: A potential indicator of alcohol dependence risk in European Americans. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2015, 168: 347-353. PMID: 25921801, DOI: 10.1002/ajmg.b.32316.Peer-Reviewed Original ResearchMeSH KeywordsAlcoholismEye ColorFemaleGenotypeHumansLinkage DisequilibriumMalePolymorphism, Single NucleotideRiskWhite PeopleConceptsAlcohol dependenceLight-eyed individualsDark-eyed individualsPopulation-based studyLight eye colorBlue eye colorEvidence of associationEye colorRisk factorsEtiological factorsHigh prevalenceEye color geneLogistic regressionAD-associated genesMore alcoholArchival samplesColor genesAssociationEuropean ancestry subjectsReceptor gene clusterIndividualsStratificationBrown eye colorFurther characterizationAssociation studies
2013
Distinct Loci in the CHRNA5/CHRNA3/CHRNB4 Gene Cluster Are Associated With Onset of Regular Smoking
Stephens SH, Hartz SM, Hoft NR, Saccone NL, Corley RC, Hewitt JK, Hopfer CJ, Breslau N, Coon H, Chen X, Ducci F, Dueker N, Franceschini N, Frank J, Han Y, Hansel NN, Jiang C, Korhonen T, Lind PA, Liu J, Lyytikäinen L, Michel M, Shaffer JR, Short SE, Sun J, Teumer A, Thompson JR, Vogelzangs N, Vink JM, Wenzlaff A, Wheeler W, Yang B, Aggen SH, Balmforth AJ, Baumeister SE, Beaty TH, Benjamin DJ, Bergen AW, Broms U, Cesarini D, Chatterjee N, Chen J, Cheng Y, Cichon S, Couper D, Cucca F, Dick D, Foroud T, Furberg H, Giegling I, Gillespie NA, Gu F, Hall AS, Hällfors J, Han S, Hartmann AM, Heikkilä K, Hickie IB, Hottenga JJ, Jousilahti P, Kaakinen M, Kähönen M, Koellinger PD, Kittner S, Konte B, Landi M, Laatikainen T, Leppert M, Levy SM, Mathias RA, McNeil DW, Medland SE, Montgomery GW, Murray T, Nauck M, North KE, Paré PD, Pergadia M, Ruczinski I, Salomaa V, Viikari J, Willemsen G, Barnes KC, Boerwinkle E, Boomsma DI, Caporaso N, Edenberg HJ, Francks C, Gelernter J, Grabe HJ, Hops H, Jarvelin M, Johannesson M, Kendler KS, Lehtimäki T, Magnusson PK, Marazita ML, Marchini J, Mitchell BD, Nöthen MM, Penninx BW, Raitakari O, Rietschel M, Rujescu D, Samani NJ, Schwartz AG, Shete S, Spitz M, Swan GE, Völzke H, Veijola J, Wei Q, Amos C, Cannon DS, Grucza R, Hatsukami D, Heath A, Johnson EO, Kaprio J, Madden P, Martin NG, Stevens VL, Weiss RB, Kraft P, Bierut LJ, Ehringer MA. Distinct Loci in the CHRNA5/CHRNA3/CHRNB4 Gene Cluster Are Associated With Onset of Regular Smoking. Genetic Epidemiology 2013, 37: 846-859. PMID: 24186853, PMCID: PMC3947535, DOI: 10.1002/gepi.21760.Peer-Reviewed Original ResearchConceptsGene clusterAssociation signalsEarly smoking behaviourSmoking behaviorCHRNA5/A3/B4 gene clusterNicotinic acetylcholine receptor genesRobust association signalsNeuronal nicotinic acetylcholine receptor geneAcetylcholine receptor genesNicotine dependenceCHRNB4 gene clusterSignificant associationB4 gene clusterDistinct lociLung cancer riskRegular tobacco useAssociation resultsNicotine dependence phenotypesDependence phenotypesReceptor geneCotinine levelsRs1948PhenotypeRegular smokingProtective effectAssociation 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
Identification of POMC Exonic Variants Associated with Substance Dependence and Body Mass Index
Wang F, Gelernter J, Kranzler HR, Zhang H. Identification of POMC Exonic Variants Associated with Substance Dependence and Body Mass Index. PLOS ONE 2012, 7: e45300. PMID: 23028917, PMCID: PMC3444488, DOI: 10.1371/journal.pone.0045300.Peer-Reviewed Original ResearchConceptsBody mass indexSubstance dependenceMass indexExact testRare variantsAfrican AmericansNormal weight groupCommon variantsFisher's exact testProopiomelanocortin geneObese groupObese subjectsExonic variantsMelanocortin peptidesEuropean AmericansLogistic regressionCommon polymorphismsOverweightRare exonic variantsVariants AssociatedPopulation-specific mannerRiskAssociationObesityGroupVariation 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 ResearchAssociation of CHRNA4 polymorphisms with smoking behavior in two populations
Han S, Yang B, Kranzler HR, Oslin D, Anton R, Gelernter J. Association of CHRNA4 polymorphisms with smoking behavior in two populations. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2011, 156: 421-429. PMID: 21445957, PMCID: PMC3742073, DOI: 10.1002/ajmg.b.31177.Peer-Reviewed Original Research
2010
Variation in Nicotinic Acetylcholine Receptor Genes is Associated with Multiple Substance Dependence Phenotypes
Sherva R, Kranzler HR, Yu Y, Logue MW, Poling J, Arias AJ, Anton RF, Oslin D, Farrer LA, Gelernter J. Variation in Nicotinic Acetylcholine Receptor Genes is Associated with Multiple Substance Dependence Phenotypes. Neuropsychopharmacology 2010, 35: 1921-1931. PMID: 20485328, PMCID: PMC3055642, DOI: 10.1038/npp.2010.64.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlack or African AmericanChromosomes, Human, Pair 15Family HealthFemaleGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansLinkage DisequilibriumMaleMiddle AgedPhenotypePolymorphism, Single NucleotideReceptors, NicotinicSubstance-Related DisordersWhite PeopleConceptsGene clusterAssociation studiesNicotinic receptor gene clusterNicotinic acetylcholine receptor genesAcetylcholine receptor genesReceptor gene clusterStrongest association signalSubstance dependence phenotypesAssociation signalsImportance of variationChromosome 15q25.1Opposite risk allelePermutation-based correctionDependence phenotypesReplication setReceptor geneMultiple polymorphismsSNPsInteraction of FKBP5 with Childhood Adversity on Risk for Post-Traumatic Stress Disorder
Xie P, Kranzler HR, Poling J, Stein MB, Anton RF, Farrer LA, Gelernter J. Interaction of FKBP5 with Childhood Adversity on Risk for Post-Traumatic Stress Disorder. Neuropsychopharmacology 2010, 35: 1684-1692. PMID: 20393453, PMCID: PMC2946626, DOI: 10.1038/npp.2010.37.Peer-Reviewed Original ResearchConceptsChildhood adverse experiencesChildhood adversitySingle nucleotide polymorphismsFKBP5 polymorphismsAdverse experiencesAfrican AmericansPost-traumatic stress disorder symptomsChildhood adversity exposureLogistic regression analysisChildhood abusePost-traumatic stress disorderRisk of PTSDCortisol-binding affinityDepressive episodeLifetime PTSDFKBP5 genotypeHigh riskTT genotypeLower riskRecurrence riskGlucocorticoid receptorAlcohol dependenceFKBP5 locusStress disorderFKBP5
2009
Association study of DTNBP1 with schizophrenia in a US sample
Zuo L, Luo X, Kranzler HR, Lu L, Rosenheck RA, Cramer J, van Kammen DP, Erdos J, Charney DS, Krystal J, Gelernter J. Association study of DTNBP1 with schizophrenia in a US sample. Psychiatric Genetics 2009, 19: 292-304. PMID: 19862852, PMCID: PMC2771321, DOI: 10.1097/ypg.0b013e32832a50bc.Peer-Reviewed Original ResearchInteraction of Childhood Maltreatment with the Corticotropin-Releasing Hormone Receptor Gene: Effects on Hypothalamic-Pituitary-Adrenal Axis Reactivity
Tyrka AR, Price LH, Gelernter J, Schepker C, Anderson GM, Carpenter LL. Interaction of Childhood Maltreatment with the Corticotropin-Releasing Hormone Receptor Gene: Effects on Hypothalamic-Pituitary-Adrenal Axis Reactivity. Biological Psychiatry 2009, 66: 681-685. PMID: 19596121, PMCID: PMC2881567, DOI: 10.1016/j.biopsych.2009.05.012.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAdult Survivors of Child AbuseCorticotropin-Releasing HormoneDepressionDexamethasoneFemaleGenotypeHumansHydrocortisoneHypothalamo-Hypophyseal SystemLinear ModelsLinkage DisequilibriumMaleMiddle AgedPituitary-Adrenal SystemPolymorphism, GeneticReceptors, Corticotropin-Releasing HormoneStress, PsychologicalSurveys and QuestionnairesYoung AdultConceptsDEX/CRH testAdrenal (HPA) axis reactivityEarly life stressCortisol responseCRH testAxis reactivityDexamethasone/corticotropin-releasing hormone testCorticotropin-releasing hormone testChildhood maltreatmentCRHR1 polymorphismsHormone receptor geneHPA axis activationLife stressReceptor geneElevated cortisol responseDevelopment of moodChildhood Trauma QuestionnaireHormone testAxis activationHypothalamic-PituitaryNon-Hispanic adultsBlood samplesGG genotypeAdult depressionAnxiety disorders
2008
Interaction between Two Independent CNR1 Variants Increases Risk for Cocaine Dependence in European Americans: A Replication Study in Family-Based Sample and Population-Based Sample
Zuo L, Kranzler HR, Luo X, Yang BZ, Weiss R, Brady K, Poling J, Farrer L, Gelernter J. Interaction between Two Independent CNR1 Variants Increases Risk for Cocaine Dependence in European Americans: A Replication Study in Family-Based Sample and Population-Based Sample. Neuropsychopharmacology 2008, 34: 1504-1513. PMID: 19052543, PMCID: PMC2879626, DOI: 10.1038/npp.2008.206.Peer-Reviewed Original ResearchBlack or African AmericanCase-Control StudiesCluster AnalysisCocaineCocaine-Related DisordersFamilyGenetic Predisposition to DiseaseHaplotypesHumansLinkage DisequilibriumParanoid DisordersPolymorphism, Single NucleotideReceptor, Cannabinoid, CB1Regression AnalysisSequence Analysis, DNAUnited StatesWhite PeopleInfluence of Vascular Endothelial Growth Factor Variation on Human Hippocampus Morphology
Blumberg HP, Wang F, Chepenik LG, Kalmar JH, Edmiston E, Duman RS, Gelernter J. Influence of Vascular Endothelial Growth Factor Variation on Human Hippocampus Morphology. Biological Psychiatry 2008, 64: 901-903. PMID: 18707678, PMCID: PMC2649728, DOI: 10.1016/j.biopsych.2008.07.003.Peer-Reviewed Original Research
2007
Interpopulation linkage disequilibrium patterns of GABRA2 and GABRG1 genes at the GABA cluster locus on human chromosome 4
Ittiwut C, Listman J, Mutirangura A, Malison R, Covault J, Kranzler HR, Sughondhabirom A, Thavichachart N, Gelernter J. Interpopulation linkage disequilibrium patterns of GABRA2 and GABRG1 genes at the GABA cluster locus on human chromosome 4. Genomics 2007, 91: 61-69. PMID: 17976953, PMCID: PMC2709929, DOI: 10.1016/j.ygeno.2007.08.007.Peer-Reviewed Original ResearchConceptsLinkage disequilibrium patternsDisequilibrium patternsHuman chromosome 4Intergenic distancesIntergenic regionHaplotype block structureChromosome 4Haplotype structureLD blocksFunctional variantsGamma 1 subunitChromosome 4pHigh LDGABRA2 locusGenetic associationGenesLociDifferent populationsAlpha 2GABRA2KbSubunitsPopulationReported associationsGABRG1