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 BiobankExpressionTENM2GNAI1GenesGeneticsVariantsPhenotypeA 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
2019
International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci
Nievergelt CM, Maihofer AX, Klengel T, Atkinson EG, Chen CY, Choi KW, Coleman JRI, Dalvie S, Duncan LE, Gelernter J, Levey DF, Logue MW, Polimanti R, Provost AC, Ratanatharathorn A, Stein MB, Torres K, Aiello AE, Almli LM, Amstadter AB, Andersen SB, Andreassen OA, Arbisi PA, Ashley-Koch AE, Austin SB, Avdibegovic E, Babić D, Bækvad-Hansen M, Baker DG, Beckham JC, Bierut LJ, Bisson JI, Boks MP, Bolger EA, Børglum AD, Bradley B, Brashear M, Breen G, Bryant RA, Bustamante AC, Bybjerg-Grauholm J, Calabrese JR, Caldas- de- Almeida J, Dale AM, Daly MJ, Daskalakis NP, Deckert J, Delahanty DL, Dennis MF, Disner SG, Domschke K, Dzubur-Kulenovic A, Erbes CR, Evans A, Farrer LA, Feeny NC, Flory JD, Forbes D, Franz CE, Galea S, Garrett ME, Gelaye B, Geuze E, Gillespie C, Uka AG, Gordon SD, Guffanti G, Hammamieh R, Harnal S, Hauser MA, Heath AC, Hemmings SMJ, Hougaard DM, Jakovljevic M, Jett M, Johnson EO, Jones I, Jovanovic T, Qin XJ, Junglen AG, Karstoft KI, Kaufman ML, Kessler RC, Khan A, Kimbrel NA, King AP, Koen N, Kranzler HR, Kremen WS, Lawford BR, Lebois LAM, Lewis CE, Linnstaedt SD, Lori A, Lugonja B, Luykx JJ, Lyons MJ, Maples-Keller J, Marmar C, Martin AR, Martin NG, Maurer D, Mavissakalian MR, McFarlane A, McGlinchey RE, McLaughlin KA, McLean SA, McLeay S, Mehta D, Milberg WP, Miller MW, Morey RA, Morris CP, Mors O, Mortensen PB, Neale BM, Nelson EC, Nordentoft M, Norman SB, O’Donnell M, Orcutt HK, Panizzon MS, Peters ES, Peterson AL, Peverill M, Pietrzak RH, Polusny MA, Rice JP, Ripke S, Risbrough VB, Roberts AL, Rothbaum AO, Rothbaum BO, Roy-Byrne P, Ruggiero K, Rung A, Rutten BPF, Saccone NL, Sanchez SE, Schijven D, Seedat S, Seligowski AV, Seng JS, Sheerin CM, Silove D, Smith AK, Smoller JW, Sponheim SR, Stein DJ, Stevens JS, Sumner JA, Teicher MH, Thompson WK, Trapido E, Uddin M, Ursano RJ, van den Heuvel LL, Van Hooff M, Vermetten E, Vinkers CH, Voisey J, Wang Y, Wang Z, Werge T, Williams MA, Williamson DE, Winternitz S, Wolf C, Wolf EJ, Wolff JD, Yehuda R, Young RM, Young KA, Zhao H, Zoellner LA, Liberzon I, Ressler KJ, Haas M, Koenen KC. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci. Nature Communications 2019, 10: 4558. PMID: 31594949, PMCID: PMC6783435, DOI: 10.1038/s41467-019-12576-w.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesDisease genesAssociation studiesGenome-wide significant lociAfrican-ancestry analysesNon-coding RNAsGenetic risk lociParkinson's disease genesEuropean ancestry populationsNovel genesSignificant lociGenetic variationSpecific lociRisk lociAdditional lociLociAncestry populationsCommon variantsHeritability estimatesGenesGWASRNABiologySNPsPARK2
2016
Review: DNA methylation and alcohol use disorders: Progress and challenges
Zhang H, Gelernter J. Review: DNA methylation and alcohol use disorders: Progress and challenges. American Journal On Addictions 2016, 26: 502-515. PMID: 27759945, PMCID: PMC6003819, DOI: 10.1111/ajad.12465.Peer-Reviewed Original ResearchConceptsDNA methylation changesDNA methylationMethylation changesGenome-wide DNA methylation studyGene expressionPromoter regionGlobal DNA methylation levelsDNA methylation profilesDNA methylation studiesDNA methylation levelsWidespread DNA methylationCandidate gene studiesEpigenetic mechanismsGenetic variationConsequences of AUDMethylation profilesMethylation studiesGene studiesMethylation levelsMethylationAUD subjectsGene-environment interactionsEnvironmental factorsInteractive effectsExpression
2014
Identification of methylation quantitative trait loci (mQTLs) influencing promoter DNA methylation of alcohol dependence risk genes
Zhang H, Wang F, Kranzler HR, Yang C, Xu H, Wang Z, Zhao H, Gelernter J. Identification of methylation quantitative trait loci (mQTLs) influencing promoter DNA methylation of alcohol dependence risk genes. Human Genetics 2014, 133: 1093-1104. PMID: 24889829, PMCID: PMC4127343, DOI: 10.1007/s00439-014-1452-2.Peer-Reviewed Original ResearchConceptsMethylation quantitative trait lociQuantitative trait lociDNA methylationTrait lociSignificant methylation quantitative trait lociSequence variantsRisk genesGene expression regulationGenome-wide association studiesGenome-wide genotype dataPromoter DNA methylationAD risk genesGene promoter regionExpression QTLsExpression regulationGenetic variationPromoter CpGsPromoter regionRare Human Nicotinic Acetylcholine Receptor α4 Subunit (CHRNA4) Variants Affect Expression and Function of High-Affinity Nicotinic Acetylcholine Receptors
McClure-Begley TD, Papke RL, Stone KL, Stokes C, Levy AD, Gelernter J, Xie P, Lindstrom J, Picciotto MR. Rare Human Nicotinic Acetylcholine Receptor α4 Subunit (CHRNA4) Variants Affect Expression and Function of High-Affinity Nicotinic Acetylcholine Receptors. Journal Of Pharmacology And Experimental Therapeutics 2014, 348: 410-420. PMID: 24385388, PMCID: PMC3935145, DOI: 10.1124/jpet.113.209767.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsRare variantsSingle amino acid substitutionLaevis oocytesAmino acid substitutionsΑ4β2 nAChRsAcetylcholine receptorsIntracellular interactomesHEK-293 cellsX. laevis oocytesProteomic analysisGenetic variationHuman α4β2 nAChRsXenopus laevis oocytesVoltage-clamp electrophysiologyNeuronal nicotinic acetylcholine receptorsHigh-affinity nicotinic acetylcholine receptorsSubcellular distributionAcid substitutionsΑ4 nAChR subunitCohort of smokersEffects of nicotineNAChR subunitsCommon variantsΑ4 nAChR
2007
Sequence variation and linkage disequilibrium in the GABA transporter-1 gene (SLC6A1) in five populations: implications for pharmacogenetic research
Hirunsatit R, Ilomäki R, Malison R, Räsänen P, Ilomäki E, Kranzler HR, Kosten T, Sughondhabirom A, Thavichachart N, Tangwongchai S, Listman J, Mutirangura A, Gelernter J, Lappalainen J. Sequence variation and linkage disequilibrium in the GABA transporter-1 gene (SLC6A1) in five populations: implications for pharmacogenetic research. BMC Genomic Data 2007, 8: 71. PMID: 17941974, PMCID: PMC2175509, DOI: 10.1186/1471-2156-8-71.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAsian PeopleBlack or African AmericanFinlandGABA Plasma Membrane Transport ProteinsGenetic Predisposition to DiseaseGenetic VariationHaplotypesHumansLinkage DisequilibriumPharmacogeneticsPolymorphism, Single NucleotidePromoter Regions, GeneticRecombination, GeneticSequence Analysis, DNAThailandWhite PeopleConceptsLinkage disequilibriumGenetic diversityVariable number tandem repeatHigh genetic diversityPopulation-specific variantsTransporter 1 geneProblematic genesRecombination hotspotsGenetic variationSequence variationContinental groupsIntronic regionsGenetic studiesLD blocksTandem repeatsNumber tandem repeatGAT-1 functionCandidate allelesLD patternsPopulation differencesNovel targetTag SNPsSuch variantsGenesTransporter 1
2006
Human clock, PER1 and PER2 polymorphisms: lack of association with cocaine dependence susceptibility and cocaine-induced paranoia
Malison RT, Kranzler HR, Yang BZ, Gelernter J. Human clock, PER1 and PER2 polymorphisms: lack of association with cocaine dependence susceptibility and cocaine-induced paranoia. Psychiatric Genetics 2006, 16: 245-249. PMID: 17106427, DOI: 10.1097/01.ypg.0000242198.59020.ca.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsNucleotide polymorphismsCircadian rhythm genesDrosophila melanogasterHuman orthologGenetic variationCocaine-induced paranoiaGenetic mechanismsRhythm genesGene single nucleotide polymorphismsPopulation comparisonsHuman clockLack of associationPotential involvementAllelic associationClinical featuresAllele frequenciesStimulant exposureBehavioral sensitizationLocomotor sensitizationPsychostimulant addictionDrug useClinical phenotypeCocaine dependencePER2 polymorphismsGENETIC STUDY: Analysis of variations in the tryptophan hydroxylase‐2 (TPH2) gene in cocaine dependence
Dahl JP, Cubells JF, Ray R, Weller AE, Lohoff FW, Ferraro TN, Oslin DW, Kampman KM, Dackis C, Tang Y, Gelernter J, Kranzler HR, O’Brien C, Berrettini WH. GENETIC STUDY: Analysis of variations in the tryptophan hydroxylase‐2 (TPH2) gene in cocaine dependence. Addiction Biology 2006, 11: 76-83. PMID: 16759340, DOI: 10.1111/j.1369-1600.2006.00005.x.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsCocaine dependenceTryptophan hydroxylase 2 geneTPH2 geneGenetic variationCase-control study designSerotonergic neurotransmitter systemCentral nervous systemSubstance use disordersGenesExact physiological mechanismsNucleotide polymorphismsAnalysis of variationPhysiological mechanismsControl subjectsBody of evidenceRisk factorsNeurotransmitter systemsUse disordersNervous systemStudy designAllele distributionPresent studyAfrican descentStudy associates
2000
Prediction of Dopamine Transporter Binding Availability by Genotype: A Preliminary Report
Jacobsen LK, Staley JK, Zoghbi SS, Seibyl JP, Kosten TR, Innis RB, Gelernter J. Prediction of Dopamine Transporter Binding Availability by Genotype: A Preliminary Report. American Journal Of Psychiatry 2000, 157: 1700-1703. PMID: 11007732, DOI: 10.1176/appi.ajp.157.10.1700.Peer-Reviewed Original ResearchMeSH KeywordsAdultCarrier ProteinsDNADopamineDopamine Plasma Membrane Transport ProteinsFemaleGenotypeHumansMaleMembrane GlycoproteinsMembrane Transport ProteinsMinisatellite RepeatsNerve Tissue ProteinsPolymerase Chain ReactionPolymorphism, GeneticSerotonin Plasma Membrane Transport ProteinsTomography, Emission-Computed, Single-Photon
1999
Population studies of polymorphisms of the serotonin transporter protein gene
Gelernter J, Cubells JF, Kidd JR, Pakstis AJ, Kidd KK. Population studies of polymorphisms of the serotonin transporter protein gene. American Journal Of Medical Genetics 1999, 88: 61-66. PMID: 10050969, DOI: 10.1002/(sici)1096-8628(19990205)88:1<61::aid-ajmg11>3.0.co;2-k.Peer-Reviewed Original ResearchConceptsAllele frequency variationImportant genetic variationTransporter protein geneSerotonin transporter protein geneProtein lociGenetic variationProtein geneAssociation studiesFunctional significancePopulation stratificationDepression-related phenotypesAllele frequenciesHaplotype frequenciesLociPolymorphismSLC6A4 polymorphismsGenesGlobal variationVNTR polymorphismPhenotypeDisequilibriumPopulationVariationPromoter polymorphismPopulation studies
1997
Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African- and European-American and Japanese populations and in alcohol-dependent subjects
Gelernter J, Kranzler H, Cubells J. Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African- and European-American and Japanese populations and in alcohol-dependent subjects. Human Genetics 1997, 101: 243-246. PMID: 9402979, DOI: 10.1007/s004390050624.Peer-Reviewed Original ResearchMeSH KeywordsAlcoholismAllelesAsian PeopleBlack PeopleCarrier ProteinsEuropeFemaleGene FrequencyHaplotypesHumansJapanLinkage DisequilibriumMaleMembrane GlycoproteinsMembrane Transport ProteinsNerve Tissue ProteinsPolymorphism, GeneticSerotonin Plasma Membrane Transport ProteinsUnited StatesWhite PeopleConceptsPairs of populationsRandom genetic driftHaplotype frequenciesAlters transcriptional activityDifferent behavioral adaptationsAllele frequenciesGenetic driftVariable number tandem repeatGenetic variationSequence polymorphismsTranscriptional activityPromoter regionBehavioral variationNeutral polymorphismsAssociation studiesTandem repeatsNumber tandem repeatSLC6A4 locusDepression-related traitsProtein allelesLinkage disequilibriumLociPopulation differencesPopulation stratificationExon 2