2023
Identifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study
Xu H, Toikumo S, Crist R, Glogowska K, Jinwala Z, Deak J, Justice A, Gelernter J, Johnson E, Kranzler H, Kember R. Identifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study. Addiction 2023, 118: 1942-1952. PMID: 37156939, PMCID: PMC10754226, DOI: 10.1111/add.16229.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSignificant single nucleotide polymorphismsSubstance use traitsMulti-trait analysisAssociation studiesGenetic architectureUse traitsGenome-wide significant single nucleotide polymorphismsProtein-protein interaction analysisTrait genetic architectureNumber of lociPolygenic risk scoresEuropean ancestry individualsNovel lociSingle nucleotide polymorphismsGenetic lociGWAS studiesLociMultiple related phenotypesNucleotide polymorphismsRelated phenotypesTraitsNovel associationsMTAgBiobank samples
2021
Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder
Johnson EC, Kapoor M, Hatoum AS, Zhou H, Polimanti R, Wendt FR, Walters RK, Lai D, Kember RL, Hartz S, Meyers JL, Peterson RE, Ripke S, Bigdeli TB, Fanous AH, Pato CN, Pato MT, Goate AM, Kranzler HR, O'Donovan MC, Walters JTR, Gelernter J, Edenberg HJ, Agrawal A. Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder. Psychological Medicine 2021, 53: 1196-1204. PMID: 34231451, PMCID: PMC8738774, DOI: 10.1017/s003329172100266x.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significant single nucleotide polymorphismsLarge-scale genome-wide association studiesSignificant single nucleotide polymorphismsIndependent genome-wide significant single nucleotide polymorphismsSignificant genetic correlationsGenomic regionsSingle nucleotide polymorphismsGene expressionGenetic covariancePleiotropic associationsAssociation studiesGenetic correlationsGenetic variantsNucleotide polymorphismsGenetic overlapDisorder-specific effectsAlcohol use disorderGenetic influencesGenesUse disordersPleiotropic effects of telomere length loci with brain morphology and brain tissue expression
Pathak GA, Wendt FR, Levey DF, Mecca AP, van Dyck CH, Gelernter J, Polimanti R. Pleiotropic effects of telomere length loci with brain morphology and brain tissue expression. Human Molecular Genetics 2021, 30: 1360-1370. PMID: 33831179, PMCID: PMC8255129, DOI: 10.1093/hmg/ddab102.Peer-Reviewed Original ResearchConceptsMethylation expressionGenetic variantsMapping gene functionTelomere lengthChromatin associationChromatin profilesGene functionGenetic colocalizationGene mappingGenomic relationshipsNeuropsychiatric traitsPleiotropic rolesDrug-gene interactionsCertain lociBrain tissue expressionGenesLociPleiotropic effectsBrain morphology measuresNucleotide polymorphismsAncestry populationsTissue expressionPhenotypic associationsPleiotropyAncestry groups
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
GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability
Pasman JA, Verweij KJH, Gerring Z, Stringer S, Sanchez-Roige S, Treur JL, Abdellaoui A, Nivard MG, Baselmans BML, Ong JS, Ip HF, van der Zee MD, Bartels M, Day FR, Fontanillas P, Elson SL, the 23andMe Research Team, de Wit H, Davis LK, MacKillop J, The Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Derringer JL, Branje SJT, Hartman CA, Heath AC, van Lier PAC, Madden PAF, Mägi R, Meeus W, Montgomery GW, Oldehinkel AJ, Pausova Z, Ramos-Quiroga JA, Paus T, Ribases M, Kaprio J, Boks MPM, Bell JT, Spector TD, Gelernter J, Boomsma DI, Martin NG, MacGregor S, Perry JRB, Palmer AA, Posthuma D, Munafò MR, Gillespie NA, Derks EM, Vink JM. GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability. Nature Neuroscience 2018, 21: 1161-1170. PMID: 30150663, PMCID: PMC6386176, DOI: 10.1038/s41593-018-0206-1.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overCell Adhesion MoleculesDatabases, GeneticFemaleGene Expression RegulationGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMaleMarijuana AbuseMendelian Randomization AnalysisMental HealthMiddle AgedPolymorphism, Single NucleotideRisk-TakingSchizophreniaYoung AdultConceptsGenome-wide association studiesNew risk lociLarge genome-wide association studiesGene-based testsIndependent single nucleotide polymorphismsDifferent expression levelsSignificant genetic correlationsHealth-related traitsSingle nucleotide polymorphismsEtiology of cannabisHeritable traitRisk lociSignificant genesAssociation studiesGenetic correlationsPsychiatric traitsGenetic variantsNucleotide polymorphismsGenetic overlapExpression levelsTraitsGenesNew insightsSchizophrenia riskMendelian randomization analysisGenome‐wide association meta‐analysis of age at first cannabis use
Minică CC, Verweij KJH, van der Most P, Mbarek H, Bernard M, van Eijk K, Lind PA, Liu MZ, Maciejewski DF, Palviainen T, Sánchez‐Mora C, Sherva R, Taylor M, Walters RK, Abdellaoui A, Bigdeli TB, Branje SJT, Brown SA, Casas M, Corley RP, Davey‐Smith G, Davies GE, Ehli EA, Farrer L, Fedko IO, Garcia‐Martínez I, Gordon SD, Hartman CA, Heath AC, Hickie IB, Hickman M, Hopfer CJ, Hottenga JJ, Kahn RS, Kaprio J, Korhonen T, Kranzler HR, Krauter K, van Lier P, Madden PAF, Medland SE, Neale MC, Meeus WHJ, Montgomery GW, Nolte IM, Oldehinkel AJ, Pausova Z, Ramos‐Quiroga J, Richarte V, Rose RJ, Shin J, Stallings MC, Wall TL, Ware JJ, Wright MJ, Zhao H, Koot HM, Paus T, Hewitt JK, Ribasés M, Loukola A, Boks MP, Snieder H, Munafò MR, Gelernter J, Boomsma DI, Martin NG, Gillespie NA, Vink JM, Derks EM. Genome‐wide association meta‐analysis of age at first cannabis use. Addiction 2018, 113: 2073-2086. PMID: 30003630, PMCID: PMC7087375, DOI: 10.1111/add.14368.Peer-Reviewed Original ResearchConceptsGenome-wide associationSingle nucleotide polymorphismsLinkage disequilibriumTwin-based heritabilityGene-based testsHigh linkage disequilibriumATPase geneWide associationATP2C2 geneChromosome 16Heritability analysisHeritability of ageGenetic variantsNucleotide polymorphismsDiscovery sampleHeritabilityGenesATP2C2Replication sampleEnvironmental factorsRole of calciumIdentified associationsFirst cannabis useFirst cannabisATP2B2Genome‐wide association study of cognitive flexibility assessed by the Wisconsin Card Sorting Test
Zhang H, Zhou H, Lencz T, Farrer LA, Kranzler HR, Gelernter J. Genome‐wide association study of cognitive flexibility assessed by the Wisconsin Card Sorting Test. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2018, 177: 511-519. PMID: 30134085, PMCID: PMC6110090, DOI: 10.1002/ajmg.b.32642.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSingle nucleotide polymorphismsAssociation studiesGenome-wide significant associationUbiquitin-specific peptidase 9Top single nucleotide polymorphismsComplex trait analysisEnriched gene setsPolygenic risk score analysisCommon single nucleotide polymorphismsGWS associationsSame effect directionGene setsPopulation variationProtein degradationNongenetic factorsTrait analysisChromosome 15Genetic correlationsRisk score analysisNucleotide polymorphismsEffect directionEuropean-American subjectsGenetic factorsBrain development
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
ALDH2 is associated to alcohol dependence and is the major genetic determinant of “daily maximum drinks” in a GWAS study of an isolated rural chinese sample
Quillen EE, Chen X, Almasy L, Yang F, He H, Li X, Wang X, Liu T, Hao W, Deng H, Kranzler HR, Gelernter J. ALDH2 is associated to alcohol dependence and is the major genetic determinant of “daily maximum drinks” in a GWAS study of an isolated rural chinese sample. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2013, 165: 103-110. PMID: 24277619, PMCID: PMC4149216, DOI: 10.1002/ajmg.b.32213.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsCandidate single nucleotide polymorphismsGenome-wide association analysisCandidate gene studiesPhenotypic variationMajor genetic determinantGWAS studiesHeritable phenotypesAldehyde dehydrogenase deficiencyGene studiesAssociation analysisRisk genesLinkage disequilibriumGenetic determinantsExtended pedigreesNucleotide polymorphismsNorthern Hunan ProvinceAD-related phenotypesPhenotypeALDH2Consumption rateCCDC63Genome-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 pathwaysMicroarrayGenome-wide Association Study Identifies New Susceptibility Loci for Posttraumatic Stress Disorder
Xie P, Kranzler HR, Yang C, Zhao H, Farrer LA, Gelernter J. Genome-wide Association Study Identifies New Susceptibility Loci for Posttraumatic Stress Disorder. Biological Psychiatry 2013, 74: 656-663. PMID: 23726511, PMCID: PMC3810148, DOI: 10.1016/j.biopsych.2013.04.013.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsGenome-wide significanceFirst intronGenome-wide association study analysisGenome-wide association analysisNew susceptibility lociCandidate gene association studiesNew susceptibility genesCommon risk allelesGene association studiesChromosome 7p12Association studiesAssociation analysisSusceptibility lociSusceptibility genesGenetic variantsNucleotide polymorphismsIntronsTLL1GenesLociRisk allelesGenetic factorsSignificant signalEuropean Americans
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 studyAssociation of COL25A1 with Comorbid Antisocial Personality Disorder and Substance Dependence
Li D, Zhao H, Kranzler HR, Oslin D, Anton RF, Farrer LA, Gelernter J. Association of COL25A1 with Comorbid Antisocial Personality Disorder and Substance Dependence. Biological Psychiatry 2012, 71: 733-740. PMID: 22297151, PMCID: PMC3548659, DOI: 10.1016/j.biopsych.2011.12.011.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsTwo-stage genetic association studyType II transmembrane proteinCase-control cohortAllelic p-valueAlpha 1 geneSame single nucleotide polymorphismIndependent case-control cohortsTransmembrane proteinTranscription factorsSNP mapGenetic association studiesEuropean American casesCandidate genesCOL25A1 geneAssociation studiesGenetic studiesFamily-based cohortChromosome 4q25GenesNucleotide polymorphismsCOL25A1Alzheimer's disease brainLong-term patternsDiscovery stage
2011
Variation 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 evidenceMediators
2009
Variation in RGS2 is Associated with Suicidal Ideation in an Epidemiological Study of Adults Exposed to the 2004 Florida Hurricanes
Amstadter AB, Koenen KC, Ruggiero KJ, Acierno R, Galea S, Kilpatrick DG, Gelernter J. Variation in RGS2 is Associated with Suicidal Ideation in an Epidemiological Study of Adults Exposed to the 2004 Florida Hurricanes. Archives Of Suicide Research 2009, 13: 349-357. PMID: 19813112, PMCID: PMC2760049, DOI: 10.1080/13811110903266541.Peer-Reviewed Original ResearchConceptsSuicidal ideationCurrent suicidal ideationEpidemiologic sampleRandom digit dial proceduresSingle nucleotide polymorphismsEpidemiological studiesBuccal DNA samplesFlorida hurricanesCurrent ideationIdeationAdultsHurricane exposureRs4606RGS2Social supportNucleotide polymorphismsRiskDNA samplesParticipantsSymptoms
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 polymorphismsMutation screen of the GAD2 gene and association study of alcoholism in three populations
Lappalainen J, Krupitsky E, Kranzler HR, Luo X, Remizov M, Pchelina S, Taraskina A, Zvartau E, Räsanen P, Makikyro T, Somberg LK, Krystal JH, Stein MB, Gelernter J. Mutation screen of the GAD2 gene and association study of alcoholism in three populations. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2006, 144B: 183-192. PMID: 17034009, DOI: 10.1002/ajmg.b.30377.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismBlack or African AmericanCase-Control StudiesDNA Mutational AnalysisExonsFemaleGene FrequencyGenetic Predisposition to DiseaseGenetic TestingGlutamate DecarboxylaseHispanic or LatinoHumansIsoenzymesLinkage DisequilibriumMaleMutationPolymorphism, Single NucleotideStudentsUnited StatesWhite PeopleConceptsSingle nucleotide polymorphismsGAD2 geneNon-synonymous polymorphismsAssociation studiesSequence variantsGamma-amino butyric acidGlutamate decarboxylase 2GenesMutation screenNucleotide polymorphismsAdditional populationsMajor enzymeG single nucleotide polymorphismPolymorphismG variantButyric acidPopulationVariantsEnzymeAdditional samplesRoleRussian malesVariationScreenDHPLCGENETIC 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
2004
NOTCH4 gene haplotype is associated with schizophrenia in African Americans
Luo X, Klempan TA, Lappalainen J, Rosenheck RA, Charney DS, Erdos J, van Kammen DP, Kranzler HR, Kennedy JL, Gelernter J. NOTCH4 gene haplotype is associated with schizophrenia in African Americans. Biological Psychiatry 2004, 55: 112-117. PMID: 14732589, DOI: 10.1016/s0006-3223(03)00588-2.Peer-Reviewed Original ResearchMeSH KeywordsAllelesBlack or African AmericanChi-Square DistributionCysteineDiagnostic and Statistical Manual of Mental DisordersFemaleGene FrequencyGenotypeGlycineHaplotypesHumansLinkage DisequilibriumMalePolymerase Chain ReactionPolymorphism, Single NucleotideProto-Oncogene ProteinsReceptor, Notch4Receptors, Cell SurfaceReceptors, NotchSchizophreniaThreonineConceptsHealthy control subjectsControl subjectsSingle nucleotide polymorphismsExact testSchizophrenia patientsAfrican AmericansFisher's exact testNOTCH4 locusChi-square testComparison of alleleEuropean-American subjectsPositive linkage disequilibriumAA subjectsPatientsSchizophreniaSpecific markersHaplotype frequenciesT associatesLinkage disequilibriumEA subjectsNOTCH4 geneSubjectsGene haplotypesAmerican subjectsNucleotide polymorphisms
2003
CALCYON gene variation, schizophrenia, and cocaine dependence
Luo X, Kranzler H, Lappalainen J, Rosenheck R, Charney D, Zuo L, Erdos J, van Kammen DP, Gelernter J. CALCYON gene variation, schizophrenia, and cocaine dependence. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2003, 125B: 25-30. PMID: 14755439, DOI: 10.1002/ajmg.b.20092.Peer-Reviewed Original ResearchConceptsCocaine dependenceSingle nucleotide polymorphismsExact testEA subjectsFisher's exact testSubstance use disordersCalcyon geneDopamine receptor-interacting proteinsComparison of alleleUse disordersEuropean-American subjectsControl groupAA subjectsSchizophreniaReceptor-interacting proteinHaplotype frequenciesPotential roleSpecific polymorphismsMotor controlGene variationSame haplotype blockGenetic variantsSubjectsNucleotide polymorphismsLinkage disequilibrium