2022
Phenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample
Kember RL, Hartwell EE, Xu H, Rotenberg J, Almasy L, Zhou H, Gelernter J, Kranzler HR. Phenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample. Biological Psychiatry 2022, 93: 536-545. PMID: 36273948, PMCID: PMC9931661, DOI: 10.1016/j.biopsych.2022.08.010.Peer-Reviewed Original ResearchConceptsSubstance use disordersAlcohol use disorderOpioid use disorderPolygenic risk scoresUse disordersCo-occurring psychiatric disordersComprehensive psychiatric interviewSemi-Structured AssessmentElectronic health recordsControl subjectsLow prevalencePsychiatric interviewRisk scorePsychiatric disordersPhenome-wide association analysisDrug dependenceEuropean individualsHealth recordsLifetime cannabisPhenome-wide association studyDisordersAfrican ancestry individualsDSM diagnosesPopulation sampleGenetic liability
2013
Deep resequencing of 17 glutamate system genes identifies rare variants in DISC1 and GRIN2B affecting risk of opioid dependence
Xie P, Kranzler HR, Krystal JH, Farrer LA, Zhao H, Gelernter J. Deep resequencing of 17 glutamate system genes identifies rare variants in DISC1 and GRIN2B affecting risk of opioid dependence. Addiction Biology 2013, 19: 955-964. PMID: 23855403, PMCID: PMC3815683, DOI: 10.1111/adb.12072.Peer-Reviewed Original ResearchConceptsOpioid dependenceSubstance dependenceRare variantsN-methyl-D-aspartate (NMDA) glutamate receptorsCo-occurring alcohol dependenceHealthy control subjectsControl subjectsNMDA systemOpioid abuseGlutamate receptorsSchizophrenia risk genesSD riskAlcohol dependenceSignificant associationCocaine dependenceAdditional subjectsOD riskRisk genesDISC1African AmericansFirst demonstrationCommon variantsRiskSubjectsMinor allele frequencyProfiling of Childhood Adversity-Associated DNA Methylation Changes in Alcoholic Patients and Healthy Controls
Zhang H, Wang F, Kranzler HR, Zhao H, Gelernter J. Profiling of Childhood Adversity-Associated DNA Methylation Changes in Alcoholic Patients and Healthy Controls. PLOS ONE 2013, 8: e65648. PMID: 23799031, PMCID: PMC3683055, DOI: 10.1371/journal.pone.0065648.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAlcoholismAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyBlack or African AmericanCase-Control StudiesChild AbuseCpG IslandsDNA MethylationEpigenesis, GeneticFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHumansMaleMiddle AgedNerve Tissue ProteinsNociceptin ReceptorPolymorphism, Single NucleotidePromoter Regions, GeneticReceptors, NicotinicReceptors, OpioidRetinal DehydrogenaseRGS ProteinsSequence Analysis, DNATranscription, GeneticWhite PeopleYoung AdultConceptsHealthy controlsAD patientsChildhood adversityDNA methylation changesIllumina GoldenGate methylation arrayPeripheral blood DNA methylation levelsBlood DNA methylation levelsAlcoholic patientsControl subjectsLinear regression analysisMethylation changesPatientsMethylation levelsPromoter regionEA casesBonferroni correctionRegression analysisP-valueAfrican AmericansOverall methylation levels
2011
ACSL6 Is Associated with the Number of Cigarettes Smoked and Its Expression Is Altered by Chronic Nicotine Exposure
Chen J, Brunzell DH, Jackson K, van der Vaart A, Z. J, Payne TJ, Sherva R, Farrer LA, Gejman P, Levinson DF, Holmans P, Aggen SH, Damaj I, Kuo PH, Webb BT, Anton R, Kranzler HR, Gelernter J, Li MD, Kendler KS, Chen X. ACSL6 Is Associated with the Number of Cigarettes Smoked and Its Expression Is Altered by Chronic Nicotine Exposure. PLOS ONE 2011, 6: e28790. PMID: 22205969, PMCID: PMC3243669, DOI: 10.1371/journal.pone.0028790.Peer-Reviewed Original ResearchConceptsACSL6 geneNicotine exposureNicotinic receptor antagonist mecamylaminePrevious schizophrenia studiesChronic nicotine exposureNicotinic receptor activationHippocampus of miceNumber of cigarettesOsmotic mini pumpsQuantity of cigarettesNon-schizophrenic subjectsAssociation of schizophreniaCigarettes SmokedHeavy smokersTobacco smokingNicotine administrationAntagonist mecamylamineControl subjectsIndependent associationTobacco dependenceFTND scoreHigh riskMini pumpsChronic exposureReceptor activation
2010
Genetic 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
2007
CNR1 Variation Modulates Risk for Drug and Alcohol Dependence
Zuo L, Kranzler HR, Luo X, Covault J, Gelernter J. CNR1 Variation Modulates Risk for Drug and Alcohol Dependence. Biological Psychiatry 2007, 62: 616-626. PMID: 17509535, DOI: 10.1016/j.biopsych.2006.12.004.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismBlack or African AmericanCase-Control StudiesChromosome MappingComorbidityFemaleGenetic MarkersGenetic Predisposition to DiseaseGenetic VariationGenotypeHumansMalePolymorphism, Single NucleotideReceptor, Cannabinoid, CB1Regression AnalysisRisk FactorsSubstance-Related DisordersWhite PeopleConceptsCannabinoid receptor 1Substance dependenceHealthy control subjectsHuman cannabinoid receptor 1Control subjectsSD patientsT genotypeProtective allelesAlcohol dependenceReceptor 1Disease riskModulate riskCNR1 geneCNR1 variationInitial reportCase-control sampleLarge case-control sampleRegression analysisRiskStrong genetic effectsMarkersSignificant interaction effectMultiple markersAncestry informative markersSNP8
2006
Brain derived neurotrophic factor (BDNF) gene variants and Alzheimer's disease, affective disorders, posttraumatic stress disorder, schizophrenia, and substance dependence
Zhang H, Ozbay F, Lappalainen J, Kranzler HR, van Dyck CH, Charney DS, Price LH, Southwick S, Yang B, Rasmussen A, Gelernter J. Brain derived neurotrophic factor (BDNF) gene variants and Alzheimer's disease, affective disorders, posttraumatic stress disorder, schizophrenia, and substance dependence. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2006, 141B: 387-393. PMID: 16649215, PMCID: PMC2567822, DOI: 10.1002/ajmg.b.30332.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAlzheimer DiseaseBrain-Derived Neurotrophic FactorChromatography, High Pressure LiquidDNA Mutational AnalysisFemaleGene FrequencyGenotypeHaplotypesHumansLinkage DisequilibriumLogistic ModelsMaleMiddle AgedMood DisordersPolymorphism, Single NucleotideSchizophreniaStress Disorders, Post-TraumaticSubstance-Related DisordersConceptsPosttraumatic stress disorderAffective disordersAlzheimer's diseaseSubstance dependenceGene variantsStress disorderBDNF gene variantsNormal control subjectsLogistic regression analysisAge of subjectsBDNF variantsNeurotrophic factorControl subjectsBDNF geneBDNF SNPsG genotypeEuropean-American subjectsG alleleDrug dependenceNeuropsychiatric disordersModest associationSchizophreniaDiseaseNovel gene variantsDisordersGENETIC 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
2005
Apolipoprotein E epsilon4 is associated with atrophy of the amygdala in Alzheimer's disease
Basso M, Gelernter J, Yang J, MacAvoy MG, Varma P, Bronen RA, van Dyck CH. Apolipoprotein E epsilon4 is associated with atrophy of the amygdala in Alzheimer's disease. Neurobiology Of Aging 2005, 27: 1416-1424. PMID: 16182410, DOI: 10.1016/j.neurobiolaging.2005.08.002.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAD patientsAPOE epsilon4AD groupImportant genetic risk factorApolipoprotein E epsilon4Regional brain atrophyAPOE epsilon4 alleleElderly control subjectsNormal elderly control subjectsGenetic risk factorsAmygdaloid volumesBrain atrophyControl subjectsEpsilon4 carriersRisk factorsEpsilon4 alleleHippocampal volumeEpsilon4 doseAnalysis of covarianceDisease severityPatientsEpsilon4AmygdalaAtrophyAssociation Between Alcoholism and γ‐Amino Butyric Acid α2 Receptor Subtype in a Russian Population
Lappalainen J, Krupitsky E, Remizov M, Pchelina S, Taraskina A, Zvartau E, Somberg LK, Covault J, Kranzler HR, Krystal JH, Gelernter J. Association Between Alcoholism and γ‐Amino Butyric Acid α2 Receptor Subtype in a Russian Population. Alcohol Clinical And Experimental Research 2005, 29: 493-498. PMID: 15834213, DOI: 10.1097/01.alc.0000158938.97464.90.Peer-Reviewed Original ResearchConceptsAlcohol-dependent menAlcohol dependenceUS populationSingle nucleotide polymorphismsReceptor subtypesGABRA2 single nucleotide polymorphismsAlpha2-receptor subtypesPopulation control subjectsΑ2-receptor subtypeAlcohol-dependent populationTight linkage disequilibriumControl subjectsReal-time PCRTrend-level associationIncrease riskLarge genetic studiesChi analysisSignificant association
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
1999
No association between D2 dopamine receptor (DRD2) “A” system alleles, or DRD2 haplotypes, and posttraumatic stress disorder
Gelernter J, Southwick S, Goodson S, Morgan A, Nagy L, Charney D. No association between D2 dopamine receptor (DRD2) “A” system alleles, or DRD2 haplotypes, and posttraumatic stress disorder. Biological Psychiatry 1999, 45: 620-625. PMID: 10088049, DOI: 10.1016/s0006-3223(98)00087-0.Peer-Reviewed Original Research
1989
Corpus callosum dimensions measured by magnetic resonance imaging in bipolar affective disorder and schizophrenia
Hauser P, Dauphinais I, Berrettini W, DeLisi L, Gelernter J, Post R. Corpus callosum dimensions measured by magnetic resonance imaging in bipolar affective disorder and schizophrenia. Biological Psychiatry 1989, 26: 659-668. PMID: 2804188, DOI: 10.1016/0006-3223(89)90100-5.Peer-Reviewed Original ResearchConceptsCerebral areasMagnetic resonance imaging (MRI) brain scansBipolar affective patientsNormal control subjectsBipolar affective disorderControl subjectsCallosal areaPsychiatric illnessCallosal regionsSchizophrenic patientsAffective patientsGender differencesAffective disordersControl groupBrain scansMale subjectsDiagnostic groupsSchizophrenic groupFemale subjectsTesla scannerMidsagittal sliceSignificant differencesPatientsCallosalGenu