2020
Characterizing the effect of background selection on the polygenicity of brain-related traits
Wendt FR, Pathak GA, Overstreet C, Tylee DS, Gelernter J, Atkinson EG, Polimanti R. Characterizing the effect of background selection on the polygenicity of brain-related traits. Genomics 2020, 113: 111-119. PMID: 33278486, PMCID: PMC7855394, DOI: 10.1016/j.ygeno.2020.11.032.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesBrain-related traitsGWAS of schizophreniaTrait-associated lociLocus effect sizesSubset of traitsGenotype networksGenetic architectureIntolerant regionsBrain-related phenotypesBackground selectionNatural selectionEvolutionary pressurePositive selectionSNP heritabilityLocal ancestryAssociation studiesTraitsFunctional significanceLociPolygenicityBinary annotationPhenotypeRisk allelesSize variance
2018
Genome-wide Association Study Identifies a Regulatory Variant of RGMA Associated With Opioid Dependence in European Americans
Cheng Z, Zhou H, Sherva R, Farrer LA, Kranzler HR, Gelernter J. Genome-wide Association Study Identifies a Regulatory Variant of RGMA Associated With Opioid Dependence in European Americans. Biological Psychiatry 2018, 84: 762-770. PMID: 29478698, PMCID: PMC6041180, DOI: 10.1016/j.biopsych.2017.12.016.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHomologous mouse geneMouse geneAxon guidance proteinRegulatory variantsCoexpression analysisOpioid dependenceTranscript variantsGenetic studiesChromosome 15Guidance proteinsRNA expressionNominal significanceMessenger RNA expressionGenesRepulsive guidance molecule AHigh expressionRGMaRisk allelesChronic morphine injectionDSM-IV diagnosisExpressionNew leadsMorphine injection
2017
Genetic 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 dependenceWidespread signatures of positive selection in common risk alleles associated to autism spectrum disorder
Polimanti R, Gelernter J. Widespread signatures of positive selection in common risk alleles associated to autism spectrum disorder. PLOS Genetics 2017, 13: e1006618. PMID: 28187187, PMCID: PMC5328401, DOI: 10.1371/journal.pgen.1006618.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAttention Deficit Disorder with HyperactivityAutism Spectrum DisorderBipolar DisorderBrainComputational BiologyDepressive Disorder, MajorGene Expression ProfilingGene OntologyGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyGenomicsHumansPituitary GlandPolymorphism, Single NucleotideRisk FactorsSchizophreniaTranscriptomeConceptsPositive selectionGene Ontology enrichmentGene expression enrichmentPrevious genetic studiesGWAS summary statisticsNervous system developmentCommon risk allelesPsychiatric Genomics ConsortiumSystems geneticsOntology enrichmentRisk allelesSynapse organizationWidespread signaturesEvolutionary processesGenetic studiesGenomics ConsortiumGWASHuman evolutionAllelesIncomplete selectionEffect directionMinor alleleComplete selectionEnrichmentSummary statistics
2016
Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women
Polimanti R, Kranzler HR, Gelernter J. Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women. Neuropsychopharmacology 2016, 41: 2688-2696. PMID: 27187070, PMCID: PMC5026736, DOI: 10.1038/npp.2016.72.Peer-Reviewed Original ResearchConceptsHealth initiativesRisk allelesSocioeconomic statusPhenome-wide association studyWomen's Health InitiativeMetabolism-related mechanismsMedication useLung cancerTobacco useDietary habitsSmoking behaviorNicotine useReproductive historyReproductive healthSuggestive findingsAlcohol useAnthropometric characteristicsMental healthHealth conditionsMetabolic conditionsCausative relationshipAssociation studiesDrinking behaviorADH1BAssociationA protocadherin gene cluster regulatory variant is associated with nicotine withdrawal and the urge to smoke
Jensen KP, Smith AH, Herman AI, Farrer LA, Kranzler HR, Sofuoglu M, Gelernter J. A protocadherin gene cluster regulatory variant is associated with nicotine withdrawal and the urge to smoke. Molecular Psychiatry 2016, 22: 242-249. PMID: 27067016, PMCID: PMC5390815, DOI: 10.1038/mp.2016.43.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlack or African AmericanCadherinsDiagnostic and Statistical Manual of Mental DisordersFemaleGene Expression RegulationGenome-Wide Association StudyHumansMaleMultigene FamilyNicotinePolymorphism, Single NucleotideProtocadherinsRecurrenceSmokingSmoking CessationSubstance Withdrawal SyndromeTobacco Use DisorderWhite PeopleConceptsNicotine withdrawalSingle nucleotide polymorphismsNovel smoking cessation treatmentsAfrican AmericansSmoking cessation treatmentNicotine withdrawal symptomsOvernight smoking abstinenceEuropean American smokersFrontal cortex tissueΓ geneCessation treatmentTobacco smokingSmoking abstinenceWithdrawal symptomsAbstinent smokersAmerican smokersΓ gene expressionNicotine infusionSmoking urgesInfusion studiesSmokersMRNA expressionRisk allelesCortex tissueBrief questionnaire
2015
A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans
Jensen KP, DeVito EE, Herman AI, Valentine GW, Gelernter J, Sofuoglu M. A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans. Neuropsychopharmacology 2015, 40: 2813-2821. PMID: 25948103, PMCID: PMC4864657, DOI: 10.1038/npp.2015.131.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlood PressureCognition DisordersCotinineFemaleGenome-Wide Association StudyHeart RateHumansMaleMiddle AgedNerve Tissue ProteinsNeuropsychological TestsNicotineNicotinic AgonistsPolymorphism, Single NucleotideReceptors, NicotinicSmokingSubstance Withdrawal SyndromeSurveys and QuestionnairesConceptsAversive effectsHeavy smokingRisk allelesSmoking-related disordersAfrican American smokersCHRNA5-CHRNA3Doses of nicotineHigh nicotine doseNicotine administrationIntravenous doseNicotine effectsNicotine doseAmerican smokersWithdrawal severityOvernight abstinenceAcute responseAA subjectsCardiovascular reactivityCHRNB4 gene clusterNicotineEuropean AmericansAversive responsesAdministration sessionsSmokingCognitive performance
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
Genome-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
Increased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset Smokers
Hartz SM, Short SE, Saccone NL, Culverhouse R, Chen L, Schwantes-An TH, Coon H, Han Y, Stephens SH, Sun J, Chen X, Ducci F, Dueker N, Franceschini N, Frank J, Geller F, Gubjartsson D, Hansel NN, Jiang C, Keskitalo-Vuokko K, Liu Z, Lyytikäinen LP, Michel M, Rawal R, Rosenberger A, Scheet P, Shaffer JR, Teumer A, Thompson JR, Vink JM, Vogelzangs N, Wenzlaff AS, Wheeler W, Xiao X, Yang BZ, Aggen SH, Balmforth AJ, Baumeister SE, Beaty T, Bennett S, Bergen AW, Boyd HA, Broms U, Campbell H, Chatterjee N, Chen J, Cheng YC, Cichon S, Couper D, Cucca F, Dick DM, Foroud T, Furberg H, Giegling I, Gu F, Hall AS, Hällfors J, Han S, Hartmann AM, Hayward C, Heikkilä K, Hewitt JK, Hottenga JJ, Jensen MK, Jousilahti P, Kaakinen M, Kittner SJ, Konte B, Korhonen T, Landi MT, Laatikainen T, Leppert M, Levy SM, Mathias RA, McNeil DW, Medland SE, Montgomery GW, Muley T, Murray T, Nauck M, North K, Pergadia M, Polasek O, Ramos EM, Ripatti S, Risch A, Ruczinski I, Rudan I, Salomaa V, Schlessinger D, Styrkársdóttir U, Terracciano A, Uda M, Willemsen G, Wu X, Abecasis G, Barnes K, Bickeböller H, Boerwinkle E, Boomsma DI, Caporaso N, Duan J, Edenberg HJ, Francks C, Gejman PV, Gelernter J, Grabe HJ, Hops H, Jarvelin MR, Viikari J, Kähönen M, Kendler KS, Lehtimäki T, Levinson DF, Marazita ML, Marchini J, Melbye M, Mitchell BD, Murray JC, Nöthen MM, Penninx BW, Raitakari O, Rietschel M, Rujescu D, Samani NJ, Sanders AR, Schwartz AG, Shete S, Shi J, Spitz M, Stefansson K, Swan GE, Thorgeirsson T, Völzke H, Wei Q, Wichmann H, Amos CI, Breslau N, Cannon DS, Ehringer M, Grucza R, Hatsukami D, Heath A, Johnson EO, Kaprio J, Madden P, Martin NG, Stevens VL, Stitzel JA, Weiss RB, Kraft P, Bierut LJ. Increased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset Smokers. JAMA Psychiatry 2012, 69: 854-860. PMID: 22868939, PMCID: PMC3482121, DOI: 10.1001/archgenpsychiatry.2012.124.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdolescent DevelopmentAdultAge of OnsetEuropeFemaleGene-Environment InteractionGenetic Association StudiesGenetic Predisposition to DiseaseHumansMaleNerve Tissue ProteinsNicotinePolymorphism, Single NucleotideReceptors, NicotinicSeverity of Illness IndexSmokingTobacco Use DisorderConceptsEarly-onset smokersLate-onset smokersHeavy smokersRisk allelesGenetic vulnerabilityRs16969968 genotypeLight smokersLight smokingRegular smokingSmokersSmokingMeta-AnalysisLogistic regressionRs16969968Single nucleotide polymorphismsAgeNonsynonymous single nucleotide polymorphismsCHRNA5Recent studiesAvailable genetic studiesAssociationSample sizeStudyCigarettesGenetic studies
2011
Components of Cross-Frequency Modulation in Health and Disease
Allen EA, Liu J, Kiehl KA, Gelernter J, Pearlson GD, Perrone-Bizzozero NI, Calhoun VD. Components of Cross-Frequency Modulation in Health and Disease. Frontiers In Systems Neuroscience 2011, 5: 59. PMID: 21808609, PMCID: PMC3139214, DOI: 10.3389/fnsys.2011.00059.Peer-Reviewed Original ResearchHealthy controlsSchizophrenia patientsCross-frequency modulationAbnormal temporal integrationDopamine D2 receptorsHigh-frequency activityAuditory oddball taskD2 receptorsCognitive deficitsFunctional connectivityPatientsRisk allelesGenetic polymorphismsΑ2 subunitFronto-temporal electrodesOddball taskEEG recordingsDiseaseReceptorsRisk lociExploratory analysisHealthTotal numberModulationPolymorphism
2009
A sequencing‐based survey of functional APAF1 alleles in a large sample of individuals with affective illness and population controls
Amin Z, Kanarek K, Krupitsky E, Walderhaug E, Ilomäki R, Blumberg H, Price LH, Bhagwagar Z, Carpenter LL, Tyrka AR, Magnusson A, Landrø NI, Zvartau E, Gelernter J, Epperson CN, Räsänen P, Siironen J, Lappalainen J. A sequencing‐based survey of functional APAF1 alleles in a large sample of individuals with affective illness and population controls. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2009, 153B: 332-335. PMID: 19455599, PMCID: PMC3580167, DOI: 10.1002/ajmg.b.30984.Peer-Reviewed Original Research