2024
Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program
Verma A, Huffman J, Rodriguez A, Conery M, Liu M, Ho Y, Kim Y, Heise D, Guare L, Panickan V, Garcon H, Linares F, Costa L, Goethert I, Tipton R, Honerlaw J, Davies L, Whitbourne S, Cohen J, Posner D, Sangar R, Murray M, Wang X, Dochtermann D, Devineni P, Shi Y, Nandi T, Assimes T, Brunette C, Carroll R, Clifford R, Duvall S, Gelernter J, Hung A, Iyengar S, Joseph J, Kember R, Kranzler H, Kripke C, Levey D, Luoh S, Merritt V, Overstreet C, Deak J, Grant S, Polimanti R, Roussos P, Shakt G, Sun Y, Tsao N, Venkatesh S, Voloudakis G, Justice A, Begoli E, Ramoni R, Tourassi G, Pyarajan S, Tsao P, O'Donnell C, Muralidhar S, Moser J, Casas J, Bick A, Zhou W, Cai T, Voight B, Cho K, Gaziano J, Madduri R, Damrauer S, Liao K. Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. Science 2024, 385: eadj1182. PMID: 39024449, DOI: 10.1126/science.adj1182.Peer-Reviewed Original ResearchConceptsMillion Veteran ProgramNon-European populationsVeteran ProgramGenetic architectureAtlas of genetic associationsVeterans Affairs Million Veteran ProgramVA Million Veteran ProgramGenomic risk lociGenome-wide associationHuman genetic studiesHealth disparitiesUnited States veteransCausal variantsRisk lociGenetic insightsGenetic studiesGenetic associationGenetic causeStates veteransDiverse populationsDisease factorsLack of inclusionLongitudinal studyParticipantsTraits
2021
Genome-wide association study of stimulant dependence
Cox J, Sherva R, Wetherill L, Foroud T, Edenberg HJ, Kranzler HR, Gelernter J, Farrer LA. Genome-wide association study of stimulant dependence. Translational Psychiatry 2021, 11: 363. PMID: 34226506, PMCID: PMC8257618, DOI: 10.1038/s41398-021-01440-5.Peer-Reviewed Original ResearchConceptsStimulant dependenceAssociation studiesVoltage-gated channel proteinsGenome-wide association studiesNicotinic acetylcholine receptor genesTop GWAS signalsUse disordersAcetylcholine receptor genesWide association studyGWAS signalsSubstance use disordersEuropean ancestry subjectsNovel genesCocaine use disorderUsers of cocaineChannel proteinsGenetic studiesSpecific genetic factorsGenetics of AlcoholismSignificant pleiotropy
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
Widespread 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
2015
The genetics of alcohol dependence: Twin and SNP‐based heritability, and genome‐wide association study based on AUDIT scores
Mbarek H, Milaneschi Y, Fedko IO, Hottenga JJ, de Moor MH, Jansen R, Gelernter J, Sherva R, Willemsen G, Boomsma DI, Penninx BW, Vink JM. The genetics of alcohol dependence: Twin and SNP‐based heritability, and genome‐wide association study based on AUDIT scores. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2015, 168: 739-748. PMID: 26365420, DOI: 10.1002/ajmg.b.32379.Peer-Reviewed Original ResearchConceptsGenome-wide complex trait analysisWide association studySNP effect concordance analysisAssociation studiesTop hitsSNP-based heritabilityTwin-based heritabilityPrevious genetic studiesComplex trait analysisFirst GWASGenetic basisTrait analysisGenetic studiesCommon SNPsSNP effectsPrevious GWASGWASLarge-scale biobanksHeritabilityHeritability estimatesEvidence of CNIH3 involvement in opioid dependence
Nelson EC, Agrawal A, Heath AC, Bogdan R, Sherva R, Zhang B, Al-Hasani R, Bruchas MR, Chou YL, Demers CH, Carey CE, Conley ED, Fakira AK, Farrer LA, Goate A, Gordon S, Henders AK, Hesselbrock V, Kapoor M, Lynskey MT, Madden PA, Moron JA, Rice JP, Saccone NL, Schwab SG, Shand FL, Todorov AA, Wallace L, Wang T, Wray NR, Zhou X, Degenhardt L, Martin NG, Hariri AR, Kranzler HR, Gelernter J, Bierut LJ, Clark DJ, Montgomery GW. Evidence of CNIH3 involvement in opioid dependence. Molecular Psychiatry 2015, 21: 608-614. PMID: 26239289, PMCID: PMC4740268, DOI: 10.1038/mp.2015.102.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsGenome-wide association studiesComputational genetic analysisEpigenetic annotationsGenetic analysisAssociation studiesGenetic studiesStudy of AddictionVivo functionalityMouse strainsOpioid dependenceNeurogenetics StudySevere addictive disordersΑ-aminoGenesOpioid misusersGeneticsCnih3SNPsDuke Neurogenetics StudyHaplotypesPhenotypeA alleleAllelesFetal brain
2013
The Role and Challenges of Exome Sequencing in Studies of Human Diseases
Wang Z, Liu X, Yang BZ, Gelernter J. The Role and Challenges of Exome Sequencing in Studies of Human Diseases. Frontiers In Genetics 2013, 4: 160. PMID: 24032039, PMCID: PMC3752524, DOI: 10.3389/fgene.2013.00160.Peer-Reviewed Original ResearchHuman diseasesSequencing dataExome sequencingGenetic studiesProtein-coding portionNext-generation sequencing technologiesLow-frequency variantsComplex traitsExome sequencing dataHuman genomeSequencing technologiesExonic regionsTarget enrichmentFrequency variantsMendelian disordersSequencingTargeted sequencingVariant callsTarget regionRare variantsGenotype concordanceVariantsGenomeRecent advancesOverall consistency rate
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 studiesLinkage 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
Empirically derived subtypes of opioid use and related behaviors
Chan G, Gelernter J, Oslin D, Farrer L, Kranzler HR. Empirically derived subtypes of opioid use and related behaviors. Addiction 2011, 106: 1146-1154. PMID: 21306596, PMCID: PMC3164489, DOI: 10.1111/j.1360-0443.2011.03390.x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge of OnsetAgedAnalgesics, OpioidChildCluster AnalysisComorbidityDiagnostic and Statistical Manual of Mental DisordersFamily HealthFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHumansInterview, PsychologicalMaleMental DisordersMiddle AgedOpioid-Related DisordersPhenotypePrevalenceSiblingsSubstance Abuse, IntravenousUnited StatesYoung AdultConceptsOpioid usePsychiatric disordersHomogeneous subtypesRelated behaviorsSemi-Structured AssessmentGeneral community sampleOpioid dependenceMedical historyPrevalence ratesCocaine dependenceDrug dependenceSubtypesParticipant demographicsSubstance useCase-control genetic studyDemographicsDisordersCommunity sampleGenetic studies
2010
Identification of population substructure among Jews using STR markers and dependence on reference populations included
Listman JB, Hasin D, Kranzler HR, Malison RT, Mutirangura A, Sughondhabirom A, Aharonovich E, Spivak B, Gelernter J. Identification of population substructure among Jews using STR markers and dependence on reference populations included. BMC Genomic Data 2010, 11: 48. PMID: 20546593, PMCID: PMC2896335, DOI: 10.1186/1471-2156-11-48.Peer-Reviewed Original ResearchConceptsAssociation studiesPopulation substructureGenetic historyPopulation genetic historyMajor continental populationsSTR markersFuture genetic studiesProportion of ancestryChromosomal dataContinental populationsMitochondrial DNAPopulation structureParental populationsMarker choiceRelated populationsGenetic signaturesGenetic studiesAutosomal STR markersGenetic componentSTR panelNon-Ashkenazi Jewish populationsAsian clusterPopulation informationFuture investigationsPopulation
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