Featured Publications
Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications
Levey D, Galimberti M, Deak J, Wendt F, Bhattacharya A, Koller D, Harrington K, Quaden R, Johnson E, Gupta P, Biradar M, Lam M, Cooke M, Rajagopal V, Empke S, Zhou H, Nunez Y, Kranzler H, Edenberg H, Agrawal A, Smoller J, Lencz T, Hougaard D, Børglum A, Demontis D, Gaziano J, Gandal M, Polimanti R, Stein M, Gelernter J. Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications. Nature Genetics 2023, 55: 2094-2103. PMID: 37985822, PMCID: PMC10703690, DOI: 10.1038/s41588-023-01563-z.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphism-based heritabilityMulti-ancestry genome-wide association studyAssociation studiesMillion Veteran ProgramGenome-wide association studiesWide significant lociWide association studySignificant lociReference panelSmall populationDisease biologyAncestryAmerican ancestryHeritabilityVeteran ProgramNumerous medical comorbiditiesLung cancer riskRelationship analysisLociBiologyPublic health implicationsEast AsiansPublic health consequencesMedical comorbiditiesCigarette smokingGenome-wide association studies and cross-population meta-analyses investigating short and long sleep duration
Austin-Zimmerman I, Levey D, Giannakopoulou O, Deak J, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Concato J, Buysse D, Gaziano J, Gottlieb D, Polimanti R, Stein M, Bramon E, Gelernter J. Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration. Nature Communications 2023, 14: 6059. PMID: 37770476, PMCID: PMC10539313, DOI: 10.1038/s41467-023-41249-y.Peer-Reviewed Original ResearchConceptsAssociation studiesGenome-wide association studiesGenetic correlationsWide association studyLinkage disequilibrium scorePositive genetic correlationSleep traitsIndependent lociMillion Veteran ProgramTraitsAncestryUK BiobankVeteran ProgramMendelian randomisationLociHeritabilitySNPsPhenotypeEast AsiansSimilar patternCardiometabolic phenotypesGenome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program
Stein MB, Levey DF, Cheng Z, Wendt FR, Harrington K, Pathak GA, Cho K, Quaden R, Radhakrishnan K, Girgenti MJ, Ho YA, Posner D, Aslan M, Duman RS, Zhao H, Polimanti R, Concato J, Gelernter J. Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program. Nature Genetics 2021, 53: 174-184. PMID: 33510476, PMCID: PMC7972521, DOI: 10.1038/s41588-020-00767-x.Peer-Reviewed Original ResearchConceptsGenome-wide association analysisAssociation analysisMillion Veteran ProgramGenomic structural equation modelingSignificant lociGenetic varianceGene expressionDrug repositioning candidatesBiological coherenceVeteran ProgramMultiple testing correctionSymptom phenotypeLociRepositioning candidatesAfrican ancestryHeritabilityPhenotypeAncestryExpressionPTSD symptom factorsRegionSubdomainsEnrichmentGenome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits
Zhou H, Sealock JM, Sanchez-Roige S, Clarke TK, Levey DF, Cheng Z, Li B, Polimanti R, Kember RL, Smith RV, Thygesen JH, Morgan MY, Atkinson SR, Thursz MR, Nyegaard M, Mattheisen M, Børglum AD, Johnson EC, Justice AC, Palmer AA, McQuillin A, Davis LK, Edenberg HJ, Agrawal A, Kranzler HR, Gelernter J. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nature Neuroscience 2020, 23: 809-818. PMID: 32451486, PMCID: PMC7485556, DOI: 10.1038/s41593-020-0643-5.Peer-Reviewed Original ResearchConceptsRegulatory genomic regionsGenome-wide association studiesNovel risk lociEuropean ancestry individualsPolygenic risk score analysisIndependent risk variantsGenetic architectureGenomic regionsRisk lociAssociation studiesGenetic relationshipsRisk genesGenetic correlationsPsychiatric traitsRisk variantsRisk score analysisTraitsGenetic heritabilityYields insightsBiobank samplesMendelian randomizationGenesLociBiologyHeritability
2023
Genetic Decomposition of the Heritable Component of Reported Childhood Maltreatment
Kuile A, Hübel C, Cheesman R, Coleman J, Peel A, Levey D, Stein M, Gelernter J, Rayner C, Eley T, Breen G. Genetic Decomposition of the Heritable Component of Reported Childhood Maltreatment. Biological Psychiatry Global Open Science 2023, 3: 716-724. PMID: 37881567, PMCID: PMC10593925, DOI: 10.1016/j.bpsgos.2023.03.003.Peer-Reviewed Original ResearchGenetic componentGenomic structural equationGenome-wide association study summary statisticsCommon genetic variantsResidual genetic varianceGeneral risk toleranceGenetic variancePutative traitsHeritable componentBehavioral traitsGenetic correlationsTraitsGenetic variantsHeritable characteristicsHeritable factorsHeritabilityEnvironmental factorsDecades of researchGenetic influencesSummary statisticsPhenotype
2022
Sex-Specific Genetic and Transcriptomic Liability to Neuroticism
Wendt FR, Pathak GA, Singh K, Stein MB, Koenen KC, Krystal JH, Gelernter J, Davis LK, Polimanti R. Sex-Specific Genetic and Transcriptomic Liability to Neuroticism. Biological Psychiatry 2022, 93: 243-252. PMID: 36244801, PMCID: PMC10508260, DOI: 10.1016/j.biopsych.2022.07.019.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesTranscriptomic profilesAssociation studiesSingle nucleotide polymorphism heritabilityGene expression variationGenome-wide significanceSex-specific geneticChromosomal variationTranscriptomic changesRisk lociExpression variationBiological processesMolecular pathwaysLociPolygenic associationSex-specific effectsGenetic correlatesPolygenic scoresUK BiobankGenetic riskNCOA6GeneticsHeritabilityPathwayFemales
2018
Genome‐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 analysis of insomnia disorder
Stein MB, McCarthy MJ, Chen CY, Jain S, Gelernter J, He F, Heeringa SG, Kessler RC, Nock MK, Ripke S, Sun X, Wynn GH, Smoller JW, Ursano RJ. Genome-wide analysis of insomnia disorder. Molecular Psychiatry 2018, 23: 2238-2250. PMID: 29520036, PMCID: PMC6129221, DOI: 10.1038/s41380-018-0033-5.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlack or African AmericanCohort StudiesDepressive Disorder, MajorDiabetes Mellitus, Type 2FemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHispanic or LatinoHumansMaleMilitary PersonnelMultifactorial InheritancePolymorphism, Single NucleotideRisk FactorsSleep Initiation and Maintenance DisordersWhite PeopleYoung AdultConceptsGenome-wide association studiesAncestral groupsGenome-wide significant lociGenome-wide analysisGene-based associationSignificant gene-based associationsSleep-related traitsGenetic risk variantsSignificant lociChr 7Heritable basisChr 9Association studiesRisk variantsGenetic contributionLociUK BiobankMetabolic diseasesRFX3Genetic riskTraitsHeritabilityPolygenic riskTwin studiesDeleterious health effects
2017
Genome-wide association study identifies a novel locus for cannabis dependence
Agrawal A, Chou YL, Carey CE, Baranger DAA, Zhang B, Sherva R, Wetherill L, Kapoor M, Wang JC, Bertelsen S, Anokhin AP, Hesselbrock V, Kramer J, Lynskey MT, Meyers JL, Nurnberger JI, Rice JP, Tischfield J, Bierut LJ, Degenhardt L, Farrer LA, Gelernter J, Hariri AR, Heath AC, Kranzler HR, Madden PAF, Martin NG, Montgomery GW, Porjesz B, Wang T, Whitfield JB, Edenberg HJ, Foroud T, Goate AM, Bogdan R, Nelson EC. Genome-wide association study identifies a novel locus for cannabis dependence. Molecular Psychiatry 2017, 23: 1293-1302. PMID: 29112194, PMCID: PMC5938138, DOI: 10.1038/mp.2017.200.Peer-Reviewed Original ResearchMeSH KeywordsAdultAllelesBlack or African AmericanCannabisCase-Control StudiesChromosomes, Human, Pair 10Cohort StudiesFemaleGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMaleMarijuana AbuseMiddle AgedPhenotypePolymorphism, Single NucleotideWhite PeopleYoung AdultConceptsWide significant lociSingle nucleotide polymorphismsSignificant lociGenome-wide significant lociGenome-wide association study dataGenome-wide association studiesAssociation study dataCorrelated single-nucleotide polymorphismsNovel lociTranscription factorsChromosome 10Association studiesModerate heritabilityNovel regionLociBiological contributionEA college studentsMinor alleleEuropean descentH3K4me1Criterion countsHeritabilityPhenotypeEnhancerIndependent cohortLargest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability
Duncan LE, Ratanatharathorn A, Aiello AE, Almli LM, Amstadter AB, Ashley-Koch AE, Baker DG, Beckham JC, Bierut LJ, Bisson J, Bradley B, Chen CY, Dalvie S, Farrer LA, Galea S, Garrett ME, Gelernter JE, Guffanti G, Hauser MA, Johnson EO, Kessler RC, Kimbrel NA, King A, Koen N, Kranzler HR, Logue MW, Maihofer AX, Martin AR, Miller MW, Morey RA, Nugent NR, Rice JP, Ripke S, Roberts AL, Saccone NL, Smoller JW, Stein DJ, Stein MB, Sumner JA, Uddin M, Ursano RJ, Wildman DE, Yehuda R, Zhao H, Daly MJ, Liberzon I, Ressler KJ, Nievergelt CM, Koenen KC. Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability. Molecular Psychiatry 2017, 23: 666-673. PMID: 28439101, PMCID: PMC5696105, DOI: 10.1038/mp.2017.77.Peer-Reviewed Original ResearchMeSH KeywordsAdultBipolar DisorderBlack or African AmericanCase-Control StudiesDepressive Disorder, MajorFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedMultifactorial InheritancePolymorphism, Single NucleotideRisk FactorsSchizophreniaSex CharacteristicsSex FactorsStress Disorders, Post-TraumaticWhite PeopleConceptsSingle nucleotide polymorphismsRisk lociSNP-level summary statisticsGenomic data resourcesGenome-wide significanceMolecular genetic dataComplex genetic disorderPolygenic risk predictionGenetic dataAncestral diversityLarge GWASGenetic indicesDiverse phenotypesGenetic riskHeritability estimatesLociSummary statisticsGenetic disordersHeritabilityGenetic influencesGWASDiversityPhenotypeTransethnicStrong evidence
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 estimates
2014
Genome-Wide Association Study of Copy Number Variations (CNVs) with Opioid Dependence
Li D, Zhao H, Kranzler HR, Li MD, Jensen KP, Zayats T, Farrer LA, Gelernter J. Genome-Wide Association Study of Copy Number Variations (CNVs) with Opioid Dependence. Neuropsychopharmacology 2014, 40: 1016-1026. PMID: 25345593, PMCID: PMC4330517, DOI: 10.1038/npp.2014.290.Peer-Reviewed Original ResearchMeSH KeywordsAlpha CateninChromosome DeletionChromosome DisordersChromosomes, Human, Pair 18DNA Copy Number VariationsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansLeukocyte Common AntigensMaleMeta-Analysis as TopicOpioid-Related DisordersReceptor-Like Protein Tyrosine Phosphatases, Class 2ConceptsCopy number variationsAssociation studiesNumber variationsGenome-wide association studiesWide association studyUnique copy number variationsCommon copy number variationFirst GWASHarbor genesMissing heritabilityHuman genomeGenomic variationBiological importanceGenomeGenesGenetic risk factorsHeritabilitySubstance dependence riskGWASDuplicationDeletionReplicationPolymorphismVariationSmall proportion
2008
Substance dependence low-density whole genome association study in two distinct American populations
Yu Y, Kranzler HR, Panhuysen C, Weiss RD, Poling J, Farrer LA, Gelernter J. Substance dependence low-density whole genome association study in two distinct American populations. Human Genetics 2008, 123: 495. PMID: 18438686, PMCID: PMC3428017, DOI: 10.1007/s00439-008-0501-0.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphism (SNP) markersWhole-genome association studiesFuture candidate gene studiesGenome association studiesCandidate gene studiesPotential biological relevancePolymorphism markersGenetic basisAssociation studiesGenetic markersHigh heritabilityGene studiesCocaine-induced paranoiaBiological relevanceGenesComplex disorderNew hypothesisFamilyAmerican populationGeneticsHeritabilityMarkers