2022
Genetic variants associated with psychiatric disorders are enriched at epigenetically active sites in lymphoid cells
Lynall ME, Soskic B, Hayhurst J, Schwartzentruber J, Levey DF, Pathak GA, Polimanti R, Gelernter J, Stein MB, Trynka G, Clatworthy MR, Bullmore E. Genetic variants associated with psychiatric disorders are enriched at epigenetically active sites in lymphoid cells. Nature Communications 2022, 13: 6102. PMID: 36243721, PMCID: PMC9569335, DOI: 10.1038/s41467-022-33885-7.Peer-Reviewed Original ResearchConceptsMultiple psychiatric disordersPsychiatric disordersPsychiatric risk variantT cellsLymphoid cellsRisk variantsImmune cell subsetsMental health disordersMultiple organ systemsAdaptive immune systemCell subsetsImmune cellsHealth disordersMyeloid cellsImmune systemBrain tissueOrgan systemsSpecific disordersDisordersPathogenesisAbnormalitiesGenetic variantsCellsCD4VariantsMulti-trait genome-wide association study of opioid addiction: OPRM1 and beyond
Gaddis N, Mathur R, Marks J, Zhou L, Quach B, Waldrop A, Levran O, Agrawal A, Randesi M, Adelson M, Jeffries PW, Martin NG, Degenhardt L, Montgomery GW, Wetherill L, Lai D, Bucholz K, Foroud T, Porjesz B, Runarsdottir V, Tyrfingsson T, Einarsson G, Gudbjartsson DF, Webb BT, Crist RC, Kranzler HR, Sherva R, Zhou H, Hulse G, Wildenauer D, Kelty E, Attia J, Holliday EG, McEvoy M, Scott RJ, Schwab SG, Maher BS, Gruza R, Kreek MJ, Nelson EC, Thorgeirsson T, Stefansson K, Berrettini WH, Gelernter J, Edenberg HJ, Bierut L, Hancock DB, Johnson EO. Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond. Scientific Reports 2022, 12: 16873. PMID: 36207451, PMCID: PMC9546890, DOI: 10.1038/s41598-022-21003-y.Peer-Reviewed Original ResearchConceptsGenome-wide significant associationMulti-trait genome-wide association studyNovel genome-wide significant associationsGenome-wide association studiesGenomic structural equationGene-based analysisRelated traitsAssociation studiesGenetic correlationsEuropean ancestryA118G variantConsortium dataNew geneticsG variantGWASPPP6CLociPleiotropicGeneticsVariantsTraitsPhenotypeOA phenotypeFurinAncestry
2021
Ancestry may confound genetic machine learning: Candidate-gene prediction of opioid use disorder as an example
Hatoum AS, Wendt FR, Galimberti M, Polimanti R, Neale B, Kranzler HR, Gelernter J, Edenberg HJ, Agrawal A. Ancestry may confound genetic machine learning: Candidate-gene prediction of opioid use disorder as an example. Drug And Alcohol Dependence 2021, 229: 109115. PMID: 34710714, PMCID: PMC9358969, DOI: 10.1016/j.drugalcdep.2021.109115.Peer-Reviewed Original ResearchConceptsGenome-wide significant variantsCandidate gene predictionGenetic predictionRandom SNPsPolygenic traitRandom phenotypeCandidate SNPsSimulated phenotypesPsychiatric geneticsGenetic machineSignificant variantsBinary phenotypesCandidate variantsSNPsAncestryPhenotypeAllele frequenciesVariantsMachine learning modelsGenetic testsLearning model
2020
Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits
Quach BC, Bray MJ, Gaddis NC, Liu M, Palviainen T, Minica CC, Zellers S, Sherva R, Aliev F, Nothnagel M, Young KA, Marks JA, Young H, Carnes MU, Guo Y, Waldrop A, Sey NYA, Landi MT, McNeil DW, Drichel D, Farrer LA, Markunas CA, Vink JM, Hottenga JJ, Iacono WG, Kranzler HR, Saccone NL, Neale MC, Madden P, Rietschel M, Marazita ML, McGue M, Won H, Winterer G, Grucza R, Dick DM, Gelernter J, Caporaso NE, Baker TB, Boomsma DI, Kaprio J, Hokanson JE, Vrieze S, Bierut LJ, Johnson EO, Hancock DB. Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits. Nature Communications 2020, 11: 5562. PMID: 33144568, PMCID: PMC7642344, DOI: 10.1038/s41467-020-19265-z.Peer-Reviewed Original ResearchConceptsGenome-wide significant lociGenome-wide association studiesNearby gene expressionExpression of genesSmoking traitsGenetic architectureSignificant lociGenetic variationMultiple traitsGene expressionAssociation studiesLociTraitsGenetic knowledgeComposite phenotypeUK BiobankExpressionTENM2GNAI1GenesGeneticsVariantsPhenotype
2018
Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder
Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, Baldursson G, Belliveau R, Bybjerg-Grauholm J, Bækvad-Hansen M, Cerrato F, Chambert K, Churchhouse C, Dumont A, Eriksson N, Gandal M, Goldstein JI, Grasby KL, Grove J, Gudmundsson OO, Hansen CS, Hauberg ME, Hollegaard MV, Howrigan DP, Huang H, Maller JB, Martin AR, Martin NG, Moran J, Pallesen J, Palmer DS, Pedersen CB, Pedersen MG, Poterba T, Poulsen JB, Ripke S, Robinson EB, Satterstrom FK, Stefansson H, Stevens C, Turley P, Walters GB, Won H, Wright MJ, Andreassen O, Asherson P, Burton C, Boomsma D, Cormand B, Dalsgaard S, Franke B, Gelernter J, Geschwind D, Hakonarson H, Haavik J, Kranzler H, Kuntsi J, Langley K, Lesch K, Middeldorp C, Reif A, Rohde L, Roussos P, Schachar R, Sklar P, Sonuga-Barke E, Sullivan P, Thapar A, Tung J, Waldman I, Medland S, Stefansson K, Nordentoft M, Hougaard D, Werge T, Mors O, Mortensen P, Daly M, Faraone S, Børglum A, Neale B. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics 2018, 51: 63-75. PMID: 30478444, PMCID: PMC6481311, DOI: 10.1038/s41588-018-0269-7.Peer-Reviewed Original ResearchConceptsGenome-wide significant risk lociFunction intolerant genesGenome-wide associationSignificant risk lociGenome-wide significanceAttention-deficit/hyperactivity disorderCommon genetic variantsGenomic regionsIntolerant genesIndependent lociRegulatory marksHeritable traitRisk lociDeficit/hyperactivity disorderGenetic variantsGenetic overlapStudy-specific differencesLociHyperactivity disorderImportant new informationUnderlying biologyChildhood behavioral disordersVariantsStrong concordanceGWAS
2017
Genetic–epigenetic interactions in cis: a major focus in the post-GWAS era
Do C, Shearer A, Suzuki M, Terry MB, Gelernter J, Greally JM, Tycko B. Genetic–epigenetic interactions in cis: a major focus in the post-GWAS era. Genome Biology 2017, 18: 120. PMID: 28629478, PMCID: PMC5477265, DOI: 10.1186/s13059-017-1250-y.Peer-Reviewed Original ResearchConceptsMethylation quantitative trait lociCCCTC-binding factorEpigenome-wide association studiesGenetic-epigenetic interactionsAllele-specific DNA methylationSequence variantsPost-GWAS eraQuantitative trait lociRegulatory sequence variantsGWAS signalsTrait lociDNA methylationTranscription factorsTranscriptional pathwaysAssociation studiesNon-genetic effectsStudy eraMajor focusMethylationLociVariantsCommon diseaseSitesNeuropsychiatric disordersPathway
2015
Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence
Hancock DB, Reginsson GW, Gaddis NC, Chen X, Saccone NL, Lutz SM, Qaiser B, Sherva R, Steinberg S, Zink F, Stacey SN, Glasheen C, Chen J, Gu F, Frederiksen BN, Loukola A, Gudbjartsson DF, Brüske I, Landi MT, Bickeböller H, Madden P, Farrer L, Kaprio J, Kranzler HR, Gelernter J, Baker TB, Kraft P, Amos CI, Caporaso NE, Hokanson JE, Bierut LJ, Thorgeirsson TE, Johnson EO, Stefansson K. Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence. Translational Psychiatry 2015, 5: e651-e651. PMID: 26440539, PMCID: PMC4930126, DOI: 10.1038/tp.2015.149.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesEuropean ancestry samplesNonsense-mediated decayWide significant associationsNicotinic receptor subunit geneReceptor subunit genesImportant regulatory propertiesNicotine dependenceSubunit geneAssociation studiesChromosome 20q13Regulatory propertiesLung cancer riskNovel variantsNormal human brainSmoking-related consequencesLung cancerCancer riskFagerström TestCHRNA4Smoking behaviorSignificant associationVariantsGenomeGenesDissecting ancestry genomic background in substance dependence genome-wide association studies
Polimanti R, Yang C, Zhao H, Gelernter J. Dissecting ancestry genomic background in substance dependence genome-wide association studies. Pharmacogenomics 2015, 16: 1487-1498. PMID: 26267224, PMCID: PMC4632979, DOI: 10.2217/pgs.15.91.Peer-Reviewed Original ResearchMeSH KeywordsAlcoholismAlgorithmsAllelesBlack or African AmericanGene FrequencyGene-Environment InteractionGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyHaplotypesHumansMolecular Sequence AnnotationOpioid-Related DisordersSubstance-Related DisordersTobacco Use DisorderWhite PeopleConceptsGenome-wide association studiesGenomic backgroundFunctional allelesAssociation studiesCommon functional allelesWide association studyLocal haplotype structureGenetic lociSD traitHaplotype structureRelevant genesGenesLociInteractive partnersPopulation diversityHigh frequency differencesAllelesFrequency differenceGenomeTraitsDiversityRoleVariants
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 variationVariantsSequencingThe effects of a MAP2K5 microRNA target site SNP on risk for anxiety and depressive disorders
Jensen KP, Kranzler HR, Stein MB, Gelernter J. The effects of a MAP2K5 microRNA target site SNP on risk for anxiety and depressive disorders. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2014, 165: 175-183. PMID: 24436253, PMCID: PMC4174417, DOI: 10.1002/ajmg.b.32219.Peer-Reviewed Original ResearchConceptsGene-trait relationshipsGWAS-identified variantsRegulation of mRNAGWAS signalsComplex traitsTrait associationsTarget genesStudy signalsSNP associationsRisk genesFunctional variantsSNPsGenesAnxiety-related traitsGene SNPsTraitsMRNAMAP2K5MicroRNAsMajor psychiatric disordersVariantsSite informationMitogenRegulationPathwaySLC6A4 polymorphism, population genetics, and psychiatric traits
Gelernter J. SLC6A4 polymorphism, population genetics, and psychiatric traits. Human Genetics 2014, 133: 459-461. PMID: 24385047, PMCID: PMC3992709, DOI: 10.1007/s00439-013-1412-2.Peer-Reviewed Original Research
2013
Exploring the genetic architecture of alcohol dependence in African-Americans via analysis of a genomewide set of common variants
Yang C, Li C, Kranzler HR, Farrer LA, Zhao H, Gelernter J. Exploring the genetic architecture of alcohol dependence in African-Americans via analysis of a genomewide set of common variants. Human Genetics 2013, 133: 617-624. PMID: 24297757, PMCID: PMC3988209, DOI: 10.1007/s00439-013-1399-8.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsPhenotypic varianceGenetic architectureSubset of SNPsTop single nucleotide polymorphismsKb of genesCommon variantsAD risk genesCommon single nucleotide polymorphismsGenome partitioningGenomewide association studiesPolygenic traitChromosome 4Illumina OmniAssociation studiesRisk genesGenetic variantsGenomewide setComplex psychiatric disorderGenesFunctional partitioningMultiple variantsGenetic factorsDevelopment of ADVariantsAssociation of Gamma-Aminobutyric Acid A Receptor α2 Gene (GABRA2) with Alcohol Use Disorder
Li D, Sulovari A, Cheng C, Zhao H, Kranzler HR, Gelernter J. Association of Gamma-Aminobutyric Acid A Receptor α2 Gene (GABRA2) with Alcohol Use Disorder. Neuropsychopharmacology 2013, 39: 907-918. PMID: 24136292, PMCID: PMC3924525, DOI: 10.1038/npp.2013.291.Peer-Reviewed Original ResearchConceptsReceptor geneGABA receptor genesGABAA receptor genesCandidate gene association studiesSAGE data setsBonferroni-corrected thresholdGene association studiesSingle nucleotide polymorphismsAssociation studiesGenotype dataStudy of AddictionGamma-aminobutyric acidMammalian brainGenesComplex disorderGABRA2 single nucleotide polymorphismsSubstance dependenceMajor inhibitory neurotransmitterGeneticsInhibitory neurotransmitterVariantsGABA receptorsSignificant associationSubstance abuseMethamphetamine dependenceThe 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
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
2006
Mutation 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 malesVariationScreenDHPLC
2000
Variant detection at the δ opioid receptor (OPRD1) locus and population genetics of a novel variant affecting protein sequence
Gelernter J, Kranzler H. Variant detection at the δ opioid receptor (OPRD1) locus and population genetics of a novel variant affecting protein sequence. Human Genetics 2000, 107: 86-88. PMID: 10982041, DOI: 10.1007/s004390000340.Peer-Reviewed Original ResearchConceptsPopulation geneticsProtein sequencesPopulation genetic dataAmino acid sequenceNovel variantsΔ locusAcid sequenceGenetic dataReceptor locusExon 1LociReceptor geneOpioid receptor geneCommon variantsEuropean populationsAllele frequenciesGeneticsVariant detectionSequenceAllelesOpioid dependenceVariantsPhysiologic effectsG alleleSubstance dependence
1998
DRD2 Allele Frequencies and Linkage Disequilibria, Including the -141CIns/DelPromoter Polymorphism, in European-American, African-American, and Japanese Subjects
Gelernter J, Kranzler H, Cubells JF, Ichinose H, Nagatsu T. DRD2 Allele Frequencies and Linkage Disequilibria, Including the -141CIns/DelPromoter Polymorphism, in European-American, African-American, and Japanese Subjects. Genomics 1998, 51: 21-26. PMID: 9693029, DOI: 10.1006/geno.1998.5264.Peer-Reviewed Original ResearchConceptsLinkage disequilibriumFunctional variantsSignificant linkage disequilibriumMutational analysis studiesFirst intronKb 5Linkage disequilibriaFrequencies of haplotypesPopulation stratificationGenetic associationDrd2 promoterPhysiological basisAllele frequenciesPhysiological relationshipGenesReceptor allelesEuropean-American subjectsD2 dopamine receptor (DRD2) allelesDisequilibriumBehavioral phenotypesPhenotypeFunctional meaningEuropean originVariantsAmerican population
1993
Mutational analysis of candidate genes in psychiatric disorders
Gejman P, Gelernter J. Mutational analysis of candidate genes in psychiatric disorders. American Journal Of Medical Genetics 1993, 48: 184-191. PMID: 8135301, DOI: 10.1002/ajmg.1320480404.Peer-Reviewed Original ResearchConceptsMutational analysisDNA samplesGradient gel electrophoresis (DGGE) techniqueDNA sequencesNucleotide sequenceSequence variationCandidate genesSequence variantsNew sequence variationsChemical cleavageGel electrophoresis techniqueExistence of variationGenetic hypothesisGenesMolecular screeningMutation screeningAffected individualsSequenceElectrophoresis techniqueMutationsCleavageVariationVariants