2023
Depression pathophysiology, risk prediction of recurrence and comorbid psychiatric disorders using genome-wide analyses
Als T, Kurki M, Grove J, Voloudakis G, Therrien K, Tasanko E, Nielsen T, Naamanka J, Veerapen K, Levey D, Bendl J, Bybjerg-Grauholm J, Zeng B, Demontis D, Rosengren A, Athanasiadis G, Bækved-Hansen M, Qvist P, Bragi Walters G, Thorgeirsson T, Stefánsson H, Musliner K, Rajagopal V, Farajzadeh L, Thirstrup J, Vilhjálmsson B, McGrath J, Mattheisen M, Meier S, Agerbo E, Stefánsson K, Nordentoft M, Werge T, Hougaard D, Mortensen P, Stein M, Gelernter J, Hovatta I, Roussos P, Daly M, Mors O, Palotie A, Børglum A. Depression pathophysiology, risk prediction of recurrence and comorbid psychiatric disorders using genome-wide analyses. Nature Medicine 2023, 29: 1832-1844. PMID: 37464041, PMCID: PMC10839245, DOI: 10.1038/s41591-023-02352-1.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphism heritabilityGenome-wide analysisLikely causal genesFunctional genomics dataRisk variantsWide association studyPolygenic burdenPsychiatric disordersCausal genesPolygenic architectureGenomic dataRisk lociAssociation studiesSubgroups of depressionCause of disabilityDepression genetic riskCommon psychiatric disordersPrecision medicine approachCases of depressionOligodendrocyte lineageGenesLociConsiderable sex differencesGABAergic neuronsPsychiatric comorbidity
2021
Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
Mullins N, Forstner AJ, O’Connell K, Coombes B, Coleman JRI, Qiao Z, Als TD, Bigdeli TB, Børte S, Bryois J, Charney AW, Drange OK, Gandal MJ, Hagenaars SP, Ikeda M, Kamitaki N, Kim M, Krebs K, Panagiotaropoulou G, Schilder BM, Sloofman LG, Steinberg S, Trubetskoy V, Winsvold BS, Won HH, Abramova L, Adorjan K, Agerbo E, Al Eissa M, Albani D, Alliey-Rodriguez N, Anjorin A, Antilla V, Antoniou A, Awasthi S, Baek JH, Bækvad-Hansen M, Bass N, Bauer M, Beins EC, Bergen SE, Birner A, Bøcker Pedersen C, Bøen E, Boks MP, Bosch R, Brum M, Brumpton BM, Brunkhorst-Kanaan N, Budde M, Bybjerg-Grauholm J, Byerley W, Cairns M, Casas M, Cervantes P, Clarke TK, Cruceanu C, Cuellar-Barboza A, Cunningham J, Curtis D, Czerski PM, Dale AM, Dalkner N, David FS, Degenhardt F, Djurovic S, Dobbyn AL, Douzenis A, Elvsåshagen T, Escott-Price V, Ferrier IN, Fiorentino A, Foroud TM, Forty L, Frank J, Frei O, Freimer NB, Frisén L, Gade K, Garnham J, Gelernter J, Giørtz Pedersen M, Gizer IR, Gordon SD, Gordon-Smith K, Greenwood TA, Grove J, Guzman-Parra J, Ha K, Haraldsson M, Hautzinger M, Heilbronner U, Hellgren D, Herms S, Hoffmann P, Holmans PA, Huckins L, Jamain S, Johnson JS, Kalman JL, Kamatani Y, Kennedy JL, Kittel-Schneider S, Knowles JA, Kogevinas M, Koromina M, Kranz TM, Kranzler HR, Kubo M, Kupka R, Kushner SA, Lavebratt C, Lawrence J, Leber M, Lee HJ, Lee PH, Levy SE, Lewis C, Liao C, Lucae S, Lundberg M, MacIntyre DJ, Magnusson SH, Maier W, Maihofer A, Malaspina D, Maratou E, Martinsson L, Mattheisen M, McCarroll SA, McGregor NW, McGuffin P, McKay JD, Medeiros H, Medland SE, Millischer V, Montgomery GW, Moran JL, Morris DW, Mühleisen TW, O’Brien N, O’Donovan C, Olde Loohuis LM, Oruc L, Papiol S, Pardiñas AF, Perry A, Pfennig A, Porichi E, Potash JB, Quested D, Raj T, Rapaport MH, DePaulo JR, Regeer EJ, Rice JP, Rivas F, Rivera M, Roth J, Roussos P, Ruderfer DM, Sánchez-Mora C, Schulte EC, Senner F, Sharp S, Shilling PD, Sigurdsson E, Sirignano L, Slaney C, Smeland OB, Smith DJ, Sobell JL, Søholm Hansen C, Soler Artigas M, Spijker AT, Stein DJ, Strauss JS, Świątkowska B, Terao C, Thorgeirsson TE, Toma C, Tooney P, Tsermpini EE, Vawter MP, Vedder H, Walters JTR, Witt SH, Xi S, Xu W, Yang JMK, Young AH, Young H, Zandi PP, Zhou H, Zillich L, Adolfsson R, Agartz I, Alda M, Alfredsson L, Babadjanova G, Backlund L, Baune B, Bellivier F, Bengesser S, Berrettini W, Blackwood D, Boehnke M, Børglum A, Breen G, Carr V, Catts S, Corvin A, Craddock N, Dannlowski U, Dikeos D, Esko T, Etain B, Ferentinos P, Frye M, Fullerton J, Gawlik M, Gershon E, Goes F, Green M, Grigoroiu-Serbanescu M, Hauser J, Henskens F, Hillert J, Hong K, Hougaard D, Hultman C, Hveem K, Iwata N, Jablensky A, Jones I, Jones L, Kahn R, Kelsoe J, Kirov G, Landén M, Leboyer M, Lewis C, Li Q, Lissowska J, Lochner C, Loughland C, Martin N, Mathews C, Mayoral F, McElroy S, McIntosh A, McMahon F, Melle I, Michie P, Milani L, Mitchell P, Morken G, Mors O, Mortensen P, Mowry B, Müller-Myhsok B, Myers R, Neale B, Nievergelt C, Nordentoft M, Nöthen M, O’Donovan M, Oedegaard K, Olsson T, Owen M, Paciga S, Pantelis C, Pato C, Pato M, Patrinos G, Perlis R, Posthuma D, Ramos-Quiroga J, Reif A, Reininghaus E, Ribasés M, Rietschel M, Ripke S, Rouleau G, Saito T, Schall U, Schalling M, Schofield P, Schulze T, Scott L, Scott R, Serretti A, Shannon Weickert C, Smoller J, Stefansson H, Stefansson K, Stordal E, Streit F, Sullivan P, Turecki G, Vaaler A, Vieta E, Vincent J, Waldman I, Weickert T, Werge T, Wray N, Zwart J, Biernacka J, Nurnberger J, Cichon S, Edenberg H, Stahl E, McQuillin A, Di Florio A, Ophoff R, Andreassen O. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nature Genetics 2021, 53: 817-829. PMID: 34002096, PMCID: PMC8192451, DOI: 10.1038/s41588-021-00857-4.Peer-Reviewed Original ResearchConceptsAssociation studiesQuantitative trait loci dataExpression quantitative trait loci (eQTL) dataGenome-wide association studiesBipolar disorder casesBrain-expressed genesWide association studyHeritable mental illnessSynaptic signaling pathwaysGenomic lociTargets of antipsychoticsLoci dataImperfect genetic correlationGene expressionSignaling pathwaysFunctional followGenesGenetic correlationsDruggable targetsSignal enrichmentEuropean ancestryLociBipolar disorder risk allelesNew insightsTherapeutic leads
2018
Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls
Pettersson E, Lichtenstein P, Larsson H, Song J, Agrawal A, Børglum A, Bulik C, Daly M, Davis L, Demontis D, Edenberg H, Grove J, Gelernter J, Neale B, Pardiñas A, Stahl E, Walters J, Walters R, Sullivan P, Posthuma D, Polderman T. Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls. Psychological Medicine 2018, 49: 1166-1173. PMID: 30221610, PMCID: PMC6421104, DOI: 10.1017/s0033291718002039.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismAnorexia NervosaAttention Deficit Disorder with HyperactivityAutism Spectrum DisorderBipolar DisorderCase-Control StudiesCohort StudiesDepressive Disorder, MajorFamilyFemaleGene-Environment InteractionGenotypeHumansMaleMental DisordersObsessive-Compulsive DisorderQuantitative Trait, HeritableSchizophreniaSchizophrenic PsychologySiblingsSweden
2017
Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers
Polimanti R, Kaufman J, Zhao H, Kranzler HR, Ursano RJ, Kessler RC, Stein MB, Gelernter J. Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers. Acta Psychiatrica Scandinavica 2017, 137: 148-156. PMID: 29230810, PMCID: PMC6110087, DOI: 10.1111/acps.12843.Peer-Reviewed Original ResearchConceptsBD polygenic risk scorePolygenic risk scoresAlcohol misuseBipolar disorderTrauma exposurePsychiatric disordersGenetic riskMajor depressive disorderNicotine dependence symptomsSubstance use disordersSchizophrenia polygenic risk scoresVoltage-gated calcium channel activityCalcium channel activityUS Army soldiersBeta2-adrenergic receptorDepressive disorderRisk scoreUse disordersAdrenergic receptorsMental disordersSubstance abuseDisordersDependence symptomsChannel activityExposureLargest 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 evidenceWidespread 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
Cross-Phenotype Polygenic Risk Score Analysis of Persistent Post-Concussive Symptoms in U.S. Army Soldiers with Deployment-Acquired Traumatic Brain Injury
Polimanti R, Chen CY, Ursano RJ, Heeringa SG, Jain S, Kessler RC, Nock MK, Smoller JW, Sun X, Gelernter J, Stein MB. Cross-Phenotype Polygenic Risk Score Analysis of Persistent Post-Concussive Symptoms in U.S. Army Soldiers with Deployment-Acquired Traumatic Brain Injury. Journal Of Neurotrauma 2016, 34: 781-789. PMID: 27439997, PMCID: PMC5314978, DOI: 10.1089/neu.2016.4550.Peer-Reviewed Original ResearchEffects of ANK3 variation on gray and white matter in bipolar disorder
Lippard ETC, Jensen KP, Wang F, Johnston JAY, Spencer L, Pittman B, Gelernter J, Blumberg HP. Effects of ANK3 variation on gray and white matter in bipolar disorder. Molecular Psychiatry 2016, 22: 1345-1351. PMID: 27240527, PMCID: PMC5133179, DOI: 10.1038/mp.2016.76.Peer-Reviewed Original Research
2008
Role of Variation in the Serotonin Transporter Protein Gene (SLC6A4) in Trait Disturbances in the Ventral Anterior Cingulate in Bipolar Disorder
Shah MP, Wang F, Kalmar JH, Chepenik LG, Tie K, Pittman B, Jones MM, Constable RT, Gelernter J, Blumberg HP. Role of Variation in the Serotonin Transporter Protein Gene (SLC6A4) in Trait Disturbances in the Ventral Anterior Cingulate in Bipolar Disorder. Neuropsychopharmacology 2008, 34: 1301-1310. PMID: 19037205, PMCID: PMC2826628, DOI: 10.1038/npp.2008.204.Peer-Reviewed Original ResearchConceptsVentral anterior cingulate cortexBipolar disorderFeatures of BDS carriersAnterior cingulate cortexVentral anterior cingulateEvent-related functional magnetic resonanceFunctional magnetic resonanceTransporter promoter polymorphismSerotonergic systemBD subgroupsHealthy comparison participantsBD groupVACC activationHC groupPromoter polymorphismFuture treatmentHealthy individualsAnterior cingulateCingulate cortexNeural systemsFunctional connectivityDysfunctionSerotonin transporter protein geneAmygdala activationEffects of the Brain-Derived Neurotrophic Growth Factor Val66Met Variation on Hippocampus Morphology in Bipolar Disorder
Chepenik LG, Fredericks C, Papademetris X, Spencer L, Lacadie C, Wang F, Pittman B, Duncan JS, Staib LH, Duman RS, Gelernter J, Blumberg HP. Effects of the Brain-Derived Neurotrophic Growth Factor Val66Met Variation on Hippocampus Morphology in Bipolar Disorder. Neuropsychopharmacology 2008, 34: 944-951. PMID: 18704093, PMCID: PMC2837582, DOI: 10.1038/npp.2008.107.Peer-Reviewed Original ResearchConceptsSmaller hippocampus volumesHippocampus volumeBipolar disorderBDNF genotypeBD diagnosisMood disorder pathophysiologyBDNF Val66Met polymorphismHigh-resolution magnetic resonanceHealthy comparison subjectsVal/Val homozygotesEffect of diagnosisLinear mixed model analysisVal66Met polymorphismGrowth factor proteinBD subgroupsDisorder pathophysiologyHC subjectsHippocampal developmentComparison subjectsMixed model analysisHippocampus structureBDNFHippocampus morphologyAnterior hippocampusVal homozygotes
1995
Genetics of bipolar affective disorder: time for another reinvention?
Gelernter J. Genetics of bipolar affective disorder: time for another reinvention? American Journal Of Human Genetics 1995, 56: 1262-6. PMID: 7762549, PMCID: PMC1801084.Peer-Reviewed Original Research
1990
Manic depressive illness not linked to factor IX region in an independent series of pedigrees
Gejman P, Detera-Wadleigh S, Martinez M, Berrettini W, Goldin L, Gelernter J, Hsieh W, Gershon E. Manic depressive illness not linked to factor IX region in an independent series of pedigrees. Genomics 1990, 8: 648-655. PMID: 1980485, DOI: 10.1016/0888-7543(90)90251-o.Peer-Reviewed Original ResearchX-Chromosome Markers and Manic-Depressive Illness: Rejection of Linkage to Xq28 in Nine Bipolar Pedigrees
Berrettini WH, Goldin LR, Gelernter J, Gejman PV, Gershon ES, Detera-Wadleigh S. X-Chromosome Markers and Manic-Depressive Illness: Rejection of Linkage to Xq28 in Nine Bipolar Pedigrees. JAMA Psychiatry 1990, 47: 366-373. PMID: 2322087, DOI: 10.1001/archpsyc.1990.01810160066010.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 differencesPatientsCallosalGenuTemporal lobe measurement in primary affective disorder by magnetic resonance imaging
Hauser P, Altshuler LL, Berrettini W, Dauphinais ID, Gelernter J, Post RM. Temporal lobe measurement in primary affective disorder by magnetic resonance imaging. Journal Of Neuropsychiatry 1989, 1: 128-134. PMID: 2521053, DOI: 10.1176/jnp.1.2.128.Peer-Reviewed Original ResearchConceptsPrimary affective disorderTemporal lobeAffective disordersCerebral areasSpecific temporal lobe structuresTemporal lobe structuresMagnetic resonance imagingNormal controlsNormal subjectsInterpeduncular cisternBrain scansCoronal slicesResonance imagingPatientsLobe structuresDisordersLobeSame hemisphereRelative decreaseMagnetic resonanceSubjects