2022
Exploring the genetic overlap between twelve psychiatric disorders
Romero C, Werme J, Jansen P, Gelernter J, Stein M, Levey D, Polimanti R, de Leeuw C, Posthuma D, Nagel M, van der Sluis S. Exploring the genetic overlap between twelve psychiatric disorders. Nature Genetics 2022, 54: 1795-1802. PMID: 36471075, DOI: 10.1038/s41588-022-01245-2.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsPleiotropic single nucleotide polymorphismsPositive genetic correlationStringent P-value thresholdGenetic architectureGenomic regionsGenetic covarianceBiological processesBiological pathwaysMolecular characterizationObserved phenotypicGenetic correlationsGenetic overlapBiological characterizationBiological mechanismsP-value thresholdOnly annotationGenesPleiotropicPairwise comparisonsPhenotypicPathwayAnnotationPolymorphismCharacterization
2021
Drinking and smoking polygenic risk is associated with childhood and early-adulthood psychiatric and behavioral traits independently of substance use and psychiatric genetic risk
De Angelis F, Wendt FR, Pathak GA, Tylee DS, Goswami A, Gelernter J, Polimanti R. Drinking and smoking polygenic risk is associated with childhood and early-adulthood psychiatric and behavioral traits independently of substance use and psychiatric genetic risk. Translational Psychiatry 2021, 11: 586. PMID: 34775470, PMCID: PMC8590689, DOI: 10.1038/s41398-021-01713-z.Peer-Reviewed Original ResearchConceptsSubstance useYoung adultsBehavioral traitsPhiladelphia Neurodevelopmental CohortRemoval of participantsAnxiety-related traitsRisk-taking behaviorVerbal reasoningCognitive performancePolygenic risk scoresSocial competenciesNeurobiological processesNeurodevelopmental CohortPsychiatric genetic riskDrinking behaviorParent educationPRS associationsPolygenic riskPsychopathologyGenetic overlapPsychotic symptomsAdverse health outcomesHazardous behaviorEducational attainmentTobacco smokingInvestigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder
Johnson EC, Kapoor M, Hatoum AS, Zhou H, Polimanti R, Wendt FR, Walters RK, Lai D, Kember RL, Hartz S, Meyers JL, Peterson RE, Ripke S, Bigdeli TB, Fanous AH, Pato CN, Pato MT, Goate AM, Kranzler HR, O'Donovan MC, Walters JTR, Gelernter J, Edenberg HJ, Agrawal A. Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder. Psychological Medicine 2021, 53: 1196-1204. PMID: 34231451, PMCID: PMC8738774, DOI: 10.1017/s003329172100266x.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significant single nucleotide polymorphismsLarge-scale genome-wide association studiesSignificant single nucleotide polymorphismsIndependent genome-wide significant single nucleotide polymorphismsSignificant genetic correlationsGenomic regionsSingle nucleotide polymorphismsGene expressionGenetic covariancePleiotropic associationsAssociation studiesGenetic correlationsGenetic variantsNucleotide polymorphismsGenetic overlapDisorder-specific effectsAlcohol use disorderGenetic influencesGenesUse disordersPsychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder
Mundy J, Hübel C, Gelernter J, Levey D, Murray RM, Skelton M, Stein MB, Maihofer A, Nievergelt C, Baker D, Risborough V, Calabrese J, Galea S, Stein D, Koen N, Dalvie S, Aiello A, Roberts A, Koenen K, Solovieff N, Kranzler H, Zhao H, Gelernter J, Farrer L, Johnson E, Rice J, Bierut L, Saccone N, McFarlane A, Forbes D, Silove D, O'Donnell M, Bryant R, van Hooff M, Sponheim S, Disner S, Pietrzak R, Chen C, Smoller J, Stein M, Ursano R, Kessler R, Junglen A, Delahanty D, Amstadter A, Sheerin C, Ruggiero K, McLaughlin K, Peverill M, Caldas-de-Almeida J, Austin S, Gelaye B, Williams M, Sanchez S, Franz C, Panizzon M, Lyons M, Kremen W, Andreassen O, Dale A, Rutten B, Vinkers C, Schijven D, Geuze E, Vermetten E, Luykx J, Boks M, Ashley-Koch A, Beckham J, Garrett M, Hauser M, Dennis M, Kimbrel N, Qin X, Karstoft K, Andersen S, Borglum A, Hougaard D, Bybjerg-Grauholm J, Duncan L, Bµkvad-Hansen M, Nordentoft M, Mors O, Mortensen P, Werge T, Thompson W, Wang Y, Heath A, Nelson E, Martin N, Gordon S, Wolf E, Logue M, Miller M, McGlinchey R, Milberg W, Erbes C, Polusny M, Arbisi P, Peterson A, Williamson D, Young K, Maurer D, Rothbaum A, Zoellner L, Mavissakalian M, Feeny N, Roy-Byrne P, Rothbaum B, Maples-Keller J, Khan A, Wolff J, Lebois L, Teicher M, Kaufman M, Winternitz S, Bolger E, Seligowski A, Orcutt H, Evans A, Lugonja B, Lewis C, Jones I, Bisson J, McLean S, Linnstaedt S, Peters E, Rung A, Trapido E, Brashear M, Lori A, Smith A, Bradley B, Gillespie C, Guffanti G, Ressler K, Almli L, Jovanovic T, Bustamante A, Uddin M, van den Heuvel L, Seedat S, Hemmings S, Uka A, Kulenovic A, Wolf C, Babic D, Avdibegovic E, Deckert J, Domschke K, Jakovljevic M, Marmar C, Flory J, Jett M, Yehuda R, Hammamieh R, King A, Liberzon I, Seng J, Morris C, Mehta D, Voisey J, Lawford B, Young R, McLeay S, Daskalakis N, Norman S, Wang Z, Breen G, Coleman J, Klengel T, Torres K, Choi K, Levey D, Polimanti R, Atkinson E, Martin A, Neale B, Daly M, Ripke S, Ratanatharathorn A, Provost A, Haas M, Stevens J, Morey R, Harnal S, Mortensen P, Seedat S, Sumner J, Vassos E, Breen G, Coleman J. Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder. Psychological Medicine 2021, 52: 3975-3984. PMID: 34085609, PMCID: PMC8962503, DOI: 10.1017/s0033291721000830.Peer-Reviewed Original ResearchRecurrent major depressive disorderMajor depressive disorderPosttraumatic stress disorderSingle-episode major depressive disorderDepressive disorderTrauma exposureStress disorderPsychological trauma exposureLifetime major depressive disorderTrauma sensitivityGenetic loadingUK Biobank participantsKey risk factorsMental health consequencesRisk factorsMillion Veteran ProgramPolygenic risk scoresRisk scoreGenetic overlapHealth consequencesBiobank participantsTraumaDisordersVeteran ProgramPsychiatric Genomics Consortium
2020
Multivariate genome-wide analysis of education, socioeconomic status and brain phenome
Wendt FR, Pathak GA, Lencz T, Krystal JH, Gelernter J, Polimanti R. Multivariate genome-wide analysis of education, socioeconomic status and brain phenome. Nature Human Behaviour 2020, 5: 482-496. PMID: 33349686, PMCID: PMC8068566, DOI: 10.1038/s41562-020-00980-y.Peer-Reviewed Original ResearchConceptsPsychosocial factorsSocioeconomic statusPsychiatric disordersBipolar disorderGenetic riskNeuronal cell typesMajor depressionTourette syndromeBrain morphologyDisordersImaging phenotypesCell typesRisky behaviorsPsychopathologyGenetic overlapRiskGenetic discoveriesPsychiatric traitsStatusSyndromeA large-scale genome-wide association study meta-analysis of cannabis use disorder
Johnson EC, Demontis D, Thorgeirsson TE, Walters RK, Polimanti R, Hatoum AS, Sanchez-Roige S, Paul SE, Wendt FR, Clarke TK, Lai D, Reginsson GW, Zhou H, He J, Baranger DAA, Gudbjartsson DF, Wedow R, Adkins DE, Adkins AE, Alexander J, Bacanu SA, Bigdeli TB, Boden J, Brown SA, Bucholz KK, Bybjerg-Grauholm J, Corley RP, Degenhardt L, Dick DM, Domingue BW, Fox L, Goate AM, Gordon SD, Hack LM, Hancock DB, Hartz SM, Hickie IB, Hougaard DM, Krauter K, Lind PA, McClintick JN, McQueen MB, Meyers JL, Montgomery GW, Mors O, Mortensen PB, Nordentoft M, Pearson JF, Peterson RE, Reynolds MD, Rice JP, Runarsdottir V, Saccone NL, Sherva R, Silberg JL, Tarter RE, Tyrfingsson T, Wall TL, Webb BT, Werge T, Wetherill L, Wright MJ, Zellers S, Adams MJ, Bierut LJ, Boardman JD, Copeland WE, Farrer LA, Foroud TM, Gillespie NA, Grucza RA, Harris KM, Heath AC, Hesselbrock V, Hewitt JK, Hopfer CJ, Horwood J, Iacono WG, Johnson EO, Kendler KS, Kennedy MA, Kranzler HR, Madden PAF, Maes HH, Maher BS, Martin NG, McGue M, McIntosh AM, Medland SE, Nelson EC, Porjesz B, Riley BP, Stallings MC, Vanyukov MM, Vrieze S, Workgroup P, Walters R, Polimanti R, Johnson E, McClintick J, Hatoum A, He J, Wendt F, Zhou H, Adams M, Adkins A, Aliev F, Bacanu S, Batzler A, Bertelsen S, Biernacka J, Bigdeli T, Chen L, Clarke T, Chou Y, Degenhardt F, Docherty A, Edwards A, Fontanillas P, Foo J, Fox L, Frank J, Giegling I, Gordon S, Hack L, Hartmann A, Hartz S, Heilmann-Heimbach S, Herms S, Hodgkinson C, Hoffman P, Hottenga J, Kennedy M, Alanne-Kinnunen M, Konte B, Lahti J, Lahti-Pulkkinen M, Lai D, Ligthart L, Loukola A, Maher B, Mbarek H, McIntosh A, McQueen M, Meyers J, Milaneschi Y, Palviainen T, Pearson J, Peterson R, Ripatti S, Ryu E, Saccone N, Salvatore J, Sanchez-Roige S, Schwandt M, Sherva R, Streit F, Strohmaier J, Thomas N, Wang J, Webb B, Wedow R, Wetherill L, Wills A, Boardman J, Chen D, Choi D, Copeland W, Culverhouse R, Dahmen N, Degenhardt L, Domingue B, Elson S, Frye M, Gäbel W, Hayward C, Ising M, Keyes M, Kiefer F, Kramer J, Kuperman S, Lucae S, Lynskey M, Maier W, Mann K, Männistö S, Müller-Myhsok B, Murray A, Nurnberger J, Palotie A, Preuss U, Räikkönen K, Reynolds M, Ridinger M, Scherbaum N, Schuckit M, Soyka M, Treutlein J, Witt S, Wodarz N, Zill P, Adkins D, Boden J, Boomsma D, Bierut L, Brown S, Bucholz K, Cichon S, Costello E, de Wit H, Diazgranados N, Dick D, Eriksson J, Farrer L, Foroud T, Gillespie N, Goate A, Goldman D, Grucza R, Hancock D, Harris K, Heath A, Hesselbrock V, Hewitt J, Hopfer C, Horwood J, Iacono W, Johnson E, Kaprio J, Karpyak V, Kendler K, Kranzler H, Krauter K, Lichtenstein P, Lind P, McGue M, MacKillop J, Madden P, Maes H, Magnusson P, Martin N, Medland S, Montgomery G, Nelson E, Nöthen M, Palmer A, Pederson N, Penninx B, Porjesz B, Rice J, Rietschel M, Riley B, Rose R, Rujescu D, Shen P, Silberg J, Stallings M, Tarter R, Vanyukov M, Vrieze S, Wall T, Whitfield J, Zhao H, Neale B, Gelernter J, Edenberg H, Agrawal A, Davis L, Bogdan R, Gelernter J, Edenberg H, Stefansson K, Børglum A, Agrawal A. A large-scale genome-wide association study meta-analysis of cannabis use disorder. The Lancet Psychiatry 2020, 7: 1032-1045. PMID: 33096046, PMCID: PMC7674631, DOI: 10.1016/s2215-0366(20)30339-4.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesGenome-wide significant lociLarge-scale genome-wide association studiesGenetic correlationsChromosome 7 locusTraits of interestLarge genome-wide association studiesLinkage disequilibrium score regressionChromosome 8 locusDifferent genetic underpinningsDifferent genetic correlationsWellcome Trust Case Control ConsortiumDisequilibrium score regressionNovel genetic variantsStrong genetic componentSignificant lociGenetic lociGenetic underpinningsGenetic componentLociScore regressionGenetic variantsGenetic overlapIntegrative sequencing
2019
Genetic associations with suicide attempt severity and genetic overlap with major depression
Levey DF, Polimanti R, Cheng Z, Zhou H, Nuñez YZ, Jain S, He F, Sun X, Ursano RJ, Kessler RC, Smoller JW, Stein MB, Kranzler HR, Gelernter J. Genetic associations with suicide attempt severity and genetic overlap with major depression. Translational Psychiatry 2019, 9: 22. PMID: 30655502, PMCID: PMC6336846, DOI: 10.1038/s41398-018-0340-2.Peer-Reviewed Original ResearchConceptsGWS associationsGenome-wide significant signalsCircadian clock regulationWide association studyGenetic overlapCatabolism of tyrosineClock regulationFirst GWASSignificant genetic overlapDiscovery GWASChromosome 12Large GWASMolecular mechanismsAssociation studiesChromosome 15Chromosome 18Genetic influencesDiscovery sampleGenetic associationSuicide attempt severityReplication analysisGWASAnaerobic energy productionGenetic risk factorsPolygenic risk scoresA Putative Causal Relationship Between Genetically Determined Female Body Shape And Post-Traumatic Stress Disorder
Polimanti R, Amstadter A, Liberzon I, Nievergelt C, Workgroup P, Stein M, Koenen K, Gelernter J. A Putative Causal Relationship Between Genetically Determined Female Body Shape And Post-Traumatic Stress Disorder. European Neuropsychopharmacology 2019, 29: s751-s752. DOI: 10.1016/j.euroneuro.2017.06.094.Peer-Reviewed Original ResearchGenome-wide association studiesLarge genome-wide association studiesPutative causal relationshipAnthropometric traitsBody shapeEvolutionary mechanismsTop associationsAssociation studiesReproductive behaviorGenetic correlationsPleiotropic effectsGenetic overlapFemale body shapePolygenic score approachTraitsMendelian randomization analysisSummary statisticsRandomization analysisHuman sexual behaviorMechanism
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 concordanceGWASGWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability
Pasman JA, Verweij KJH, Gerring Z, Stringer S, Sanchez-Roige S, Treur JL, Abdellaoui A, Nivard MG, Baselmans BML, Ong JS, Ip HF, van der Zee MD, Bartels M, Day FR, Fontanillas P, Elson SL, the 23andMe Research Team, de Wit H, Davis LK, MacKillop J, The Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Derringer JL, Branje SJT, Hartman CA, Heath AC, van Lier PAC, Madden PAF, Mägi R, Meeus W, Montgomery GW, Oldehinkel AJ, Pausova Z, Ramos-Quiroga JA, Paus T, Ribases M, Kaprio J, Boks MPM, Bell JT, Spector TD, Gelernter J, Boomsma DI, Martin NG, MacGregor S, Perry JRB, Palmer AA, Posthuma D, Munafò MR, Gillespie NA, Derks EM, Vink JM. GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability. Nature Neuroscience 2018, 21: 1161-1170. PMID: 30150663, PMCID: PMC6386176, DOI: 10.1038/s41593-018-0206-1.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overCell Adhesion MoleculesDatabases, GeneticFemaleGene Expression RegulationGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMaleMarijuana AbuseMendelian Randomization AnalysisMental HealthMiddle AgedPolymorphism, Single NucleotideRisk-TakingSchizophreniaYoung AdultConceptsGenome-wide association studiesNew risk lociLarge genome-wide association studiesGene-based testsIndependent single nucleotide polymorphismsDifferent expression levelsSignificant genetic correlationsHealth-related traitsSingle nucleotide polymorphismsEtiology of cannabisHeritable traitRisk lociSignificant genesAssociation studiesGenetic correlationsPsychiatric traitsGenetic variantsNucleotide polymorphismsGenetic overlapExpression levelsTraitsGenesNew insightsSchizophrenia riskMendelian randomization analysis
2017
A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder
Polimanti R, Amstadter AB, Stein MB, Almli LM, Baker DG, Bierut LJ, Bradley B, Farrer LA, Johnson EO, King A, Kranzler HR, Maihofer AX, Rice JP, Roberts AL, Saccone NL, Zhao H, Liberzon I, Ressler KJ, Nievergelt CM, Koenen KC, Gelernter J, for The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup. A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder. Genome Medicine 2017, 9: 99. PMID: 29178946, PMCID: PMC5702961, DOI: 10.1186/s13073-017-0491-4.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesLarge genome-wide association studiesPutative causal relationshipAnthropometric traitsBody shapeEvolutionary mechanismsTop associationsAssociation studiesReproductive behaviorGenetic correlationsPleiotropic effectsGenetic overlapFemale body shapePolygenic score approachTraitsMendelian randomization analysisSummary statisticsRandomization analysisHuman sexual behaviorMechanism
2015
Polygenic risk for alcohol dependence associates with alcohol consumption, cognitive function and social deprivation in a population‐based cohort
Clarke T, Smith AH, Gelernter J, Kranzler HR, Farrer LA, Hall LS, Fernandez‐Pujals A, MacIntyre DJ, Smith BH, Hocking LJ, Padmanabhan S, Hayward C, Thomson PA, Porteous DJ, Deary IJ, McIntosh AM. Polygenic risk for alcohol dependence associates with alcohol consumption, cognitive function and social deprivation in a population‐based cohort. Addiction Biology 2015, 21: 469-480. PMID: 25865819, PMCID: PMC4600406, DOI: 10.1111/adb.12245.Peer-Reviewed Original ResearchConceptsCognitive abilitiesCognitive functionAlcohol dependenceCognitive impairmentPrevalence of problemsPolygenic risk scoresOnset of dependenceCognitive dysfunctionFamily Health StudyScottish Family Health StudySocial deprivationSignificant negative associationHeavy drinkingGenetic overlapNegative associationImpairmentPhenotypic associationsAlcohol consumptionCognitionDeprivationFuture workPresent studyAbilityAssociationDrinking
2014
Genetic risk prediction and neurobiological understanding of alcoholism
Levey DF, Le-Niculescu H, Frank J, Ayalew M, Jain N, Kirlin B, Learman R, Winiger E, Rodd Z, Shekhar A, Schork N, Kiefe F, Wodarz N, Müller-Myhsok B, Dahmen N, Nöthen M, Sherva R, Farrer L, Smith A, Kranzler H, Rietschel M, Gelernter J, Niculescu A. Genetic risk prediction and neurobiological understanding of alcoholism. Translational Psychiatry 2014, 4: e391-e391. PMID: 24844177, PMCID: PMC4035721, DOI: 10.1038/tp.2014.29.Peer-Reviewed Original ResearchConceptsTop candidate genesCandidate genesGenetic risk predictionGenome-wide association study dataFunctional genomics approachConvergent functional genomics approachAssociation study dataGene expression dataInitial discovery stepGenomic approachesKey genesSignal transductionSignificant genetic overlapTop genesRelevant genesBiological pathwaysExpression dataTop findingsGenesStrict Bonferroni correctionGenetic overlapProtein knockout miceSmall panelFatty acidsKnockout mice