Featured Publications
Understanding the comorbidity between posttraumatic stress severity and coronary artery disease using genome-wide information and electronic health records
Polimanti R, Wendt FR, Pathak GA, Tylee DS, Tcheandjieu C, Hilliard AT, Levey DF, Adhikari K, Gaziano JM, O’Donnell C, Assimes TL, Stein MB, Gelernter J. Understanding the comorbidity between posttraumatic stress severity and coronary artery disease using genome-wide information and electronic health records. Molecular Psychiatry 2022, 27: 3961-3969. PMID: 35986173, PMCID: PMC10986859, DOI: 10.1038/s41380-022-01735-z.Peer-Reviewed Original ResearchConceptsCoronary artery diseasePosttraumatic stress disorderElectronic health recordsMillion Veteran ProgramArtery diseaseTotal scoreCAD diagnosisPlatelet amyloid precursor proteinHealth recordsPosttraumatic stress severityAmyloid precursor proteinEarly CAD diagnosisUK BiobankBidirectional relationshipTwo-sample Mendelian randomization (MR) analysisMendelian randomization analysisCAD riskHigh morbidityPTSD symptom severityCARDIoGRAMplusC4D consortiumPleiotropic mechanismsSymptom severityLongitudinal changesDiscordant effectsStress disorder
2024
Polygenic risk for suicide attempt is associated with lifetime suicide attempt in US soldiers independent of parental risk
Stein M, Jain S, Papini S, Campbell-Sills L, Choi K, Martis B, Sun X, He F, Ware E, Naifeh J, Aliaga P, Ge T, Consortium F, Workgroup F, Program F, Consortium F, Smoller J, Gelernter J, Kessler R, Ursano R. Polygenic risk for suicide attempt is associated with lifetime suicide attempt in US soldiers independent of parental risk. Journal Of Affective Disorders 2024, 351: 671-682. PMID: 38309480, PMCID: PMC11259154, DOI: 10.1016/j.jad.2024.01.254.Peer-Reviewed Original ResearchConceptsHistory of Major Depressive DisorderMajor depressive disorderNon-suicidal self-injuryLifetime non-suicidal self-injuryHistory of SAAssociated with lifetime SAParental historyMultivariate modelLifetime SASuicide attemptsParental major depressive disorderAssociated with non-suicidal self-injuryAssociated with lifetime suicide attemptsLifetime suicide attemptsClinical decision-makingDepressive disorderGWA studiesPolygenic risk scoresRisk scoreCohortEuropean ancestrySelf-injuryParental SAGenetic liabilityCombined analysis
2023
Genome-wide association study of antisocial personality disorder diagnostic criteria provides evidence for shared risk factors across disorders
Li W, Zhou H, Thygesen J, Heydtmann M, Smith I, Degenhardt F, Nöthen M, Morgan M, Kranzler H, Gelernter J, Bass N, McQuillin A. Genome-wide association study of antisocial personality disorder diagnostic criteria provides evidence for shared risk factors across disorders. Psychiatric Genetics 2023, 33: 233-242. PMID: 37756443, PMCID: PMC10635348, DOI: 10.1097/ypg.0000000000000352.Peer-Reviewed Original ResearchMeSH KeywordsAntisocial Personality DisorderAnxiety DisordersGenome-Wide Association StudyHumansRisk FactorsConceptsAntisocial personality disorderAttention deficit hyperactivity disorderSubstance use disordersPosttraumatic stress disorderGenome-wide association studiesDeficit hyperactivity disorderDisorder diagnostic criteriaRisk factorsFrontal cortexDiagnostic criteriaUse disordersRisk score analysisAnterior cingulateAlcohol-dependent participantsPsychiatric conditionsSignificant associationBrain regionsPersonality disorder diagnostic criteriaStress disorderAnxiety disordersASPD criteriaHyperactivity disorderPolygenic risk score analysisPersonality disorderScore analysisDoes polygenic risk for substance‐related traits predict ages of onset and progression of symptoms?
Kranzler H, Feinn R, Xu H, Ho B, Saini D, Nicastro O, Jacoby A, Toikumo S, Gelernter J, Hartwell E, Kember R. Does polygenic risk for substance‐related traits predict ages of onset and progression of symptoms? Addiction 2023, 118: 1675-1686. PMID: 37069489, PMCID: PMC10525011, DOI: 10.1111/add.16210.Peer-Reviewed Original ResearchConceptsOpioid use disorderSubstance use disordersProgression of symptomsPolygenic risk scoresAlcohol use disorderUse disordersAfrican ancestry individualsGenetic riskRegular useEuropean ancestry individualsEarly onsetMore rapid progressionRegular alcohol useShorter progression timeAge of onsetFirst substance useDiscovery sampleUS inpatientsOnset of problemsOutpatient settingDisease progressionRapid progressionSymptom progressionRisk scoreGenome-wide association studiesPolygenic risk score for problematic alcohol use predicts heavy drinking and alcohol use disorder symptoms in young adulthood after accounting for adolescent alcohol use and parental alcohol use disorder
Wang F, Hicks B, Zhou H, Kranzler H, Gelernter J, Zucker R. Polygenic risk score for problematic alcohol use predicts heavy drinking and alcohol use disorder symptoms in young adulthood after accounting for adolescent alcohol use and parental alcohol use disorder. Drug And Alcohol Dependence 2023, 248: 109909. PMID: 37163864, PMCID: PMC11013565, DOI: 10.1016/j.drugalcdep.2023.109909.Peer-Reviewed Original Research
2022
Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden
Nichter B, Koller D, De Angelis F, Wang J, Girgenti M, Na P, Hill M, Norman S, Krystal J, Gelernter J, Polimanti R, Pietrzak R. Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden. Psychological Medicine 2022, 53: 6325-6333. PMID: 36444557, DOI: 10.1017/s0033291722003646.Peer-Reviewed Original ResearchMeSH KeywordsFemaleGenome-Wide Association StudyHumansMaleRisk FactorsSuicidal IdeationSuicide, AttemptedVeteransConceptsPolygenic risk scoresUS military veteransLifetime suicide attemptsSuicide attemptsTrauma exposureTrauma burdenGenetic liabilityMilitary veteransDrug repurposing analysisPopulation-based sampleCumulative trauma exposureLifetime trauma exposureLow trauma exposureSuicide prediction modelsChronic inflammationInflammatory processNervous system developmentRisk scorePsychiatric characteristicsSuicidal behaviorExposure interactionsLarge genome-wide association studiesHigh levelsVeteransSuicidalityPhenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample
Kember RL, Hartwell EE, Xu H, Rotenberg J, Almasy L, Zhou H, Gelernter J, Kranzler HR. Phenome-wide Association Analysis of Substance Use Disorders in a Deeply Phenotyped Sample. Biological Psychiatry 2022, 93: 536-545. PMID: 36273948, PMCID: PMC9931661, DOI: 10.1016/j.biopsych.2022.08.010.Peer-Reviewed Original ResearchConceptsSubstance use disordersAlcohol use disorderOpioid use disorderPolygenic risk scoresUse disordersCo-occurring psychiatric disordersComprehensive psychiatric interviewSemi-Structured AssessmentElectronic health recordsControl subjectsLow prevalencePsychiatric interviewRisk scorePsychiatric disordersPhenome-wide association analysisDrug dependenceEuropean individualsHealth recordsLifetime cannabisPhenome-wide association studyDisordersAfrican ancestry individualsDSM diagnosesPopulation sampleGenetic liabilityUsing phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder
Wendt FR, Pathak GA, Deak JD, De Angelis F, Koller D, Cabrera-Mendoza B, Lebovitch DS, Levey DF, Stein MB, Kranzler HR, Koenen KC, Gelernter J, Huckins LM, Polimanti R. Using phenotype risk scores to enhance gene discovery for generalized anxiety disorder and posttraumatic stress disorder. Molecular Psychiatry 2022, 27: 2206-2215. PMID: 35181757, PMCID: PMC9133008, DOI: 10.1038/s41380-022-01469-y.Peer-Reviewed Original Research
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 smokingThe addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates
Hatoum AS, Johnson EC, Colbert SMC, Polimanti R, Zhou H, Walters RK, Gelernter J, Edenberg HJ, Bogdan R, Agrawal A. The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates. Neuropsychopharmacology 2021, 47: 1739-1745. PMID: 34750568, PMCID: PMC9372072, DOI: 10.1038/s41386-021-01209-w.Peer-Reviewed Original ResearchDissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
Mullins N, Kang J, Campos AI, Coleman JRI, Edwards AC, Galfalvy H, Levey DF, Lori A, Shabalin A, Starnawska A, Su MH, Watson HJ, Adams M, Awasthi S, Gandal M, Hafferty JD, Hishimoto A, Kim M, Okazaki S, Otsuka I, Ripke S, Ware EB, Bergen AW, Berrettini WH, Bohus M, Brandt H, Chang X, Chen WJ, Chen HC, Crawford S, Crow S, DiBlasi E, Duriez P, Fernández-Aranda F, Fichter MM, Gallinger S, Glatt SJ, Gorwood P, Guo Y, Hakonarson H, Halmi KA, Hwu HG, Jain S, Jamain S, Jiménez-Murcia S, Johnson C, Kaplan AS, Kaye WH, Keel PK, Kennedy JL, Klump KL, Li D, Liao SC, Lieb K, Lilenfeld L, Liu CM, Magistretti PJ, Marshall CR, Mitchell JE, Monson ET, Myers RM, Pinto D, Powers A, Ramoz N, Roepke S, Rozanov V, Scherer SW, Schmahl C, Sokolowski M, Strober M, Thornton LM, Treasure J, Tsuang MT, Witt SH, Woodside DB, Yilmaz Z, Zillich L, Adolfsson R, Agartz I, Air TM, Alda M, Alfredsson L, Andreassen OA, Anjorin A, Appadurai V, Artigas M, Van der Auwera S, Azevedo MH, Bass N, Bau CHD, Baune BT, Bellivier F, Berger K, Biernacka JM, Bigdeli TB, Binder EB, Boehnke M, Boks MP, Bosch R, Braff DL, Bryant R, Budde M, Byrne EM, Cahn W, Casas M, Castelao E, Cervilla JA, Chaumette B, Cichon S, Corvin A, Craddock N, Craig D, Degenhardt F, Djurovic S, Edenberg HJ, Fanous AH, Foo JC, Forstner AJ, Frye M, Fullerton JM, Gatt JM, Gejman PV, Giegling I, Grabe HJ, Green MJ, Grevet EH, Grigoroiu-Serbanescu M, Gutierrez B, Guzman-Parra J, Hamilton SP, Hamshere ML, Hartmann A, Hauser J, Heilmann-Heimbach S, Hoffmann P, Ising M, Jones I, Jones LA, Jonsson L, Kahn RS, Kelsoe JR, Kendler KS, Kloiber S, Koenen KC, Kogevinas M, Konte B, Krebs MO, Landén M, Lawrence J, Leboyer M, Lee PH, Levinson DF, Liao C, Lissowska J, Lucae S, Mayoral F, McElroy SL, McGrath P, McGuffin P, McQuillin A, Medland SE, Mehta D, Melle I, Milaneschi Y, Mitchell PB, Molina E, Morken G, Mortensen PB, Müller-Myhsok B, Nievergelt C, Nimgaonkar V, Nöthen MM, O’Donovan M, Ophoff RA, Owen MJ, Pato C, Pato MT, Penninx BWJH, Pimm J, Pistis G, Potash JB, Power RA, Preisig M, Quested D, Ramos-Quiroga JA, Reif A, Ribasés M, Richarte V, Rietschel M, Rivera M, Roberts A, Roberts G, Rouleau GA, Rovaris DL, Rujescu D, Sánchez-Mora C, Sanders AR, Schofield PR, Schulze TG, Scott LJ, Serretti A, Shi J, Shyn SI, Sirignano L, Sklar P, Smeland OB, Smoller JW, Sonuga-Barke EJS, Spalletta G, Strauss JS, Świątkowska B, Trzaskowski M, Turecki G, Vilar-Ribó L, Vincent JB, Völzke H, Walters JTR, Weickert C, Weickert TW, Weissman MM, Williams LM, Wray NR, Zai CC, Ashley-Koch AE, Beckham JC, Hauser ER, Hauser MA, Kimbrel NA, Lindquist JH, McMahon B, Oslin DW, Qin X, Agerbo E, Børglum A, Breen G, Erlangsen A, Esko T, Gelernter J, Hougaard D, Kessler R, Kranzler H, Li Y, Martin N, McIntosh A, Mors O, Nordentoft M, Olsen C, Porteous D, Ursano R, Wasserman D, Werge T, Whiteman D, Bulik C, Coon H, Demontis D, Docherty A, Kuo P, Lewis G, Mann J, Rentería M, Smith D, Stahl E, Stein D, Streit F, Willour V, Ruderfer D, Wray N, Ripke S, Mattheisen M, Trzaskowski M, Byrne E, Abdellaoui A, Adams M, Agerbo E, Air T, Andlauer T, Bacanu S, Bækvad-Hansen M, Beekman A, Bigdeli T, Binder E, Bryois J, Buttenschøn H, Bybjerg-Grauholm J, Cai N, Castelao E, Christensen J, Clarke T, Coleman J, Colodro-Conde L, Couvy-Duchesne B, Craddock N, Crawford G, Davies G, Degenhardt F, Derks E, Direk N, Dolan C, Dunn E, Eley T, Escott-Price V, Kiadeh F, Finucane H, Foo J, Forstner A, Frank J, Gaspar H, Gill M, Goes F, Gordon S, Weinsheimer S, Wellmann J, Willemsen G, Witt S, Wu Y, Xi H, Yang J, Zhang F, Arolt V, Baune B, Berger K, Boomsma D, Cichon S, Dannlowski U, de Geus E, Depaulo J, Domenici E, Domschke K, Esko T, Grabe H, Hamilton S, Grove J, Hall L, Hansen C, Hansen T, Herms S, Hickie I, Hoffmann P, Homuth G, Horn C, Hottenga J, Hougaard D, Howard D, Ising M, Jansen R, Jones I, Jones L, Jorgenson E, Knowles J, Kohane I, Kraft J, Kretzschmar W, Kutalik Z, Li Q, Lind P, MacIntyre D, MacKinnon D, Maier R, Maier W, Marchini J, Mbarek H, McGrath P, McGuffin P, Medland S, Mehta D, Middeldorp C, Mihailov E, Milaneschi Y, Milani L, Mondimore F, Montgomery G, Mostafavi S, Mullins N, Nauck M, Ng B, Nivard M, Nyholt D, O’Reilly P, Oskarsson H, Hayward C, Heath A, Kendler K, Kloiber S, Lewis C, Li D, Lucae S, Madden P, Magnusson P, Martin N, McIntosh A, Metspalu A, Mors O, Mortensen P, Müller-Myhsok B, Nordentoft M, Nöthen M, O’Donovan M, Paciga S, Pedersen N, Owen M, Painter J, Pedersen C, Pedersen M, Peterson R, Peyrot W, Pistis G, Posthuma D, Quiroz J, Qvist P, Rice J, Riley B, Rivera M, Mirza S, Schoevers R, Schulte E, Shen L, Shi J, Shyn S, Sigurdsson E, Sinnamon G, Smit J, Smith D, Stefansson H, Steinberg S, Streit F, Strohmaier J, Tansey K, Teismann H, Teumer A, Thompson W, Thomson P, Thorgeirsson T, Traylor M, Treutlein J, Trubetskoy V, Uitterlinden A, Umbricht D, Van der Auwera S, van Hemert A, Viktorin A, Visscher P, Wang Y, Webb B, Penninx B, Perlis R, Porteous D, Potash J, Preisig M, Rietschel M, Schaefer C, Schulze T, Smoller J, Stefansson K, Tiemeier H, Uher R, Völzke H, Weissman M, Werge T, Lewis C, Levinson D, Breen G, Børglum A, Sullivan P, Mullins N, Forstner A, O’Connell K, Coombes B, Coleman J, Qiao Z, Als T, Bigdeli T, Børte S, Bryois J, Charney A, Drange O, Gandal M, Hagenaars S, Ikeda M, Kamitaki N, Kim M, Krebs K, Panagiotaropoulou G, Schilder B, Sloofman L, Steinberg S, Trubetskoy V, Winsvold B, Won H, Abramova L, Adorjan K, Agerbo E, Al Eissa M, Albani D, Alliey-Rodriguez N, Anjorin A, Antilla V, Antoniou A, Awasthi S, Baek J, Bækvad-Hansen M, Bass N, Bauer M, Beins E, Bergen S, Birner A, Pedersen C, Bøen E, Boks M, Bosch R, Brum M, Brumpton B, Brunkhorst-Kanaan N, Budde M, Bybjerg-Grauholm J, Byerley W, Cairns M, Casas M, Cervantes P, Clarke T, Cruceanu C, Cuellar-Barboza A, Cunningham J, Curtis D, Czerski P, Dale A, Dalkner N, David F, Degenhardt F, Djurovic S, Dobbyn A, Douzenis A, Elvsåshagen T, Escott-Price V, Ferrier I, Fiorentino A, Foroud T, Forty L, Frank J, Frei O, Freimer N, Frisén L, Gade K, Garnham J, Gelernter J, Pedersen M, Gizer I, Gordon S, Gordon-Smith K, Greenwood T, Grove J, Guzman-Parra J, Ha K, Haraldsson M, Hautzinger M, Heilbronner U, Hellgren D, Herms S, Hoffmann P, Holmans P, Huckins L, Jamain S, Johnson J, Kalman J, Kamatani Y, Kennedy J, Kittel-Schneider S, Knowles J, Kogevinas M, Koromina M, Kranz T, Kranzler H, Kubo M, Kupka R, Kushner S, Lavebratt C, Lawrence J, Leber M, Lee H, Lee P, Levy S, Lewis C, Liao C, Lucae S, Lundberg M, MacIntyre D, Magnusson S, Maier W, Maihofer A, Malaspina D, Maratou E, Martinsson L, Mattheisen M, McGregor N, McGuffin P, McKay J, Medeiros H, Medland S, Millischer V, Montgomery G, Moran J, Morris D, Mühleisen T, O’Brien N, O’Donovan C, Loohuis L, Oruc L, Papiol S, Pardiñas A, Perry A, Pfennig A, Porichi E, Potash J, Quested D, Raj T, Rapaport M, DePaulo J, Regeer E, Rice J, Rivas F, Rivera M, Roth J, Roussos P, Ruderfer D, Sánchez-Mora C, Schulte E, Senner F, Sharp S, Shilling P, Sigurdsson E, Sirignano L, Slaney C, Smeland O, Smith D, Sobell J, Hansen C, Artigas M, Spijker A, Stein M, Strauss J, Świątkowska B, Terao C, Thorgeirsson T, Toma C, Tooney P, Tsermpini E, Vawter P, Vedder H, Walters J, Witt S, Xi S, Xu W, Yang J, Young A, Young H, Zandi P, Zhou H, Zillich L, Psychiatry H, 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, 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, Adan R, Alfredsson L, Ando T, Andreassen O, Aschauer H, Baker J, Bencko V, Bergen A, Berrettini W, Birgegård A, Boden J, Boehm I, Boni C, Perica V, Brandt H, Breen G, Bryois J, Buehren K, Bulik C, Burghardt R, Carlberg L, Cassina M, Cichon S, Clementi M, Coleman J, Cone R, Courtet P, Crawford S, Crow S, Crowley J, Danner U, Davis O, de Zwaan M, Dedoussis G, Degortes D, DeSocio J, Dick D, Dikeos D, Dina C, Dmitrzak-Weglarz M, Martinez E, Duncan L, Egberts K, Marshall C, Martin N, Mattheisen M, Mattingsdal M, McDevitt S, McGuffin P, Medland S, Metspalu A, Meulenbelt I, Micali N, Mitchell J, Mitchell K, Monteleone P, Monteleone A, Montgomery G, Mortensen P, Munn-Chernoff M, Nacmias B, Navratilova M, Ntalla I, Olsen M, Ophoff R, O’Toole J, Padyukov L, Palotie A, Pantel J, Papezova H, Parker R, Pearson J, Pedersen N, Ehrlich S, Escaramís G, Esko T, Espeseth T, Estivill X, Farmer A, Favaro A, Fernández-Aranda F, Fichter M, Fischer K, Floyd J, Föcker M, Foretova L, Forstner A, Forzan M, Franklin C, Gallinger S, Gambaro G, Gaspar H, Giegling I, Giuranna J, Giusti-Rodríquez P, Gonidakis F, Gordon S, Gorwood P, Mayora M, Grove J, Guillaume S, Guo Y, Hakonarson H, Halmi K, Hanscombe K, Hatzikotoulas K, Hauser E, Hebebrand J, Helder S, Henders A, Herms S, Herpertz-Dahlmann B, Herzog W, Hinney A, Horwood L, Hübel C, Petersen L, Pinto D, Purves K, Raevuori A, Ramoz N, Reichborn-Kjennerud T, Ricca V, Ripatti S, Ripke S, Ritschel F, Roberts M, Rujescu D, Rybakowski F, Santonastaso P, Scherag A, Scherer S, Schmidt U, Schork N, Schosser A, Seitz J, Slachtova L, Slagboom P, Landt M, Slopien A, Soranzo N, Sorbi S, Southam L, Steen V, Strober M, Huckins L, Hudson J, Imgart H, Inoko H, Janout V, Jiménez-Murcia S, Johnson C, Jordan J, Julià A, Kalsi G, Kaminská D, Kaplan A, Kaprio J, Karhunen L, Karwautz A, Kas M, Kaye W, Kennedy M, Kennedy M, Keski-Rahkonen A, Kiezebrink K, Kim Y, Kirk K, Klareskog L, Klump K, Knudsen G, Landén M, Larsen J, Le Hellard S, Leppä V, Li D, Lichtenstein P, Lilenfeld L, Lin B, Lissowska J, Lundervold A, Luykx J, Magistretti P, Maj M, Mannik K, Marsal S, Stuber G, Sullivan P, Świątkowska B, Szatkiewicz J, Tachmazidou I, Tenconi E, Thornton L, Tortorella A, Tozzi F, Treasure J, Tsitsika A, Tyszkiewicz-Nwafor M, Tziouvas K, van Elburg A, van Furth E, Wade T, Wagner G, Walton E, Watson H, Werge T, Whiteman D, Wichmann H, Widen E, Woodside D, Yao S, Yilmaz Z, Zeggini E, Zerwas S, Zipfel S, Witt S, Streit F, Jungkunz M, Frank J, Awasthi S, Treutlein J, Dietl L, Schwarze C, Dahmen N, Schott B, Nöthen M, Ripke S, Mobascher A, Rujescu D, Lieb K, Roepke S, Schmahl C, Bohus M, Rietschel M, Crivelli S, Dennis M, Harvey P, Carter B, Huffman J, Jacobson D, Madduri R, Olsen C, Pestian J, Gaziano J, Muralidhar S, Ramoni R, Beckham J, Chang K, O’Donnell C, Tsao P, Breeling J, Huang G, Romero J, Muralidhar S, Moser J, Whitbourne S, Brewer J, Aslan M, Connor T, Argyres D, Tsao P, Gaziano J, Stephens B, Brophy M, Humphries D, Selva L, Do N, Shayan S, Cho K, O’Donnell C, O’Donnell C, Pyarajan S, Tsao P, Cho K, Pyarajan S, Hauser E, Sun Y, Zhao H, Wilson P, McArdle R, Dellitalia L, Mattocks K, Harley J, Zablocki C, Whittle J, Jacono F, Beckham J, Gutierrez S, Gibson G, Hammer K, Kaminsky L, Villareal G, Kinlay S, Xu J, Hamner M, Mathew R, Bhushan S, Iruvanti P, Godschalk M, Ballas Z, Ivins D, Mastorides S, Moorman J, Gappy S, Klein J, Ratcliffe N, Florez H, Okusaga O, Murdoch M, Sriram P, Yeh S, Tandon N, Jhala D, Aguayo S, Cohen D, Sharma S, Liangpunsakul S, Oursler K, Whooley M, Ahuja S, Constans J, Meyer P, Greco J, Rauchman M, Servatius R, Gaddy M, Wallbom A, Morgan T, Stapley T, Sherman S, Ross G, Tsao P, Strollo P, Boyko E, Meyer L, Gupta S, Huq M, Fayad J, Hung A, Lichy J, Hurley R, Robey B, Striker R. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors. Biological Psychiatry 2021, 91: 313-327. PMID: 34861974, PMCID: PMC8851871, DOI: 10.1016/j.biopsych.2021.05.029.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenetic architecturePsychiatric disordersGenetic correlationsRisk factorsGenome-wide significanceDivergent genetic architecturesGWAS summary statisticsShared genetic architectureStrong genetic correlationIntergenic lociSuicide attemptsReproductive traitsKnown Risk FactorsRisk lociPoor general healthChromosome 7Association studiesRelated psychiatric disordersMillion Veteran ProgramSuicide attempt casesLow socioeconomic statusLociNonfatal suicide attemptsGenetic effectsPolygenic risk for major depression is associated with lifetime suicide attempt in US soldiers independent of personal and parental history of major depression
Stein MB, Jain S, Campbell‐Sills L, Ware EB, Choi KW, He F, Ge T, Gelernter J, Smoller JW, Kessler RC, Ursano RJ. Polygenic risk for major depression is associated with lifetime suicide attempt in US soldiers independent of personal and parental history of major depression. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2021, 186: 469-475. PMID: 34288400, PMCID: PMC8692314, DOI: 10.1002/ajmg.b.32868.Peer-Reviewed Original ResearchConceptsMajor depressive disorderLifetime suicide attemptsParental historySuicide attemptsMajor depressionMDD-PRSMultivariable modelLifetime historyMajor public health problemIncident suicide attemptsPolygenic riskPublic health problemUS Army soldiersRisk stratificationDepressive disorderPolygenic risk scoresRisk scoreSecond cohortHealth problemsCommon genetic variantsFirst cohortPersonal historyCohortGenetic variantsArmy soldiersGenome-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 leadsMulti-environment gene interactions linked to the interplay between polysubstance dependence and suicidality
Polimanti R, Levey DF, Pathak GA, Wendt FR, Nunez YZ, Ursano RJ, Kessler RC, Kranzler HR, Stein MB, Gelernter J. Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality. Translational Psychiatry 2021, 11: 34. PMID: 33431810, PMCID: PMC7801457, DOI: 10.1038/s41398-020-01153-1.Peer-Reviewed Original ResearchConceptsSuicidal ideationPolysubstance dependenceSuicide attemptsOdds ratioGene-environment interactionsYale-PennMultivariate logistic regressionImportant risk factorMultivariate gene-environment interactionsMental health risksOpioid dependenceRisk factorsNicotine dependenceSuicidality outcomesCocaine dependenceLogistic regressionSubstance dependenceSuicidalityCohortLifetime suicidalityLinear mixed modelsMultiple substancesArmy STARRSArmy personnelHealth risks
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 traitsStatusSyndromePolygenic risk for autism spectrum disorder associates with anger recognition in a neurodevelopment-focused phenome-wide scan of unaffected youths from a population-based cohort
Wendt FR, Carvalho CM, Pathak GA, Gelernter J, Polimanti R. Polygenic risk for autism spectrum disorder associates with anger recognition in a neurodevelopment-focused phenome-wide scan of unaffected youths from a population-based cohort. PLOS Genetics 2020, 16: e1009036. PMID: 32941431, PMCID: PMC7523983, DOI: 10.1371/journal.pgen.1009036.Peer-Reviewed Original Research
2018
GWAS and network analysis of co‐occurring nicotine and alcohol dependence identifies significantly associated alleles and network
Xiang B, Yang B, Zhou H, Kranzler H, Gelernter J. GWAS and network analysis of co‐occurring nicotine and alcohol dependence identifies significantly associated alleles and network. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2018, 180: 3-11. PMID: 30488612, PMCID: PMC6918694, DOI: 10.1002/ajmg.b.32692.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismAllelesBlack or African AmericanComorbidityEthanolFemaleG(M2) Activator ProteinGene FrequencyGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedNicotinePolymorphism, Single NucleotideProtein Interaction MapsRisk FactorsTobacco Use DisorderWhite PeopleConceptsGene subnetworksProtein-protein interaction (PPI) network analysisGenome-wide significant variantsInteraction network analysisGene-set analysisFunctional enrichment analysisSignificant SNPsQuantitative lociNerve growth factor pathwayGene enrichmentEnrichment analysisNetwork analysisGenetic traitsGrowth factor pathwaysRisk genesSignificant variantsGenesStudy of AddictionSNPsFactor pathwayGM2AAmphetamine addictionGenetic riskGWASSubnetworksRisk Locus Identification Ties Alcohol Withdrawal Symptoms to SORCS2
Smith AH, Ovesen PL, Skeldal S, Yeo S, Jensen KP, Olsen D, Diazgranados N, Zhao H, Farrer LA, Goldman D, Glerup S, Kranzler HR, Nykjær A, Gelernter J. Risk Locus Identification Ties Alcohol Withdrawal Symptoms to SORCS2. Alcohol Clinical And Experimental Research 2018, 42: 2337-2348. PMID: 30252935, PMCID: PMC6317871, DOI: 10.1111/acer.13890.Peer-Reviewed Original ResearchConceptsAlcohol withdrawalEpigenomic data setsGenome-wide association studiesWide significant findingsLife-threatening seizuresAlcohol withdrawal symptomsTop association signalsTissue-specific activityNeural lineage cellsGenetic risk factorsHarmful alcohol useAssociation signalsRegulatory elementsBioinformatics analysisStress hormone levelsAlcohol cessationChromosome 4Neurotrophic factorWithdrawal symptomsRisk factorsEthanol exposureHormone levelsAssociation studiesNervous systemAdditional genotypingGenome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression
Zhou H, Cheng Z, Bass N, Krystal JH, Farrer LA, Kranzler HR, Gelernter J. Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression. Translational Psychiatry 2018, 8: 208. PMID: 30287806, PMCID: PMC6172277, DOI: 10.1038/s41398-018-0258-8.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide association study identifiesRisk genesTop risk genesCalcium ion bindingGenomes reference panelFast excitatory synaptic transmissionGenetic risk variantsGenetic basisEnrichment analysisAssociation studiesExome arrayCell adhesionRisk variantsGenesReference panelGenetic riskAMPA-sensitive glutamate receptorsIntronic variantsIon bindingBiological mechanismsConditional analysisGRIA4Excitatory synaptic transmissionSynaptic transmissionBiochemical, demographic, and self-reported tobacco-related predictors of the acute heart rate response to nicotine in smokers
Jensen KP, Valentine G, Buta E, DeVito EE, Gelernter J, Sofuoglu M. Biochemical, demographic, and self-reported tobacco-related predictors of the acute heart rate response to nicotine in smokers. Pharmacology Biochemistry And Behavior 2018, 173: 36-43. PMID: 30107183, PMCID: PMC6125200, DOI: 10.1016/j.pbb.2018.08.004.Peer-Reviewed Original ResearchConceptsAcute heart rate responseHeart rate responseNicotine infusionHigher nicotine metabolite ratioTobacco harm reduction approachesRate responseGreater withdrawal symptomsNicotine metabolite ratioBlood-based biomarkersNicotine delivery systemsWarrants further investigationHarm reduction approachWithdrawal symptomsCardiovascular functionLower nicotine levelsTobacco useMetabolite ratiosNicotine levelsSmokeless productsHigher cortisolSmokersHR effectsStimulatory effectNicotineDemographic characteristics