2025
Linking prolonged childhood and adolescent loneliness to schizophrenia spectrum disorders: results from EU-GEI study.
Andreu-Bernabeu Á, González-Peñas J, Mora A, Bernardo M, Mezquida G, Amoretti S, Bobes J, Saiz P, García-Portilla M, Sanjuan J, Santos J, Jiménez-López E, Arrojo M, Carracedo A, Parellada M, Maric N, Atbaşoğlu C, Üçok A, Alptekin K, Saka M, Pries L, O'Donovan M, van Os J, Rutten B, Delespaul P, Guloksuz S, Arango C, Díaz-Caneja C. Linking prolonged childhood and adolescent loneliness to schizophrenia spectrum disorders: results from EU-GEI study. The British Journal Of Psychiatry 2025, 1-9. PMID: 40519115, DOI: 10.1192/bjp.2025.100.Peer-Reviewed Original ResearchGene-environment interactionsGenetic riskSchizophrenia spectrum disordersAdverse mental health outcomesGenetic liabilityAssociated with higher oddsPolygenic risk scoresIdentification of high-risk individualsMental health outcomesRelative excess riskHigh-risk individualsEU-GEILogistic regression modelsHealth outcomesExcess riskHigher oddsPrevention strategiesVulnerable populationsRisk scoreRegression modelsLonelinessEarly identificationLong-term effectsWorsening symptomsAssociated with psychosisIntegrating HiTOP and RDoC frameworks part II: shared and distinct biological mechanisms of externalizing and internalizing psychopathology
Davis C, Khan Y, Toikumo S, Jinwala Z, Boomsma D, Levey D, Gelernter J, Kember R, Kranzler H. Integrating HiTOP and RDoC frameworks part II: shared and distinct biological mechanisms of externalizing and internalizing psychopathology. Psychological Medicine 2025, 55: e137. PMID: 40340892, PMCID: PMC12094665, DOI: 10.1017/s0033291725000819.Peer-Reviewed Original ResearchConceptsDrug repurposing analysisAssociated with reduced gray matter volumeHierarchical Taxonomy of PsychopathologyGenome-wide association studiesTaxonomy of PsychopathologyResearch Domain CriteriaTissue-specific expression patternsAspects of psychopathologyGray matter volumeSingle-cell RNA sequencing dataGene identification methodsMagnetic resonance imaging dataMulti-omics approachRNA sequencing dataBrain cell typesHiTOP frameworkInternalizing psychopathologyPhysical health conditionsPsychopathological spectrumSubcallosal cortexGene annotationMatter volumeGenomic insightsSequence dataGenetic liabilityIntegrating HiTOP and RDoC frameworks Part I: Genetic architecture of externalizing and internalizing psychopathology
Davis C, Khan Y, Toikumo S, Jinwala Z, Boomsma D, Levey D, Gelernter J, Kember R, Kranzler H. Integrating HiTOP and RDoC frameworks Part I: Genetic architecture of externalizing and internalizing psychopathology. Psychological Medicine 2025, 55: e138. PMID: 40336358, PMCID: PMC12094639, DOI: 10.1017/s0033291725000856.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesMultivariate genome-wide association studyGenetic architectureComorbid forms of psychopathologyHierarchical Taxonomy of PsychopathologyBivariate causal mixture modelResearch Domain CriteriaTaxonomy of PsychopathologyPsychiatric classification systemsConfirmatory factor modelsInternalizing psychopathologyComorbid formsGenetic liabilityPsychopathologyTwo-factorHierarchical taxonomyModerate genetic correlationLatent factorsAssociation studiesBiological basisHiTOPReference panelGenetic underpinningsFactor modelGenetic variantsIdentification of risk variants and cross-disorder pleiotropy through multi-ancestry genome-wide analysis of alcohol use disorder
Icick R, Shadrin A, Holen B, Karadag N, Parker N, O’Connell K, Frei O, Bahrami S, Høegh M, Lagerberg T, Cheng W, Seibert T, Djurovic S, Dale A, Zhou H, Edenberg H, Gelernter J, Smeland O, Hindley G, Andreassen O. Identification of risk variants and cross-disorder pleiotropy through multi-ancestry genome-wide analysis of alcohol use disorder. Nature Mental Health 2025, 3: 253-265. PMID: 40322774, PMCID: PMC12048032, DOI: 10.1038/s44220-024-00353-8.Peer-Reviewed Original ResearchAlcohol use disorderGenome-wide association studiesUse disorderAssociation studiesMulti-ancestry genome-wide association studyEtiology of alcohol use disordersIdentification of risk variantsAlcohol use disorder phenotypesGenome-wide significant lociAlcohol use disorder riskMapped to genesComplications of alcohol usePotential drug targetsAlcohol phenotypesCross-disorderPolygenic overlapPositive genetic correlationSignificant lociGenetic architectureGenetic liabilityGenetic lociBrain regionsRisk variantsGenetic studiesImmune-related genesA genetic exploration of the relationship between posttraumatic stress disorder and cardiovascular diseases
Lukas E, Veeneman R, Smit D, Ahluwalia T, Vermeulen J, Pathak G, Polimanti R, Verweij K, Treur J. A genetic exploration of the relationship between posttraumatic stress disorder and cardiovascular diseases. Translational Psychiatry 2025, 15: 1. PMID: 39755697, PMCID: PMC11700205, DOI: 10.1038/s41398-024-03197-z.Peer-Reviewed Original ResearchPosttraumatic stress disorderMendelian randomizationCardiovascular diseaseCausal pathwaysData of genome-wide association studiesGenetic liabilityMultivariable Mendelian randomizationWaist-to-hip ratioPotential mediatorsWaist-to-hipRisk of cardiovascular diseaseGenome-wide association studiesPotential causal pathwaysPrevent Cardiovascular DiseaseStress disorderIncreased risk of cardiovascular diseaseGenomic structural equationSignificant genetic correlationsPsychosocial factorsEffects of posttraumatic stress disorderAssociation studiesIncreased riskPosttraumatic stress disorder patientsCausal effectsTraumatic events
2024
Polygenic Risk Scores and Twin Concordance for Schizophrenia and Bipolar Disorder
Song J, Pasman J, Johansson V, Kuja-Halkola R, Harder A, Karlsson R, Lu Y, Kowalec K, Pedersen N, Cannon T, Hultman C, Sullivan P. Polygenic Risk Scores and Twin Concordance for Schizophrenia and Bipolar Disorder. JAMA Psychiatry 2024, 81: 1246-1252. PMID: 39196586, PMCID: PMC11359115, DOI: 10.1001/jamapsychiatry.2024.2406.Peer-Reviewed Original ResearchPolygenic risk scoresGenome-wide association studiesSwedish Twin RegistryBipolar disorderCase-control studyTwin concordanceTwin heritabilityLevels of polygenic risk scoreTwin RegistrySwedish national register dataCompare polygenic risk scoresRisk scoreNational register dataHeritable psychiatric disorderAffected co-twinsPairs of twinsPsychosis phenotypeIllness vulnerabilityClinical InterviewPsychiatric disordersGenetic liabilityMain OutcomesStructural equation modelingPsychosisSchizophreniaF95. LOCAL ANCESTRY-AWARE META-ANALYSIS OF GENOME-WIDE ASSOCIATION STUDIES FOR ALCOHOL CONSUMPTION IN LATIN AMERICAN POPULATIONS
Martinez-Magana J, Atkinson E, Giusti-Rodriguez P, Santoro M, Wassertheil-Smoller S, Daviglus M, Perreira K, Nicolini H, Pereira A, Belangero S, Moyses-Oliveira M, Tucker K, Ordovas J, Villatoro-Velazquez J, Montalvo-Ortiz J. F95. LOCAL ANCESTRY-AWARE META-ANALYSIS OF GENOME-WIDE ASSOCIATION STUDIES FOR ALCOHOL CONSUMPTION IN LATIN AMERICAN POPULATIONS. European Neuropsychopharmacology 2024, 87: 256. DOI: 10.1016/j.euroneuro.2024.08.506.Peer-Reviewed Original ResearchGenome-wide association studiesGenome-wide association study studiesAncestry-specific effectsIntergenic variantAlcohol consumptionAncestry-specific lociNative-American ancestryFrequency of alcohol consumptionAssociated with alcohol consumptionMeta-analysisLocal ancestryAdmixed populationsGWA studiesGenomic backgroundAssociation studiesSLIT3 geneMAGI1 genesGenomics ConsortiumGenetic associationGenesLatin American populationsAfrican ancestryGenetic liabilityUnited StatesAncestryAssociations Between Genetic Risk, Physical Activities, and Distressing Psychotic-like Experiences
Ku B, Yuan Q, Arias-Magnasco A, Lin B, Walker E, Druss B, Ren J, van Os J, Guloksuz S. Associations Between Genetic Risk, Physical Activities, and Distressing Psychotic-like Experiences. Schizophrenia Bulletin 2024, sbae141. PMID: 39171674, DOI: 10.1093/schbul/sbae141.Peer-Reviewed Original ResearchPhysical activityPRS-SCZDistressing psychotic-like experiencesPsychotic-like experiencesDevelopment of psychosisMechanisms of physical activityGenetic liabilityParticipants of European ancestryPolygenic risk scoresIncome-to-needs ratioBody mass indexAssociated with trajectoriesAssociated with less riskAdolescent Brain Cognitive Development StudyAssociated with impaired functionFamily history of psychosisLinear mixed modelsGeneralized linear mixed modelsCognitive Development StudyHistory of psychosisEuropean ancestryGenetic riskFamily historyMass indexRisk scoreApplication of polygenic scores to a deeply phenotyped sample enriched for substance use disorders reveals extensive pleiotropy with psychiatric and somatic traits
Hartwell E, Jinwala Z, Milone J, Ramirez S, Gelernter J, Kranzler H, Kember R. Application of polygenic scores to a deeply phenotyped sample enriched for substance use disorders reveals extensive pleiotropy with psychiatric and somatic traits. Neuropsychopharmacology 2024, 49: 1958-1967. PMID: 39043921, PMCID: PMC11480112, DOI: 10.1038/s41386-024-01922-2.Peer-Reviewed Original ResearchSubstance use disordersPost-traumatic stress disorderGeneralized anxiety disorderGenetic liabilityPolygenic scoresBipolar disorderSubstance use phenotypesSomatic traitsBody mass indexSubstance use categoriesEffect of genetic liabilityAnxiety disordersDepression-relatedDepressive disorderApplication of polygenic scoresStress disorderPsychiatric disordersPsychiatric phenotypesUse disorderPhenome-wide association studyGenetic influencesCross-sectional sampleMedical illnessPrecision medicine effortsPhenotyped sampleGenetically Informed Study Highlights Income-Independent Effect of Schizophrenia Liability on Mental and Physical Health
Kouakou M, Cabrera-Mendoza B, Pathak G, Cannon T, Polimanti R. Genetically Informed Study Highlights Income-Independent Effect of Schizophrenia Liability on Mental and Physical Health. Schizophrenia Bulletin 2024, 51: 85-94. PMID: 38848523, PMCID: PMC11661948, DOI: 10.1093/schbul/sbae093.Peer-Reviewed Original ResearchMultivariable Mendelian randomizationMR analysisMedical endpointsMultivariable MR analysisNegative health outcomesSubstance usePsychiatric Genomics ConsortiumHigh-risk individualsFinnGen participantsMendelian randomizationMultiple testing correctionSocioeconomic inequalitiesHealth outcomesBonferroni multiple testing correctionUK BiobankSocioeconomic differencesPhysical healthMental healthAnalysis of schizophreniaGenetic liabilityAdjustment disorderHousehold incomeLife expectancyTesting correctionPersonality disorderEstimating the direct effects of the genetic liabilities to bipolar disorder, schizophrenia, and behavioral traits on suicide attempt using a multivariable Mendelian randomization approach
Cabrera-Mendoza B, Aydin N, Fries G, Docherty A, Walss-Bass C, Polimanti R. Estimating the direct effects of the genetic liabilities to bipolar disorder, schizophrenia, and behavioral traits on suicide attempt using a multivariable Mendelian randomization approach. Neuropsychopharmacology 2024, 49: 1383-1391. PMID: 38396255, DOI: 10.1038/s41386-024-01833-2.Peer-Reviewed Original ResearchAssociated with higher oddsPsychiatric Genomics ConsortiumSubstance use disordersSocioeconomic factorsMendelian randomizationBipolar disorderGenetic liabilitySuicide attemptsHigher oddsTwo-sample Mendelian randomizationGenetic liability to bipolar disorderEffects of mental distressUK Biobank (UKBLiability to bipolar disorderMultivariable MR approachMendelian randomization approachComprehensive mental health assessmentGenome-wide association dataRisk of psychiatric disordersMental health assessmentBehavioral traitsAssociated with lonelinessHigh-risk individualsMental distressContext of SAGenomic insights into the comorbidity between type 2 diabetes and schizophrenia
Arruda A, Khandaker G, Morris A, Smith G, Huckins L, Zeggini E. Genomic insights into the comorbidity between type 2 diabetes and schizophrenia. Schizophrenia 2024, 10: 22. PMID: 38383672, PMCID: PMC10881980, DOI: 10.1038/s41537-024-00445-5.Peer-Reviewed Original ResearchBody mass indexType 2 diabetesType 2 diabetes riskEffect of body mass indexPutative effector genesN-methyl-D-aspartatePublic health challengeIncreased Body Mass IndexLipid-related pathwaysRisk-increasing effectMulti-omics dataMendelian randomizationPotential causal relationshipGene expression studiesDirection of effectMental healthDrug repurposing opportunitiesAssociation signalsGenomic lociGenomic insightsHealth challengesEffector genesGenetic liabilityMass indexExpression studiesPolygenic 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 analysisGenetic Liability to Posttraumatic Stress Disorder Symptoms and Its Association With Cardiometabolic and Respiratory Outcomes
Pathak G, Singh K, Choi K, Fang Y, Kouakou M, Lee Y, Zhou X, Fritsche L, Wendt F, Davis L, Polimanti R. Genetic Liability to Posttraumatic Stress Disorder Symptoms and Its Association With Cardiometabolic and Respiratory Outcomes. JAMA Psychiatry 2024, 81: 34-44. PMID: 37910111, PMCID: PMC10620678, DOI: 10.1001/jamapsychiatry.2023.4127.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderBody mass indexMass General BrighamPTSD symptom severityElectronic health recordsSymptom severityRespiratory outcomesMass indexRisk factorsMedical outcomesHealth outcomesMendelian randomizationDisease categoriesGenetic liabilityMeta-analyzed associationsSignificant medical outcomesNonspecific chest painC-reactive proteinMental health disordersUK BiobankMultivariable Mendelian randomizationPosttraumatic stress disorder (PTSD) symptomsChest painCardiac dysrhythmiasTobacco smoking
2023
MULTI-ANCESTRY PHENOME-WIDE ASSOCIATION ANALYSES OF GENETIC LIABILITY FOR PROBLEMATIC ALCOHOL USE
Kember R, Johnson J, Johnston K, Lee H, Xu J, Davis L, Smoller J, Mallard T, Huckins L, Sanchez-Roige S, Kranzler H, Gelernter J, Zhou H. MULTI-ANCESTRY PHENOME-WIDE ASSOCIATION ANALYSES OF GENETIC LIABILITY FOR PROBLEMATIC ALCOHOL USE. European Neuropsychopharmacology 2023, 75: s10. DOI: 10.1016/j.euroneuro.2023.08.027.Peer-Reviewed Original ResearchMultivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders
Hatoum A, Colbert S, Johnson E, Huggett S, Deak J, Pathak G, Jennings M, Paul S, Karcher N, Hansen I, Baranger D, Edwards A, Grotzinger A, Tucker-Drob E, Kranzler H, Davis L, Sanchez-Roige S, Polimanti R, Gelernter J, Edenberg H, Bogdan R, Agrawal A. Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders. Nature Mental Health 2023, 1: 210-223. PMID: 37250466, PMCID: PMC10217792, DOI: 10.1038/s44220-023-00034-y.Peer-Reviewed Original ResearchGenome-wide associationGenetic risk lociIndependent single nucleotide polymorphismsProblematic tobacco useSingle nucleotide polymorphismsRisk lociHigh polygenicityLociReceptor geneAddiction risk factorsPolygenic risk scoresEuropean descentPolygenicityGenesSummary statisticsSubstance use disordersSomatic conditionsAncestryRegulationConfersUse disordersPolymorphismGenetic liabilityDopamine regulationPDE4B
2022
Associations Between Cannabis Use, Polygenic Liability for Schizophrenia, and Cannabis-related Experiences in a Sample of Cannabis Users
Johnson E, Colbert S, Jeffries P, Tillman R, Bigdeli T, Karcher N, Chan G, Kuperman S, Meyers J, Nurnberger J, Plawecki M, Degenhardt L, Martin N, Kamarajan C, Schuckit M, Murray R, Dick D, Edenberg H, D’Souza D, Di Forti M, Porjesz B, Nelson E, Agrawal A. Associations Between Cannabis Use, Polygenic Liability for Schizophrenia, and Cannabis-related Experiences in a Sample of Cannabis Users. Schizophrenia Bulletin 2022, 49: 778-787. PMID: 36545904, PMCID: PMC10154717, DOI: 10.1093/schbul/sbac196.Peer-Reviewed Original ResearchConceptsCannabis useAlcohol use disorderCognitive difficultiesSchizophrenia polygenic risk scoresFirst cannabis useDaily cannabis useCannabis usersSocial withdrawalUnusual experiencesCannabis involvementPolygenic risk scoresExpected directionGenetic riskUse disordersIndependent replication sampleLike experiencesGenetic liabilityCannabisSchizophreniaPolygenic riskPolygenic liabilityReplication sampleExperienceAnalytic sampleDisordersGenetic 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 ResearchConceptsPolygenic 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 liability
2021
Host Genetic Liability for Severe COVID-19 Associates with Alcohol Drinking Behavior and Diabetic Outcomes in Participants of European Descent
Wendt FR, De Lillo A, Pathak GA, De Angelis F, Initiative C, Polimanti R. Host Genetic Liability for Severe COVID-19 Associates with Alcohol Drinking Behavior and Diabetic Outcomes in Participants of European Descent. Frontiers In Genetics 2021, 12: 765247. PMID: 34966408, PMCID: PMC8711039, DOI: 10.3389/fgene.2021.765247.Peer-Reviewed Original ResearchRisk factorsPotential long-term health effectsAlcohol drinking statusLong-term health effectsCOVID-19 risk locusCOVID-19 infectionCOVID-19 outcomesAlcohol drinking behaviorCOVID-19 epidemiologyMetformin useDiabetic outcomesHematologic biomarkersLong-term consequencesDrinking statusDepressive symptomsHealth effectsSevere responseEuropean descentDrinking behaviorGenetic liabilityInfectionMolecular mechanismsOutcomesRisk lociGenetic contribution
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