2024
Integrating genome-wide information and wearable device data to explore the link of anxiety and antidepressants with pulse rate variability
Friligkou E, Koller D, Pathak G, Miller E, Lampert R, Stein M, Polimanti R. Integrating genome-wide information and wearable device data to explore the link of anxiety and antidepressants with pulse rate variability. Molecular Psychiatry 2024, 1-7. PMID: 39558002, DOI: 10.1038/s41380-024-02836-7.Peer-Reviewed Original ResearchPolygenic risk scoresMendelian randomizationReuptake inhibitorsOne-sample Mendelian randomizationElectronic health record dataOne-sample MRHealth record dataMillion Veteran ProgramPotential causal effectSerotonin reuptake inhibitorsNorepinephrine reuptake inhibitorsGenome-wide association studiesEffects of anxietyImpact of anxietyWearable device dataUK BiobankVeteran ProgramAntidepressant prescriptionsAnxiety disordersAntidepressant medicationAntidepressant useAntidepressant exposureTricyclic antidepressantsPRS-CSRecord dataPosttraumatic Stress Disorder, Obesity, and Accelerated Epigenetic Aging Among US Military Veterans
Fischer I, Na P, Nagamatsu S, Jeste D, Cabrera-Mendoza B, Montalvo-Ortiz J, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Posttraumatic Stress Disorder, Obesity, and Accelerated Epigenetic Aging Among US Military Veterans. JAMA Psychiatry 2024, 81 PMID: 39476130, DOI: 10.1001/jamapsychiatry.2024.3403.Peer-Reviewed Original ResearchAssociation of deployment characteristics and exposures with persistent ill health among 1990-1991 Gulf War veterans in the VA Million Veteran Program
Steele L, Quaden R, Ahmed S, Harrington K, Duong L, Ko J, Gifford E, Polimanti R, Gaziano J, Aslan M, Helmer D, Hauser E. Association of deployment characteristics and exposures with persistent ill health among 1990-1991 Gulf War veterans in the VA Million Veteran Program. Environmental Health 2024, 23: 92. PMID: 39456027, PMCID: PMC11520114, DOI: 10.1186/s12940-024-01118-7.Peer-Reviewed Original ResearchConceptsMillion Veteran ProgramVA Million Veteran ProgramGulf War veteransIll healthHealth outcomesGulf War IllnessVeteran ProgramMilitary characteristicsWar veteransChronic ill healthCenters for Disease Control and Prevention criteriaGulf War serviceEvaluation of genetic factorsGulf War exposureVeterans' healthPopulation of U.S.Pyridostigmine bromide pillsHealthcare providersWartime exposuresGulf War deploymentResultsThe final cohortVeteran cohortDeployment exposuresHealth problemsVeteransGene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study
Friligkou E, Løkhammer S, Cabrera-Mendoza B, Shen J, He J, Deiana G, Zanoaga M, Asgel Z, Pilcher A, Di Lascio L, Makharashvili A, Koller D, Tylee D, Pathak G, Polimanti R. Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study. Nature Genetics 2024, 56: 2036-2045. PMID: 39294497, DOI: 10.1038/s41588-024-01908-2.Peer-Reviewed Original ResearchGenome-wide association studiesAnxiety disordersAssociation studiesMulti-ancestry genome-wide association studyPathogenesis of anxiety disordersHeritability of anxietyLocal genetic correlationProteome-wide analysisIndividuals of European descentAssociated with anxietyMulti-omics informationWidespread pleiotropyTranscriptome-widePolygenic risk scoresBipolar disorderAncestry-specificGene discoveryContinental groupsLimbic systemEast Asian groupsBiological insightsAnxietyEntorhinal cortexPhysical health domainBrain-specificAssociation patterns of antisocial personality disorder across substance use disorders
Low A, Stiltner B, Nunez Y, Adhikari K, Deak J, Pietrzak R, Kranzler H, Gelernter J, Polimanti R. Association patterns of antisocial personality disorder across substance use disorders. Translational Psychiatry 2024, 14: 346. PMID: 39198385, PMCID: PMC11358160, DOI: 10.1038/s41398-024-03054-z.Peer-Reviewed Original ResearchConceptsAntisocial personality disorderSubstance use disordersPersonality disorderUse disorderAssociation of antisocial personality disorderPresence of antisocial personality disorderPrevalence of antisocial personality disorderHazardous useDSM-5 SUD diagnosesSubstance use disorder severityDiagnostic criteriaInteraction effects with sexTobacco use disorderDSM-5Association of alcoholSUD diagnosisDisordersCocaineRacial/ethnic backgroundsIndividualsCocUDSeverityCannabisAssociation patternsAssociationUsing Medical Records to Investigate the Genetics of Treatment-Resistant Depression Across Health Care Systems
Polimanti R. Using Medical Records to Investigate the Genetics of Treatment-Resistant Depression Across Health Care Systems. American Journal Of Psychiatry 2024, 181: 569-571. PMID: 38946279, DOI: 10.1176/appi.ajp.20240377.Peer-Reviewed Original ResearchGenetically 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, sbae093. PMID: 38848523, 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 disorderDistinguishing vulnerability and resilience to posttraumatic stress disorder evaluating traumatic experiences, genetic risk and electronic health records
Løkhammer S, Koller D, Wendt F, Choi K, He J, Friligkou E, Overstreet C, Gelernter J, Hellard S, Polimanti R. Distinguishing vulnerability and resilience to posttraumatic stress disorder evaluating traumatic experiences, genetic risk and electronic health records. Psychiatry Research 2024, 337: 115950. PMID: 38744179, PMCID: PMC11156529, DOI: 10.1016/j.psychres.2024.115950.Peer-Reviewed Original ResearchElectronic health recordsPosttraumatic stress disorderHealth recordsPTSD vulnerabilityUK Biobank (UKBPhenome-wide association studyRisk scorePhenotype risk scoreUs Research ProgramPolygenic risk scoresStress disorderAoU participantsUKB participantsPresence of posttraumatic stress disorderTrauma burdenGenetic riskPosttraumatic stress disorder symptomsAssociation studiesPheWASClinical comorbiditiesComorbid associationsEye conditionsAOUInverse relationshipMultiple phenotypesEffects of genetically predicted posttraumatic stress disorder on autoimmune phenotypes
Maihofer A, Ratanatharathorn A, Hemmings S, Costenbader K, Michopoulos V, Polimanti R, Rothbaum A, Seedat S, Mikita E, Smith A, Salem R, Shaffer R, Wu T, Sebat J, Ressler K, Stein M, Koenen K, Wolf E, Sumner J, Nievergelt C. Effects of genetically predicted posttraumatic stress disorder on autoimmune phenotypes. Translational Psychiatry 2024, 14: 172. PMID: 38561342, PMCID: PMC10984931, DOI: 10.1038/s41398-024-02869-0.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderMendelian randomizationTwo-sample Mendelian randomizationLinkage disequilibrium score regressionGenome-wide significant single nucleotide polymorphismsCorrelated horizontal pleiotropyGenetic architectures of phenotypesMultivariable MR analysisSignificant single nucleotide polymorphismsAssociation of posttraumatic stress disorderCausal effectsSingle nucleotide polymorphismsGenetic correlationsMR-PRESSOHorizontal pleiotropyStress disorderMR analysisScore regressionGenetic architectureC-reactive proteinInverse varianceMR estimatesNucleotide polymorphismsPathway variablesEpidemiological evidenceClinical spectrum of Transthyretin amyloidogenic mutations among diverse population origins
De Lillo A, Pathak G, Low A, De Angelis F, Abou Alaiwi S, Miller E, Fuciarelli M, Polimanti R. Clinical spectrum of Transthyretin amyloidogenic mutations among diverse population origins. Human Genomics 2024, 18: 31. PMID: 38523305, PMCID: PMC10962184, DOI: 10.1186/s40246-024-00596-7.Peer-Reviewed Original ResearchConceptsCardiac congenital anomaliesAmyloidogenic mutationsCross-ancestry meta-analysisCongenital anomaliesComplex genotype-phenotype correlationsVal122Ile mutationGenotype-phenotype correlationPeripheral nerve disordersHereditary form of amyloidosisAncestry-specificCross-ancestryEuropean-descent individualsEast AsiansTTR-related amyloidosisIndividuals of African descentPopulation originClinical presentationAtrioventricular blockClinical spectrumDelayed diagnosisTTR mutationsAfrican descentNerve disordersTransthyretin mutationMutationsSex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation
He J, Cabrera-Mendoza B, De Angelis F, Pathak G, Koller D, Curhan S, Curhan G, Mecca A, van Dyck C, Polimanti R. Sex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation. Brain 2024, 147: 3395-3408. PMID: 38454550, PMCID: PMC11449129, DOI: 10.1093/brain/awae077.Peer-Reviewed Original ResearchImaging-derived phenotypesHearing difficultiesBrain imaging-derived phenotypesSex-combined analysisLatent causal variable analysesMendelian randomization approachGeneralized linear regression analysisLocal genetic correlation analysisMultivariate generalized linear regression analysisGenome-wide association studiesLatent causal variableGenetic correlation analysisGenetic correlationsLocal genetic correlationMendelian randomizationPeripheral auditory systemOlder adultsGWAS dataLinear regression analysisHealth burdenGenomic regionsAssociation studiesPleiotropic regionsSex differencesTranscriptome regulationEstimating 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, PMCID: PMC11250798, 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 SAUnraveling COVID-19 relationship with anxiety disorders and symptoms using genome-wide data
Asgel Z, Kouakou M, Koller D, Pathak G, Cabrera-Mendoza B, Polimanti R. Unraveling COVID-19 relationship with anxiety disorders and symptoms using genome-wide data. Journal Of Affective Disorders 2024, 352: 333-341. PMID: 38382819, PMCID: PMC10939738, DOI: 10.1016/j.jad.2024.02.061.Peer-Reviewed Original ResearchAnxiety disordersAnxiety symptomsAnxiety outcomesPeriods of anxietyCorrelates of anxiety disordersGenome-wide dataLocal genetic correlationLatent causal variable analysesBrain morphologyAnxietyGenetic correlationsCOVID-19 positive statusGenetic causality proportionDisordersPleiotropic mechanismsMillion Veteran ProgramVeteran ProgramSymptomsCOVID-19 hospitalizationCOVID-19 Host Genetics InitiativeComorbidityMultiple lociHost Genetics InitiativeCOVID-19 outcomesPositive statusThe impact of assortative mating, participation bias and socioeconomic status on the polygenic risk of behavioural and psychiatric traits
Cabrera-Mendoza B, Wendt F, Pathak G, Yengo L, Polimanti R. The impact of assortative mating, participation bias and socioeconomic status on the polygenic risk of behavioural and psychiatric traits. Nature Human Behaviour 2024, 8: 976-987. PMID: 38366106, PMCID: PMC11161911, DOI: 10.1038/s41562-024-01828-5.Peer-Reviewed Original ResearchSocioeconomic statusParticipation biasPsychiatric traitsPolygenic riskFrequency of drinking alcoholDepressive disorderTourette syndromeImpact of assortative matingAlcohol-related traitsAlcohol use disorderAlcohol-related phenotypesInvestigate assortative matingSocioeconomic status conditionsHabitual alcohol intakeAssortative matingAlcohol intakeDrinking alcoholBipolar disorderQuestionnaire respondentsUse disorderMeta-analysisParticipantsGametic phase disequilibriumDisordersTourettePleiotropy and genetically inferred causality linking multisite chronic pain to substance use disorders
Koller D, Friligkou E, Stiltner B, Pathak G, Løkhammer S, Levey D, Zhou H, Hatoum A, Deak J, Kember R, Treur J, Kranzler H, Johnson E, Stein M, Gelernter J, Polimanti R. Pleiotropy and genetically inferred causality linking multisite chronic pain to substance use disorders. Molecular Psychiatry 2024, 29: 2021-2030. PMID: 38355787, PMCID: PMC11324857, DOI: 10.1038/s41380-024-02446-3.Peer-Reviewed Original ResearchMultisite chronic painSubstance use disordersChronic painUK BiobankUse disorderMillion Veteran ProgramSNP-based heritabilityGenome-wide association statisticsMR analysisPotential causal relationshipVeteran ProgramPleiotropy analysisTobacco usePleiotropic variantsOpioid use disorderAssociation statisticsCannabis use disorderAlcohol use disorderMeta-analysesBrain-wide analysisImaging phenotypesBi-directional relationshipPainPleiotropyBiobankGenetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders
Koller D, Mitjans M, Kouakou M, Friligkou E, Cabrera-Mendoza B, Deak J, Llonga N, Pathak G, Stiltner B, Løkhammer S, Levey D, Zhou H, Hatoum A, Kember R, Kranzler H, Stein M, Corominas R, Demontis D, Artigas M, Ramos-Quiroga J, Gelernter J, Ribasés M, Cormand B, Polimanti R. Genetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders. Psychiatry Research 2024, 333: 115758. PMID: 38335780, PMCID: PMC11157987, DOI: 10.1016/j.psychres.2024.115758.Peer-Reviewed Original ResearchConceptsUse disorderGenome-wide association studiesGenomic structural equation modelingCannabis use disorderAlcohol Use Disorders Identification TestAttention-deficit/hyperactivity disorderAlcohol use disorderProblematic alcohol useSubstance use disordersTwo-sample Mendelian randomization analysisLinkage disequilibrium score regression analysisDisorders Identification TestMendelian randomization analysisAssociated with increased oddsOdds of ADHDOpioid use disorderAttention-deficit/hyperactivityGWAS meta-analysesAlcohol dependenceStructural equation modelingNicotine dependenceInvestigate genetic correlationsADHDPolygenic riskStrength of evidenceFunctional correlates of a novel 8-factor model of PTSD in U.S. military veterans: Results from the National Health and Resilience in Veterans Study
Stiltner B, Fischer I, Duek O, Polimanti R, Harpaz-Rotem I, Pietrzak R. Functional correlates of a novel 8-factor model of PTSD in U.S. military veterans: Results from the National Health and Resilience in Veterans Study. Journal Of Psychiatric Research 2024, 171: 69-74. PMID: 38244335, DOI: 10.1016/j.jpsychires.2024.01.017.Peer-Reviewed Original ResearchConceptsModels of posttraumatic stress disorderPosttraumatic stress disorderNational Health and ResilienceU.S. military veteransArousal symptomsSuicidal ideationVeterans StudyCurrent depressionSymptom clustersMilitary veteransPosttraumatic stress disorder symptom clustersPosttraumatic stress disorder symptomsPosttraumatic Stress Disorder ChecklistAnxious arousal symptomsDysphoric arousal symptomsIntrusive symptom clustersOdds of suicidal ideationFunctional correlatesMulti-faceted disorderExternalizing behavioral symptomsAssociated with lower oddsAssociated with higher oddsSymptom structureAvoidance symptomsDSM-5Correction: Psychosocial moderators of polygenic risk scores of inflammatory biomarkers in relation to GrimAge
Tamman A, Koller D, Nagamatsu S, Cabrera-Mendoza B, Abdallah C, Krystal J, Gelernter J, Montalvo-Ortiz J, Polimanti R, Pietrzak R. Correction: Psychosocial moderators of polygenic risk scores of inflammatory biomarkers in relation to GrimAge. Neuropsychopharmacology 2024, 49: 764-764. PMID: 38182778, PMCID: PMC10876612, DOI: 10.1038/s41386-023-01786-y.Peer-Reviewed Original ResearchMulti-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference
Meng X, Navoly G, Giannakopoulou O, Levey D, Koller D, Pathak G, Koen N, Lin K, Adams M, Rentería M, Feng Y, Gaziano J, Stein D, Zar H, Campbell M, van Heel D, Trivedi B, Finer S, McQuillin A, Bass N, Chundru V, Martin H, Huang Q, Valkovskaya M, Chu C, Kanjira S, Kuo P, Chen H, Tsai S, Liu Y, Kendler K, Peterson R, Cai N, Fang Y, Sen S, Scott L, Burmeister M, Loos R, Preuss M, Actkins K, Davis L, Uddin M, Wani A, Wildman D, Aiello A, Ursano R, Kessler R, Kanai M, Okada Y, Sakaue S, Rabinowitz J, Maher B, Uhl G, Eaton W, Cruz-Fuentes C, Martinez-Levy G, Campos A, Millwood I, Chen Z, Li L, Wassertheil-Smoller S, Jiang Y, Tian C, Martin N, Mitchell B, Byrne E, Awasthi S, Coleman J, Ripke S, Sofer T, Walters R, McIntosh A, Polimanti R, Dunn E, Stein M, Gelernter J, Lewis C, Kuchenbaecker K. Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference. Nature Genetics 2024, 56: 222-233. PMID: 38177345, PMCID: PMC10864182, DOI: 10.1038/s41588-023-01596-4.Peer-Reviewed Original ResearchGenetic 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