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 dataAssociation 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 problemsVeteransUnraveling 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 statusPleiotropy 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 relationshipPainPleiotropyBiobank
2023
Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications
Levey D, Galimberti M, Deak J, Wendt F, Bhattacharya A, Koller D, Harrington K, Quaden R, Johnson E, Gupta P, Biradar M, Lam M, Cooke M, Rajagopal V, Empke S, Zhou H, Nunez Y, Kranzler H, Edenberg H, Agrawal A, Smoller J, Lencz T, Hougaard D, Børglum A, Demontis D, Gaziano J, Gandal M, Polimanti R, Stein M, Gelernter J. Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications. Nature Genetics 2023, 55: 2094-2103. PMID: 37985822, PMCID: PMC10703690, DOI: 10.1038/s41588-023-01563-z.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphism-based heritabilityMulti-ancestry genome-wide association studyAssociation studiesMillion Veteran ProgramGenome-wide association studiesWide significant lociWide association studySignificant lociReference panelSmall populationDisease biologyAncestryAmerican ancestryHeritabilityVeteran ProgramNumerous medical comorbiditiesLung cancer riskRelationship analysisLociBiologyPublic health implicationsEast AsiansPublic health consequencesMedical comorbiditiesCigarette smokingGenome-wide association studies and cross-population meta-analyses investigating short and long sleep duration
Austin-Zimmerman I, Levey D, Giannakopoulou O, Deak J, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Concato J, Buysse D, Gaziano J, Gottlieb D, Polimanti R, Stein M, Bramon E, Gelernter J. Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration. Nature Communications 2023, 14: 6059. PMID: 37770476, PMCID: PMC10539313, DOI: 10.1038/s41467-023-41249-y.Peer-Reviewed Original ResearchConceptsAssociation studiesGenome-wide association studiesGenetic correlationsWide association studyLinkage disequilibrium scorePositive genetic correlationSleep traitsIndependent lociMillion Veteran ProgramTraitsAncestryUK BiobankVeteran ProgramMendelian randomisationLociHeritabilitySNPsPhenotypeEast AsiansSimilar patternCardiometabolic phenotypes
2022
A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program
Verma A, Tsao NL, Thomann LO, Ho YL, Iyengar SK, Luoh SW, Carr R, Crawford DC, Efird JT, Huffman JE, Hung A, Ivey KL, Levin MG, Lynch J, Natarajan P, Pyarajan S, Bick AG, Costa L, Genovese G, Hauger R, Madduri R, Pathak GA, Polimanti R, Voight B, Vujkovic M, Zekavat SM, Zhao H, Ritchie MD, Initiative V, Chang KM, Cho K, Casas JP, Tsao PS, Gaziano JM, O’Donnell C, Damrauer SM, Liao KP. A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program. PLOS Genetics 2022, 18: e1010113. PMID: 35482673, PMCID: PMC9049369, DOI: 10.1371/journal.pgen.1010113.Peer-Reviewed Original ResearchConceptsSevere COVID-19Million Veteran ProgramPhenome-wide association studyHost Genetics InitiativeGenetic architectureGenotype-phenotype dataAssociation studiesVeterans Affairs Million Veteran ProgramElectronic health record dataCOVID-19 severityHealth record dataCOVID-19Genetic variantsGenetics InitiativeABO locusPhenotypeVenous embolismCritical illnessDiseases codesMedical conditionsInternational ClassificationRecord dataStrong associationVeteran ProgramVariantsAPOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program
Hung AM, Shah SC, Bick AG, Yu Z, Chen HC, Hunt CM, Wendt F, Wilson O, Greevy RA, Chung CP, Suzuki A, Ho YL, Akwo E, Polimanti R, Zhou J, Reaven P, Tsao PS, Gaziano JM, Huffman JE, Joseph J, Luoh SW, Iyengar S, Chang KM, Casas JP, Matheny ME, O’Donnell C, Cho K, Tao R, Susztak K, Robinson-Cohen C, Tuteja S, Siew ED, Hung A, Wallbom A, Palacio A, Robey B, Jhala D, Fujii D, Cohen D, Boyko E, Jacono F, Villareal G, Garcon H, Gaziano J, Lichy J, Norton J, Beckham J, Whittle J, Huffman J, Moser J, Greco J, Walsh J, Harley J, Wells J, Klein J, Moorman J, Constans J, Fayad J, Casas J, Xu J, Liao K, Alexander K, Cho K, Hammer K, Oursler K, Mattocks K, Chang K, Dellitalia L, Hamner M, Whooley M, Murdoch M, Gaddy M, Godschalk M, Rauchman M, Huq M, Tandon N, Kosik N, Ratcliffe N, Okusaga O, Roussos P, Strollo P, Meyer P, Sriram P, Wilson P, Liang P, Tsao P, Balasubramanian P, Ramoni R, McArdle R, Hauger R, Servatius R, Smith R, Striker R, Mathew R, Gappy S, Pyarajan S, Gutierrez S, Gupta S, Aguayo S, Sharma S, Damrauer S, Kinlay S, Yeh S, Luoh S, Tuteja S, Mastorides S, Iyengar S, Bhushan S, Muralidhar S, Ahuja S, Liangpunsakul S, Assimes T, Morgan T, Stapley T, Sun Y, Ballas Z. APOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program. JAMA Internal Medicine 2022, 182: 386-395. PMID: 35089317, PMCID: PMC8980930, DOI: 10.1001/jamainternmed.2021.8538.Peer-Reviewed Original ResearchConceptsAcute kidney injuryNormal kidney functionHigh-risk groupAPOL1 risk variantsKidney functionAKI severityKidney injuryCohort studyMillion Veteran ProgramHigher oddsCOVID-19-associated acute kidney injuryRisk variantsMultivariable logistic regression analysisCOVID-19AKI risk factorsAKI severity stageRetrospective cohort studyAfrican ancestryApolipoprotein L1COVID-19 infectionCoronavirus disease 2019Logistic regression analysisHigh mortality rateVeteran ProgramAPOL1 kidney risk variantsGenetically regulated multi-omics study for symptom clusters of posttraumatic stress disorder highlights pleiotropy with hematologic and cardio-metabolic traits
Pathak GA, Singh K, Wendt FR, Fleming TW, Overstreet C, Koller D, Tylee DS, De Angelis F, Cabrera Mendoza B, Levey DF, Koenen KC, Krystal JH, Pietrzak RH, O’ Donell C, Gaziano JM, Falcone G, Stein MB, Gelernter J, Pasaniuc B, Mancuso N, Davis LK, Polimanti R. Genetically regulated multi-omics study for symptom clusters of posttraumatic stress disorder highlights pleiotropy with hematologic and cardio-metabolic traits. Molecular Psychiatry 2022, 27: 1394-1404. PMID: 35241783, PMCID: PMC9210390, DOI: 10.1038/s41380-022-01488-9.Peer-Reviewed Original ResearchConceptsLocal genetic correlationsCell type-specific expressionVanderbilt University biorepositoryMulti-omics studiesMulti-omics investigationsDorsolateral prefrontal cortex tissueGenomic evidenceLaboratory traitsSpecific expressionCardio-metabolic traitsMillion Veteran ProgramPrefrontal cortex tissueMiR-148GenesGenetic correlationsRegulatory profileTraitsProtein expressionCardiometabolic traitsExpressionVeteran ProgramCortex tissueBiological heterogeneitySplicingPrioritization approach
2021
Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions
Levey DF, Stein MB, Wendt FR, Pathak GA, Zhou H, Aslan M, Quaden R, Harrington KM, Nuñez YZ, Overstreet C, Radhakrishnan K, Sanacora G, McIntosh AM, Shi J, Shringarpure SS, Concato J, Polimanti R, Gelernter J. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nature Neuroscience 2021, 24: 954-963. PMID: 34045744, PMCID: PMC8404304, DOI: 10.1038/s41593-021-00860-2.Peer-Reviewed Original ResearchConceptsTranscriptome-wide association studyMillion Veteran ProgramTranscriptome-wide association study (TWAS) analysisGenomic risk lociComplex psychiatric traitsGenetic architectureRisk lociGene expressionAssociation studiesLikely pathogenicityPsychiatric traitsVeteran ProgramNew therapeutic directionEuropean ancestryNew insightsAncestryUK BiobankAfrican ancestrySubstantial replicationExpressionLarge independent cohortsGWASTherapeutic directionsGenesLoci
2020
Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program
Levey DF, Gelernter J, Polimanti R, Zhou H, Cheng Z, Aslan M, Quaden R, Concato J, Radhakrishnan K, Bryois J, Sullivan PF, Stein M. Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program. American Journal Of Psychiatry 2020, 177: 223-232. PMID: 31906708, PMCID: PMC7869502, DOI: 10.1176/appi.ajp.2019.19030256.Peer-Reviewed Original ResearchConceptsNovel genome-wide significant associationsGene expressionGenome-wide significant signalsGenome-wide significant associationMillion Veteran ProgramWide association studyGenetic risk lociSignificant genetic correlationsGenetic risk mechanismsGenetic architectureGlobal regulatorChromosome 3Risk lociChromosome 6Chromosome 7Association studiesLargest GWASLarge biobanksGlobal regulationGenetic correlationsContinuous traitsVeteran ProgramGWASsLociPrevious GWASs
2019
Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans
Gelernter J, Sun N, Polimanti R, Pietrzak R, Levey DF, Bryois J, Lu Q, Hu Y, Li B, Radhakrishnan K, Aslan M, Cheung KH, Li Y, Rajeevan N, Sayward F, Harrington K, Chen Q, Cho K, Pyarajan S, Sullivan PF, Quaden R, Shi Y, Hunter-Zinck H, Gaziano JM, Concato J, Zhao H, Stein MB. Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans. Nature Neuroscience 2019, 22: 1394-1401. PMID: 31358989, PMCID: PMC6953633, DOI: 10.1038/s41593-019-0447-7.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHigh linkage disequilibrium regionLinkage disequilibrium regionWide association studyDisequilibrium regionBioinformatics analysisTranscriptomic profilesMillion Veteran ProgramChromosome 17Genetic risk factorsNew insightsUK Biobank dataReexperiencing of traumaStriatal medium spiny neuronsVeteran ProgramSignificant regionsCAMKVEuropean AmericansBiobank dataMedium spiny neuronsTCF4BiologyKANSL1African American cohort