Featured Publications
Sex 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 regulationGenetic 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 smokingAn Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes
Tylee DS, Lee YK, Wendt FR, Pathak GA, Levey DF, De Angelis F, Gelernter J, Polimanti R. An Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes. JAMA Psychiatry 2022, 79: 667-676. PMID: 35507366, PMCID: PMC9069342, DOI: 10.1001/jamapsychiatry.2022.0914.Peer-Reviewed Original ResearchConceptsRisk factorsImmune-related phenotypesMultivariable adjustmentUlcerative colitisCrohn's diseaseMendelian randomizationImmune-related disordersReciprocal risk factorsHealth-related behaviorsPsychiatric phenotypesFalse discovery rate correctionAllergic rhinitisGenetic association studiesGenetic associationInflammatory disordersClinical associationsMajor depressionImmune disordersMAIN OUTCOMEPsychiatric disordersSocial determinantsDisordersAssociation studiesColitisAsthma
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 dataGenetically 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 disorderEffects 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 evidenceEstimating 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 SA
2023
Brainwide Mendelian Randomization Study of Anxiety Disorders and Symptoms
Zanoaga M, Friligkou E, He J, Pathak G, Koller D, Cabrera-Mendoza B, Stein M, Polimanti R. Brainwide Mendelian Randomization Study of Anxiety Disorders and Symptoms. Biological Psychiatry 2023, 95: 810-817. PMID: 37967698, PMCID: PMC10978301, DOI: 10.1016/j.biopsych.2023.11.006.Peer-Reviewed Original ResearchImaging-derived phenotypesMiddle cingulate gyrusBrain imaging-derived phenotypesCingulate gyrusBrain structuresMultivariable Mendelian randomization analysesRight anterior superior temporal gyrusGray matter volumeMendelian randomizationAnterior superior temporal gyrusUK BiobankMendelian randomization studyFalse discovery rate correctionSuperior temporal gyrusMultivariable Mendelian randomizationMendelian randomization analysisMillion Veteran ProgramLarge cohortMatter volumeRandomization studySymptom-level analysesTemporal gyrusAnxiety disordersRandomization analysisGyrus
2020
Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits
Zhou H, Sealock JM, Sanchez-Roige S, Clarke TK, Levey DF, Cheng Z, Li B, Polimanti R, Kember RL, Smith RV, Thygesen JH, Morgan MY, Atkinson SR, Thursz MR, Nyegaard M, Mattheisen M, Børglum AD, Johnson EC, Justice AC, Palmer AA, McQuillin A, Davis LK, Edenberg HJ, Agrawal A, Kranzler HR, Gelernter J. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nature Neuroscience 2020, 23: 809-818. PMID: 32451486, PMCID: PMC7485556, DOI: 10.1038/s41593-020-0643-5.Peer-Reviewed Original ResearchConceptsRegulatory genomic regionsGenome-wide association studiesNovel risk lociEuropean ancestry individualsPolygenic risk score analysisIndependent risk variantsGenetic architectureGenomic regionsRisk lociAssociation studiesGenetic relationshipsRisk genesGenetic correlationsPsychiatric traitsRisk variantsRisk score analysisTraitsGenetic heritabilityYields insightsBiobank samplesMendelian randomizationGenesLociBiologyHeritability
2019
Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium
Polimanti R, Peterson RE, Ong JS, MacGregor S, Edwards AC, Clarke TK, Frank J, Gerring Z, Gillespie NA, Lind PA, Maes HH, Martin NG, Mbarek H, Medland SE, Streit F, Agrawal A, Edenberg H, Kendler K, Lewis C, Sullivan P, Wray N, Gelernter J, Derks E. Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium. Psychological Medicine 2019, 49: 1218-1226. PMID: 30929657, PMCID: PMC6565601, DOI: 10.1017/s0033291719000667.Peer-Reviewed Original ResearchConceptsMajor depressionAlcohol dependenceAlcohol consumptionPsychiatric Genomics ConsortiumImportant public health concernMendelian randomizationPublic health concernUK BiobankClinical associationsHealth concernMR analysisReverse causationCausal roleNon-significant resultsCausal relationshipGenetic liabilityGenomics ConsortiumLinkage disequilibrium score regressionIntervention efforts