2024
Genetically 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 disorderPleiotropy 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 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
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
2022
Phenome-wide association study of loci harboring de novo tandem repeat mutations in UK Biobank exomes
Wendt F, Pathak G, Polimanti R. Phenome-wide association study of loci harboring de novo tandem repeat mutations in UK Biobank exomes. Nature Communications 2022, 13: 7682. PMID: 36509785, PMCID: PMC9744822, DOI: 10.1038/s41467-022-35423-x.Peer-Reviewed Original ResearchConceptsProtein structureTandem repeatsTandem repeat mutationsPhenome-wide association studyAlters protein structureGenetic variationAssociation studiesEuropean ancestry participantsUK BiobankCarotid intima-media thicknessTR mutationsIntima-media thicknessMicroRNA-184Repeat mutationsFamily-based designsTestable hypothesesLociPopulation levelRespiratory outcomesMutationsDisease outcomeFAN1FNBP4RepeatsDenisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations
Koller D, Wendt F, Pathak G, De Lillo A, De Angelis F, Cabrera-Mendoza B, Tucci S, Polimanti R. Denisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations. BMC Biology 2022, 20: 249. PMID: 36344982, PMCID: PMC9641937, DOI: 10.1186/s12915-022-01449-2.Peer-Reviewed Original ResearchConceptsArchaic introgressionComplex traitsDenisovan introgressionNeanderthal allelesNeanderthal introgressionSignatures of admixtureAncestry groupsModern populationsPhenome-wide association studyModern human populationsMajor histocompatibility complex regionIntrogressionEvolutionary pressureGenetic poolDisease heritabilityGenomic signaturesEAS populationsExtinct NeanderthalsAssociation studiesMetabolic traitsDenisovansUK BiobankRed hair colorEuropean descentHuman traitsUnderstanding 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 disorderUsing 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
Biobank Scale Pharmacogenomics Informs the Genetic Underpinnings of Simvastatin Use
Wendt FR, Koller D, Pathak GA, Jacoby D, Miller EJ, Polimanti R. Biobank Scale Pharmacogenomics Informs the Genetic Underpinnings of Simvastatin Use. Clinical Pharmacology & Therapeutics 2021, 110: 777-785. PMID: 33837531, PMCID: PMC8376807, DOI: 10.1002/cpt.2260.Peer-Reviewed Original ResearchConceptsLDL-C concentrationsSimvastatin useLow-density lipoprotein cholesterol concentrationsLipoprotein cholesterol concentrationsDrug-metabolizing enzymesElectronic medical recordsStatin therapyStatin treatmentActivity scoreMedical recordsPilot cohortCholesterol concentrationsEuropean ancestry participantsMetabolizer phenotypeClinical decisionNAT2 allelesPolygenic riskNAT2Good responseUK BiobankBiological mechanismsPharmacogenesAssociationPotential benefitsPhenotypeCross-ancestry genome-wide association studies identified heterogeneous loci associated with differences of allele frequency and regulome tagging between participants of European descent and other ancestry groups from the UK Biobank
De Lillo A, D'Antona S, Pathak GA, Wendt FR, De Angelis F, Fuciarelli M, Polimanti R. Cross-ancestry genome-wide association studies identified heterogeneous loci associated with differences of allele frequency and regulome tagging between participants of European descent and other ancestry groups from the UK Biobank. Human Molecular Genetics 2021, 30: 1457-1467. PMID: 33890984, PMCID: PMC8283210, DOI: 10.1093/hmg/ddab114.Peer-Reviewed Original ResearchConceptsGWS associationsHeterogeneous lociGenome-wide association studiesEuropean populationsAncestry-specific effectsAllele frequenciesWide significant associationsPhenome-wide analysisAncestry groupsComplex traitsLD variationPhenotypic classesAssociation studiesUK BiobankMapping variantsLociConcordant effectsCentral/South AsianAncestryWorldwide populationTraitsAsian ancestryDiscordant effectsSouth Asian ancestryEuropean descent
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