2022
Understanding 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 ResearchMeSH KeywordsComorbidityCoronary Artery DiseaseElectronic Health RecordsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideRisk FactorsStress Disorders, Post-TraumaticConceptsCoronary 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 disorderAn 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 ResearchMeSH KeywordsAsthmaColitis, UlcerativeCrohn DiseaseGenome-Wide Association StudyHumansPhenotypePolymorphism, Single NucleotideRhinitis, AllergicConceptsRisk 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 studiesColitisAsthmaUnderstanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation: discovering causal pathways
Kasher M, Williams F, Freidin M, Malkin I, Cherny S, Benjamin E, Chasman D, Dehghan A, Ahluwalia T, Meigs J, Tracy R, Alizadeh B, Ligthart S, Bis J, Eiriksdottir G, Pankratz N, Gross M, Rainer A, Snieder H, Wilson J, Psaty B, Dupuis J, Prins B, Vaso U, Stathopoulou M, Franke L, Lehtimaki T, Koenig W, Jamshidi Y, Siest S, Abbasi A, Uitterlinden A, Abdollahi M, Schnabel R, Schick U, Nolte I, Kraja A, Hsu Y, Tylee D, Zwicker A, Uher R, Davey-Smith G, Morrison A, Hicks A, van Duijn C, Ward-Caviness C, Boerwinkle E, Rotter J, Rice K, Lange L, Perola M, de Geus E, Morris A, Makela K, Stacey D, Eriksson J, Frayling T, Slagboom E, Livshits G. Understanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation: discovering causal pathways. Human Molecular Genetics 2022, 31: 2623-2632. PMID: 35349660, PMCID: PMC9402243, DOI: 10.1093/hmg/ddac061.Peer-Reviewed Original ResearchMeSH KeywordsArthritis, RheumatoidC-Reactive ProteinGenome-Wide Association StudyHumansInflammationMendelian Randomization AnalysisOsteoporosisPolymorphism, Single NucleotideConceptsCausal single nucleotide polymorphismsSingle nucleotide polymorphismsGenetic architectureColocalization analysisSame molecular functionAnalysis of pleiotropyComplex genetic architectureGenome-wide association study summary statisticsOp phenotypeMolecular functionsGenomic regionsPleiotropyOsteoporosis ConsortiumGenetic relationshipsGenetic backgroundGenetic variantsNucleotide polymorphismsMendelian randomizationGenesTraitsPhenotypeGenetic factorsProtein bindingUK BiobankHorizontal pleiotropy
2020
Characterizing the effect of background selection on the polygenicity of brain-related traits
Wendt FR, Pathak GA, Overstreet C, Tylee DS, Gelernter J, Atkinson EG, Polimanti R. Characterizing the effect of background selection on the polygenicity of brain-related traits. Genomics 2020, 113: 111-119. PMID: 33278486, PMCID: PMC7855394, DOI: 10.1016/j.ygeno.2020.11.032.Peer-Reviewed Original ResearchMeSH KeywordsBrainGenetic BackgroundGenetic HeterogeneityHumansMental DisordersMultifactorial InheritancePhenotypePolymorphism, Single NucleotideSelection, GeneticConceptsGenome-wide association studiesBrain-related traitsGWAS of schizophreniaTrait-associated lociLocus effect sizesSubset of traitsGenotype networksGenetic architectureIntolerant regionsBrain-related phenotypesBackground selectionNatural selectionEvolutionary pressurePositive selectionSNP heritabilityLocal ancestryAssociation studiesTraitsFunctional significanceLociPolygenicityBinary annotationPhenotypeRisk allelesSize variance
2019
A polygenic resilience score moderates the genetic risk for schizophrenia
Hess JL, Tylee DS, Mattheisen M, Børglum A, Als T, Grove J, Werge T, Mortensen P, Mors O, Nordentoft M, Hougaard D, Byberg-Grauholm J, Bækvad-Hansen M, Greenwood T, Tsuang M, Curtis D, Steinberg S, Sigurdsson E, Stefánsson H, Stefánsson K, Edenberg H, Holmans P, Faraone S, Glatt S. A polygenic resilience score moderates the genetic risk for schizophrenia. Molecular Psychiatry 2019, 26: 800-815. PMID: 31492941, PMCID: PMC7058518, DOI: 10.1038/s41380-019-0463-8.Peer-Reviewed Original Research
2018
Genetic correlations among psychiatric and immune‐related phenotypes based on genome‐wide association data
Tylee DS, Sun J, Hess JL, Tahir MA, Sharma E, Malik R, Worrall BB, Levine AJ, Martinson JJ, Nejentsev S, Speed D, Fischer A, Mick E, Walker BR, Crawford A, Grant SFA, Polychronakos C, Bradfield JP, Sleiman PMA, Hakonarson H, Ellinghaus E, Elder JT, Tsoi LC, Trembath RC, Barker JN, Franke A, Dehghan A, Team T, Consortium T, Consortium T, Registry T, Group T, Consortium T, Faraone SV, Glatt SJ. Genetic correlations among psychiatric and immune‐related phenotypes based on genome‐wide association data. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2018, 177: 641-657. PMID: 30325587, PMCID: PMC6230304, DOI: 10.1002/ajmg.b.32652.Peer-Reviewed Original ResearchConceptsImmune-related phenotypesPsychiatric disordersSystemic lupus erythematosusPrimary biliary cirrhosisLinkage disequilibrium score regressionImmune-related disordersAttention deficit hyperactivity disorderAutoimmune comorbiditiesDeficit hyperactivity disorderLupus erythematosusUlcerative colitisBiliary cirrhosisCrohn's diseaseObsessive-compulsive disorderMajor depressionImmunological stateSmoking behaviorTourette syndromeBipolar disorderAnorexia nervosaSummary-level dataEpidemiological literatureImmune signalingRespective disordersDisorders