2023
STRESS IN A DISH: MODELING THE IMPACT OF COMMON GENETIC VARIATION ON STRESS RESPONSE IN HIPSC-DERIVED NEURONS IN PTSD
Seah C, Signer R, Young H, Kozik E, Rusielewicz T, Bader H, Xu C, de Pins A, Breen M, Paull D, Yehuda R, Girgenti M, Brennand K, Huckins L. STRESS IN A DISH: MODELING THE IMPACT OF COMMON GENETIC VARIATION ON STRESS RESPONSE IN HIPSC-DERIVED NEURONS IN PTSD. European Neuropsychopharmacology 2023, 75: s40. DOI: 10.1016/j.euroneuro.2023.08.081.Peer-Reviewed Original ResearchCommon genetic variationGenetic variationStress responseCell typesEQTL associationsTranscriptional stress responseGenomic risk lociTissue-specific mannerChIP-seq datasetsCell type deconvolutionCommon genetic variantsPost-mortem brainsGene expression signaturesHiPSC-derived neuronsTranscription factorsSuch lociCatalog genesRisk lociGenetic studiesExpression signaturesGenetic variantsRegulatory activityGenesEQTLsMechanistic understandingT65. GENES IN POSTMORTEM BRAIN TISSUE DIFFERENTIALLY EXPRESSED IN CHRONIC PAIN
Collier L, Seah C, Kozik E, Group T, Girgenti M, Huckins L, Johnston K. T65. GENES IN POSTMORTEM BRAIN TISSUE DIFFERENTIALLY EXPRESSED IN CHRONIC PAIN. European Neuropsychopharmacology 2023, 75: s196-s197. DOI: 10.1016/j.euroneuro.2023.08.350.Peer-Reviewed Original ResearchChronic painBackground Chronic painBone cancer painPain-related conditionsVEGF BFalse discovery rate correctionCancer painEndometrial cancerRheumatoid arthritisBrain gene expression datasetsGene expressionPainPsychiatric conditionsLinear regression modelsMultiple testingSpecific cell typesGene expression analysisCell typesRate correctionRegression modelsSurrogate variablesDifferential gene expression analysisDACCMeasured variablesExpressionLeveraging base-pair mammalian constraint to understand genetic variation and human disease
Sullivan P, Meadows J, Gazal S, Phan B, Li X, Genereux D, Dong M, Bianchi M, Andrews G, Sakthikumar S, Nordin J, Roy A, Christmas M, Marinescu V, Wang C, Wallerman O, Xue J, Yao S, Sun Q, Szatkiewicz J, Wen J, Huckins L, Lawler A, Keough K, Zheng Z, Zeng J, Wray N, Li Y, Johnson J, Chen J, Paten B, Reilly S, Hughes G, Weng Z, Pollard K, Pfenning A, Forsberg-Nilsson K, Karlsson E, Lindblad-Toh K, Andrews G, Armstrong J, Bianchi M, Birren B, Bredemeyer K, Breit A, Christmas M, Clawson H, Damas J, Di Palma F, Diekhans M, Dong M, Eizirik E, Fan K, Fanter C, Foley N, Forsberg-Nilsson K, Garcia C, Gatesy J, Gazal S, Genereux D, Goodman L, Grimshaw J, Halsey M, Harris A, Hickey G, Hiller M, Hindle A, Hubley R, Hughes G, Johnson J, Juan D, Kaplow I, Karlsson E, Keough K, Kirilenko B, Koepfli K, Korstian J, Kowalczyk A, Kozyrev S, Lawler A, Lawless C, Lehmann T, Levesque D, Lewin H, Li X, Lind A, Lindblad-Toh K, Mackay-Smith A, Marinescu V, Marques-Bonet T, Mason V, Meadows J, Meyer W, Moore J, Moreira L, Moreno-Santillan D, Morrill K, Muntané G, Murphy W, Navarro A, Nweeia M, Ortmann S, Osmanski A, Paten B, Paulat N, Pfenning A, Phan B, Pollard K, Pratt H, Ray D, Reilly S, Rosen J, Ruf I, Ryan L, Ryder O, Sabeti P, Schäffer D, Serres A, Shapiro B, Smit A, Springer M, Srinivasan C, Steiner C, Storer J, Sullivan K, Sullivan P, Sundström E, Supple M, Swofford R, Talbot J, Teeling E, Turner-Maier J, Valenzuela A, Wagner F, Wallerman O, Wang C, Wang J, Weng Z, Wilder A, Wirthlin M, Xue J, Zhang X. Leveraging base-pair mammalian constraint to understand genetic variation and human disease. Science 2023, 380: eabn2937. PMID: 37104612, PMCID: PMC10259825, DOI: 10.1126/science.abn2937.Peer-Reviewed Original ResearchConceptsHuman genomeHuman diseasesCopy-number variationsHeritable human diseasesGenome annotationVariant annotationGenomic positionsGenomic regionsDisease heritabilityFunctional annotationEvolutionary constraintsAssociation studiesCopy-numberGenetic variationGenetic findingsGenomeCell typesRegulatory landscapeDisease mechanismsAnnotationBiological mechanismsCancer dataMammalsPredictor of functionHeritability
2022
Stem Cell Models for Context-Specific Modeling in Psychiatric Disorders
Seah C, Huckins L, Brennand K. Stem Cell Models for Context-Specific Modeling in Psychiatric Disorders. Biological Psychiatry 2022, 93: 642-650. PMID: 36658083, DOI: 10.1016/j.biopsych.2022.09.033.Peer-Reviewed Original ResearchConceptsStem cell modelCell typesTarget genesGenome-wide association study (GWAS) lociExpression quantitative trait lociGenome-wide association studiesParallel reporter assaysQuantitative trait lociStem cell-derived cell typesPluripotent stem cell modelsComplex polygenic architectureContext-specific mannerPsychiatric disorder riskTrait lociRegulates transcriptionStudy lociGenetic regulationPolygenic architectureCRISPR screensCell modelCausal variantsRegulated expressionPatient-specific humanReporter assaysAssociation studies