2023
A statistical framework to identify cell types whose genetically regulated proportions are associated with complex diseases
Liu W, Deng W, Chen M, Dong Z, Zhu B, Yu Z, Tang D, Sauler M, Lin C, Wain L, Cho M, Kaminski N, Zhao H. A statistical framework to identify cell types whose genetically regulated proportions are associated with complex diseases. PLOS Genetics 2023, 19: e1010825. PMID: 37523391, PMCID: PMC10414598, DOI: 10.1371/journal.pgen.1010825.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsFemaleGene Expression ProfilingGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLungPolymorphism, Single NucleotidePulmonary Disease, Chronic ObstructiveConceptsCell typesDisease-associated tissuesWide association studyComplex diseasesCell type proportionsDisease-relevant tissuesReal GWAS dataFunctional genesTranscriptomic dataGWAS dataGenetic dataAssociation studiesNovel statistical frameworkChronic obstructive pulmonary diseaseStatistical frameworkObstructive pulmonary diseaseIdiopathic pulmonary fibrosisBreast cancer riskType proportionsBlood CD8Pulmonary diseasePulmonary fibrosisPredictive biomarkersLung tissueBreast cancer
2022
Integrative analyses for the identification of idiopathic pulmonary fibrosis-associated genes and shared loci with other diseases
Chen M, Zhang Y, Adams T, Ji D, Jiang W, Wain LV, Cho M, Kaminski N, Zhao H. Integrative analyses for the identification of idiopathic pulmonary fibrosis-associated genes and shared loci with other diseases. Thorax 2022, 78: 792-798. PMID: 36216496, PMCID: PMC10083187, DOI: 10.1136/thorax-2021-217703.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIdiopathic Pulmonary FibrosisLungTranscription FactorsConceptsTranscriptome-wide association analysisLocal genetic correlationsSingle-cell expression dataCandidate genesTranscription factorsIntegrative analysisGenomic regionsGenetic correlationsExpression dataTF target genesComplex genetic architectureTF binding sitesWide association studyPower of GWASSpecific DEGsGenetic architectureNew genesNovel genesCausal genesTarget genesGenetic basisEnrichment analysisAssociation studiesRegulatory roleAssociation analysis
2020
Genetic determinants of ammonia-induced acute lung injury in mice
Bein K, Ganguly K, Martin TM, Concel VJ, Brant KA, Di YPP, Upadhyay S, Fabisiak JP, Vuga LJ, Kaminski N, Kostem E, Eskin E, Prows DR, Jang AS, Leikauf GD. Genetic determinants of ammonia-induced acute lung injury in mice. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2020, 320: l41-l62. PMID: 33050709, PMCID: PMC7847062, DOI: 10.1152/ajplung.00276.2020.Peer-Reviewed Original ResearchConceptsSNP associationsWide association mappingGenetic determinantsSignificant SNP associationsAcute lung injuryIntegrative functional approachAssociation mappingMolecular functionsTranscriptomic analysisCandidate genesFunctional domainsNonsynonymous SNPsPromoter regionLung injuryDiverse panelGenesSNPsMouse strainsPathophysiological roleAATFInjuryProteinLAMA3ExpressionAssemblyCOVID-19 vulnerability: the potential impact of genetic susceptibility and airborne transmission
Godri Pollitt KJ, Peccia J, Ko AI, Kaminski N, Dela Cruz CS, Nebert DW, Reichardt JKV, Thompson DC, Vasiliou V. COVID-19 vulnerability: the potential impact of genetic susceptibility and airborne transmission. Human Genomics 2020, 14: 17. PMID: 32398162, PMCID: PMC7214856, DOI: 10.1186/s40246-020-00267-3.Peer-Reviewed Original ResearchMeSH KeywordsAir MicrobiologyBetacoronavirusCoronavirus InfectionsCOVID-19Disease Transmission, InfectiousGenetic Predisposition to DiseaseHumansPandemicsPersonal Protective EquipmentPneumonia, ViralSARS-CoV-2Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis
Allen RJ, Guillen-Guio B, Oldham JM, Ma SF, Dressen A, Paynton ML, Kraven LM, Obeidat M, Li X, Ng M, Braybrooke R, Molina-Molina M, Hobbs BD, Putman RK, Sakornsakolpat P, Booth HL, Fahy WA, Hart SP, Hill MR, Hirani N, Hubbard RB, McAnulty RJ, Millar AB, Navaratnam V, Oballa E, Parfrey H, Saini G, Whyte MKB, Zhang Y, Kaminski N, Adegunsoye A, Strek ME, Neighbors M, Sheng XR, Gudmundsson G, Gudnason V, Hatabu H, Lederer DJ, Manichaikul A, Newell JD, O’Connor G, Ortega VE, Xu H, Fingerlin TE, Bossé Y, Hao K, Joubert P, Nickle DC, Sin DD, Timens W, Furniss D, Morris AP, Zondervan KT, Hall IP, Sayers I, Tobin MD, Maher TM, Cho MH, Hunninghake GM, Schwartz DA, Yaspan BL, Molyneaux PL, Flores C, Noth I, Jenkins RG, Wain LV. Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2020, 201: 564-574. PMID: 31710517, PMCID: PMC7047454, DOI: 10.1164/rccm.201905-1017oc.Peer-Reviewed Original ResearchMeSH KeywordsAgedCase-Control StudiesCell Cycle ProteinsFemaleGene ExpressionGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIdiopathic Pulmonary FibrosisIntracellular Signaling Peptides and ProteinsKinesinsMaleMiddle AgedRisk AssessmentSignal TransductionSpindle ApparatusTOR Serine-Threonine KinasesConceptsGenome-wide association studiesAssociation studiesIPF susceptibilityNew genome-wide significant signalsGenome-wide significant signalsGenome-wide analysisCell-cell adhesionLarge genome-wide association studiesImportance of mTORPolygenic risk score analysisTelomere maintenanceCausal genesFunctional analysisSusceptibility variantsRisk score analysisMultiple pathwaysGenetic associationGenesHost defensePolygenic risk scoresIndependent studiesPossible roleExpression associatesSignificant signalRecent studies
2018
Gene correlation network analysis to identify regulatory factors in idiopathic pulmonary fibrosis
McDonough JE, Kaminski N, Thienpont B, Hogg JC, Vanaudenaerde BM, Wuyts WA. Gene correlation network analysis to identify regulatory factors in idiopathic pulmonary fibrosis. Thorax 2018, 74: 132. PMID: 30366970, PMCID: PMC6467239, DOI: 10.1136/thoraxjnl-2018-211929.Peer-Reviewed Original ResearchMeSH KeywordsAgedFemaleGene Regulatory NetworksGenetic Predisposition to DiseaseHumansIdiopathic Pulmonary FibrosisLungMaleMiddle AgedReproducibility of ResultsRespiratory Function TestsSurvival AnalysisTranscriptomeConceptsIdiopathic pulmonary fibrosisLung functionPulmonary fibrosisExtensive pathological changesSevere lung diseaseLung Tissue Research ConsortiumCorrelation network analysisIPF cohortIPF groupLung diseaseControl subjectsUpregulated modulesT cellsImmune responsePathological changesLeucocyte activationB cellsClinical relevanceSurfactant metabolismDisease pathologyInterferon responseFibrosisBlood vesselsPathological processesGene correlation network analysis
2017
Extreme Trait Whole-Genome Sequencing Identifies PTPRO as a Novel Candidate Gene in Emphysema with Severe Airflow Obstruction
Radder JE, Zhang Y, Gregory AD, Yu S, Kelly NJ, Leader JK, Kaminski N, Sciurba FC, Shapiro SD. Extreme Trait Whole-Genome Sequencing Identifies PTPRO as a Novel Candidate Gene in Emphysema with Severe Airflow Obstruction. American Journal Of Respiratory And Critical Care Medicine 2017, 196: 159-171. PMID: 28199135, PMCID: PMC5519967, DOI: 10.1164/rccm.201606-1147oc.Peer-Reviewed Original ResearchConceptsNovel candidate genesCandidate genesSuggestive associationSuggestive candidate genesRare genetic variationRare variationRegion-based testsGene-based testsSingle-variant testsRare nonsynonymous variantsWhole-genome sequencingRare variantsWhole genome sequencing resultsGenomic regionsGenetic variationGenetic association studiesDisease heritabilityCellular pathwaysAssociation studiesExtreme phenotypesPTPRONonsynonymous variantsSequencing resultsGenesDisease susceptibility
2016
Expression of asthma susceptibility genes in bronchial epithelial cells and bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort
Li X, Hawkins GA, Moore WC, Hastie AT, Ampleford EJ, Milosevic J, Li H, Busse WW, Erzurum SC, Kaminski N, Wenzel SE, Bleecker ER, Meyers DA. Expression of asthma susceptibility genes in bronchial epithelial cells and bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort. Journal Of Asthma 2016, 53: 775-782. PMID: 27050946, PMCID: PMC5137190, DOI: 10.3109/02770903.2016.1158268.Peer-Reviewed Original ResearchGenome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia
Fingerlin TE, Zhang W, Yang IV, Ainsworth HC, Russell PH, Blumhagen RZ, Schwarz MI, Brown KK, Steele MP, Loyd JE, Cosgrove GP, Lynch DA, Groshong S, Collard HR, Wolters PJ, Bradford WZ, Kossen K, Seiwert SD, du Bois RM, Garcia CK, Devine MS, Gudmundsson G, Isaksson HJ, Kaminski N, Zhang Y, Gibson KF, Lancaster LH, Maher TM, Molyneaux PL, Wells AU, Moffatt MF, Selman M, Pardo A, Kim DS, Crapo JD, Make BJ, Regan EA, Walek DS, Daniel JJ, Kamatani Y, Zelenika D, Murphy E, Smith K, McKean D, Pedersen BS, Talbert J, Powers J, Markin CR, Beckman KB, Lathrop M, Freed B, Langefeld CD, Schwartz DA. Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia. BMC Genomic Data 2016, 17: 74. PMID: 27266705, PMCID: PMC4895966, DOI: 10.1186/s12863-016-0377-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedChromosomes, Human, Pair 6FemaleGene Expression ProfilingGene Expression RegulationGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHLA-DQ beta-ChainsHLA-DRB1 ChainsHumansIdiopathic Pulmonary FibrosisLinkage DisequilibriumMaleMiddle AgedPulmonary FibrosisSequence Analysis, RNAConceptsRisk lociGenome-wide single nucleotide polymorphism (SNP) dataGenome-wide significant associationSingle nucleotide polymorphism dataGenome-wide genotypesRNA sequencing studiesNucleotide polymorphism dataTargeted gene expressionIdiopathic interstitial pneumoniaHigh linkage disequilibriumLung tissueGene regulationHLA allelesRNA sequencingPolymorphism dataRisk allelesGene expressionChromosome 6Protein structureInterstitial pneumoniaHLA regionSequencing studiesGenetic risk allelesAssociation analysisReplication genotyping
2015
Solving the Conundrum: Immunogenetics of Sarcoidosis
Kaminski N, Drake WP. Solving the Conundrum: Immunogenetics of Sarcoidosis. American Journal Of Respiratory And Critical Care Medicine 2015, 192: 652-654. PMID: 26371809, PMCID: PMC4595685, DOI: 10.1164/rccm.201506-1235ed.Peer-Reviewed Original ResearchFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMalePolymorphism, Single NucleotideSarcoidosiseQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes
Li X, Hastie AT, Hawkins GA, Moore WC, Ampleford EJ, Milosevic J, Li H, Busse WW, Erzurum SC, Kaminski N, Wenzel SE, Meyers DA, Bleecker ER. eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes. Allergy 2015, 70: 1309-1318. PMID: 26119467, PMCID: PMC4583797, DOI: 10.1111/all.12683.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAsthmaBronchoalveolar Lavage FluidCase-Control StudiesChromosome MappingEpithelial CellsFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansImmunoglobulin EMaleOrgan SpecificityPolymorphism, Single NucleotideQuantitative Trait LociRespiratory Function TestsRespiratory MucosaConceptsExpression quantitative trait lociGenome-wide association studiesSingle nucleotide polymorphismsAsthma genesQuantitative trait lociGenes/single-nucleotide polymorphismsCis-eQTL analysisFurther functional studiesDisease-relevant tissuesDecreased expressionTrait lociCausal genesTranscription analysisGene expressionPromoter regionAsthma-related genesAssociation studiesBronchial epithelial cellsProtein secretionGenesFunctional studiesNucleotide polymorphismsSpecific regulationExpression levelsExpression of IL33
2014
Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report
Blackwell TS, Tager AM, Borok Z, Moore BB, Schwartz DA, Anstrom KJ, Bar-Joseph Z, Bitterman P, Blackburn MR, Bradford W, Brown KK, Chapman HA, Collard HR, Cosgrove GP, Deterding R, Doyle R, Flaherty KR, Garcia CK, Hagood JS, Henke CA, Herzog E, Hogaboam CM, Horowitz JC, King TE, Loyd JE, Lawson WE, Marsh CB, Noble PW, Noth I, Sheppard D, Olsson J, Ortiz LA, O’Riordan T, Oury TD, Raghu G, Roman J, Sime PJ, Sisson TH, Tschumperlin D, Violette SM, Weaver TE, Wells RG, White ES, Kaminski N, Martinez FJ, Wynn TA, Thannickal VJ, Eu JP. Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report. American Journal Of Respiratory And Critical Care Medicine 2014, 189: 214-222. PMID: 24160862, PMCID: PMC3983890, DOI: 10.1164/rccm.201306-1141ws.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsBiomedical ResearchDisease Models, AnimalExtracellular MatrixGenetic Predisposition to DiseaseHumansIdiopathic Pulmonary FibrosisInflammationMicePulmonary AlveoliRespiratory MucosaConceptsIdiopathic pulmonary fibrosisAlveolar epithelial injuryEffective medical therapyRole of inflammationTime of diagnosisPatient advocacy groupsMedian survivalMedical therapyEpithelial injuryPulmonary fibrosisPulmonary fibrosis researchIPF therapyIPF researchPreclinical modelingDrug AdministrationPatient communityU.S. FoodNHLBITranslation of discoveriesClinical researchersPatientsFibrosis researchTherapyDiseaseAberrant repair
2013
Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study
Noth I, Zhang Y, Ma SF, Flores C, Barber M, Huang Y, Broderick SM, Wade MS, Hysi P, Scuirba J, Richards TJ, Juan-Guardela BM, Vij R, Han MK, Martinez FJ, Kossen K, Seiwert SD, Christie JD, Nicolae D, Kaminski N, Garcia J. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. The Lancet Respiratory Medicine 2013, 1: 309-317. PMID: 24429156, PMCID: PMC3894577, DOI: 10.1016/s2213-2600(13)70045-6.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significanceSingle nucleotide polymorphismsAssociation studiesThree-stage genome-wide association studyDiscovery Genome-Wide Association StudiesGene expression profiling dataGenetic variantsWide association studyRare genetic variantsAdditional common variantsDNA samplesMinor alleleCommon single nucleotide polymorphismsNovel variantsPulmonary Fibrosis FoundationDatabase of GenotypesGenetic lociTollip expressionNucleotide polymorphismsProfiling dataSNP genotypesCommon variantsIPF susceptibilityCommon allelesGenome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis
Fingerlin TE, Murphy E, Zhang W, Peljto AL, Brown KK, Steele MP, Loyd JE, Cosgrove GP, Lynch D, Groshong S, Collard HR, Wolters PJ, Bradford WZ, Kossen K, Seiwert SD, du Bois RM, Garcia CK, Devine MS, Gudmundsson G, Isaksson HJ, Kaminski N, Zhang Y, Gibson KF, Lancaster LH, Cogan JD, Mason WR, Maher TM, Molyneaux PL, Wells AU, Moffatt MF, Selman M, Pardo A, Kim DS, Crapo JD, Make BJ, Regan EA, Walek DS, Daniel JJ, Kamatani Y, Zelenika D, Smith K, McKean D, Pedersen BS, Talbert J, Kidd RN, Markin CR, Beckman KB, Lathrop M, Schwarz MI, Schwartz DA. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nature Genetics 2013, 45: 613-620. PMID: 23583980, PMCID: PMC3677861, DOI: 10.1038/ng.2609.Peer-Reviewed Original Research
2012
Integrative Assessment of Chlorine-Induced Acute Lung Injury in Mice
Leikauf GD, Pope-Varsalona H, Concel VJ, Liu P, Bein K, Berndt A, Martin TM, Ganguly K, Jang AS, Brant KA, Dopico RA, Upadhyay S, Di YP, Li Q, Hu Z, Vuga LJ, Medvedovic M, Kaminski N, You M, Alexander DC, McDunn JE, Prows DR, Knoell DL, Fabisiak JP. Integrative Assessment of Chlorine-Induced Acute Lung Injury in Mice. American Journal Of Respiratory Cell And Molecular Biology 2012, 47: 234-244. PMID: 22447970, PMCID: PMC3423464, DOI: 10.1165/rcmb.2012-0026oc.Peer-Reviewed Original ResearchConceptsCandidate genesGenetic basisProtein catabolic processAcute lung injuryLung injuryHaplotype association mappingC57BLKS/JSingle nucleotide polymorphism associationsAssociation mappingMetabolomic profilingProtein transportCatabolic processTranscript levelsHaplotype mappingChromosome 1Chlorine-induced acute lung injuryAmino acid carrierSNP associationsReal-time PCRGenesGenetic associationMean survival timeRecognition sitesProfilingPromoter SNPsAllele-specific transactivation of matrix metalloproteinase 7 by FOXA2 and correlation with plasma levels in idiopathic pulmonary fibrosis
Richards TJ, Park C, Chen Y, Gibson KF, Di Y, Pardo A, Watkins SC, Choi AM, Selman M, Pilewski J, Kaminski N, Zhang Y. Allele-specific transactivation of matrix metalloproteinase 7 by FOXA2 and correlation with plasma levels in idiopathic pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2012, 302: l746-l754. PMID: 22268124, PMCID: PMC3331579, DOI: 10.1152/ajplung.00319.2011.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisMatrix metalloproteinase-7Plasma levelsIPF patientsPulmonary fibrosisMetalloproteinase-7MMP7 promoterIPF cohortIPF lungsPeripheral bloodHealthy controlsEmbryonic lung developmentPromoter polymorphismAA genotypeCT genotypeForkhead box A2 transcription factorMature lungLung developmentLungEpithelial cellsRs11568818PatientsFibrosisUpregulationKey regulator
2011
The HLA Class II Allele DRB1*1501 Is Over-Represented in Patients with Idiopathic Pulmonary Fibrosis
Xue J, Gochuico BR, Alawad AS, Feghali-Bostwick CA, Noth I, Nathan SD, Rosen GD, Rosas IO, Dacic S, Ocak I, Fuhrman CR, Cuenco KT, Smith MA, Jacobs SS, Zeevi A, Morel PA, Pilewski JM, Valentine VG, Gibson KF, Kaminski N, Sciurba FC, Zhang Y, Duncan SR. The HLA Class II Allele DRB1*1501 Is Over-Represented in Patients with Idiopathic Pulmonary Fibrosis. PLOS ONE 2011, 6: e14715. PMID: 21373184, PMCID: PMC3044131, DOI: 10.1371/journal.pone.0014715.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisIPF patientsIPF subjectsAmbulatory patientsPulmonary fibrosisLung diseaseHLA-DRB1Normal subjectsEtiology of IPFHuman leukocyte antigen (HLA) allele frequenciesManifestations of IPFAbnormal adaptive immune responsesLung transplantation recipientsHLA class IIAdaptive immune responsesU.S. medical centersHLA-DR locusNormal reference populationDistinct clinical phenotypesRefractory lung diseaseSpecific HLA-DRB1Lung transplantationTransplant recipientsTransplantation recipientsGrim prognosis
2010
Functional Genomics of Chlorine-induced Acute Lung Injury in Mice
Leikauf GD, Pope-Varsalona H, Concel VJ, Liu P, Bein K, Brant KA, Dopico RA, Di YP, Jang AS, Dietsch M, Medvedovic M, Li Q, Vuga LJ, Kaminski N, You M, Prows DR. Functional Genomics of Chlorine-induced Acute Lung Injury in Mice. Annals Of The American Thoracic Society 2010, 7: 294-296. PMID: 20601635, PMCID: PMC3136967, DOI: 10.1513/pats.201001-005sm.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChlorineFemaleGasesGenetic Predisposition to DiseaseGenomicsInhalation ExposureLungLung DiseasesMiceMice, Inbred StrainsModels, AnimalConceptsAcute lung injuryChlorine-induced acute lung injuryLung injuryMouse strainsMean survival timeGene-targeted miceSusceptibility candidate genesSupportive measuresSurvival timeDivergent strainsInjuryCandidate genesCritical candidate genesFunctional genomics approachMiceAdditional genetic analysesMolecular eventsFunctional significanceFunctional genomicsGenomic approachesChlorine exposureGenetic basisNovel insightsGenetic analysisHospitalization