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 cancerPCSK6 and Survival in Idiopathic Pulmonary Fibrosis
Oldham J, Allen R, Lorenzo-Salazar J, Molyneaux P, Ma S, Joseph C, Kim J, Guillen-Guio B, Hernández-Beeftink T, Kropski J, Huang Y, Lee C, Adegunsoye A, Pugashetti J, Linderholm A, Vo V, Strek M, Jou J, Muñoz-Barrera A, Rubio-Rodriguez L, Hubbard R, Hirani N, Whyte M, Hart S, Nicholson A, Lancaster L, Parfrey H, Rassl D, Wallace W, Valenzi E, Zhang Y, Mychaleckyj J, Stockwell A, Kaminski N, Wolters P, Molina-Molina M, Banovich N, Fahy W, Martinez F, Hall I, Tobin M, Maher T, Blackwell T, Yaspan B, Jenkins R, Flores C, Wain L, Noth I. PCSK6 and Survival in Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2023, 207: 1515-1524. PMID: 36780644, PMCID: PMC10263132, DOI: 10.1164/rccm.202205-0845oc.Peer-Reviewed Original ResearchMeSH KeywordsEuropeGenome-Wide Association StudyHumansIdiopathic Pulmonary FibrosisLungProportional Hazards ModelsProprotein ConvertasesSerine EndopeptidasesConceptsGenome-wide significanceTransplantation-free survivalIdiopathic pulmonary fibrosisStage IIPF survivalDownstream analysisPulmonary fibrosisIPF progressionWide association studyPeripheral blood gene expressionProportional hazards regressionStage II casesLimited treatment optionsStage I casesBlood gene expressionGene expressionAssociation studiesMolecular determinantsHazards regressionTreatment optionsPlasma concentrationsLung parenchymaConsistent effect directionMolecular driversProteinGenetic analyses of chr11p15.5 region identify MUC5AC-MUC5B associated with asthma-related phenotypes
Li X, Li H, Christenson S, Castro M, Denlinger L, Erzurum S, Fahy J, Gaston B, Israel E, Jarjour N, Levy B, Mauger D, Moore W, Zein J, Kaminski N, Wenzel S, Woodruff P, Bleecker E, Meyers D, Program F. Genetic analyses of chr11p15.5 region identify MUC5AC-MUC5B associated with asthma-related phenotypes. Journal Of Asthma 2023, 60: 1824-1835. PMID: 36946148, PMCID: PMC10524756, DOI: 10.1080/02770903.2023.2193631.Peer-Reviewed Original ResearchMeSH KeywordsAsthmaCross-Sectional StudiesGenome-Wide Association StudyHumansMucin 5ACMucin-5BPhenotypeRNA, Messenger
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 analysisLongitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis: a genome-wide association study
Allen RJ, Oldham JM, Jenkins DA, Leavy OC, Guillen-Guio B, Melbourne CA, Ma SF, Jou J, Kim JS, Cooperative C, Fahy WA, Oballa E, Hubbard RB, Navaratnam V, Braybrooke R, Saini G, Roach KM, Tobin MD, Hirani N, Whyte MKB, Kaminski N, Zhang Y, Martinez FJ, Linderholm AL, Adegunsoye A, Strek ME, Maher TM, Molyneaux PL, Flores C, Noth I, Jenkins R, Wain LV. Longitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis: a genome-wide association study. The Lancet Respiratory Medicine 2022, 11: 65-73. PMID: 35985358, PMCID: PMC10077113, DOI: 10.1016/s2213-2600(22)00251-x.Peer-Reviewed Original ResearchMeSH KeywordsGenome-Wide Association StudyHumansIdiopathic Pulmonary FibrosisLungLung Volume MeasurementsVital CapacityConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisLung capacityAmerican Thoracic Society/European Respiratory Society guidelinesDiagnosis of IPFEuropean Respiratory Society guidelinesPotential novel therapeutic approachHealth-National HeartLongitudinal lung functionRespiratory Society guidelinesGenetic variantsNovel therapeutic approachesIncurable lung diseaseMedical Research CouncilProgressive scarringFVC declineLung functionVital capacityBlood InstituteSociety guidelinesLung diseaseNational HeartDisease progressionTherapeutic approachesSignificant association
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 roleAATFInjuryProteinLAMA3ExpressionAssemblyGenome-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
2017
Transcriptome profiles in sarcoidosis and their potential role in disease prediction
Schupp JC, Vukmirovic M, Kaminski N, Prasse A. Transcriptome profiles in sarcoidosis and their potential role in disease prediction. Current Opinion In Pulmonary Medicine 2017, 23: 487-492. PMID: 28590292, PMCID: PMC5637542, DOI: 10.1097/mcp.0000000000000403.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsGene Expression ProfilingGenome-Wide Association StudyHumansInterferon-gammaSarcoidosisSequence Analysis, RNASignal TransductionTh1 CellsTranscriptomeConceptsGenome-wide expression studiesWide expression studiesTranscriptome profilesTranscriptomic dataRNA sequencingExpression studiesGene expressionMolecular mechanismsLarge prospective followTh1 immune responseTranscriptomeNonnecrotizing granulomasProspective followSystemic diseaseDisease progressionTreatment outcomesImmune responseSarcoidosisPotential roleControl tissuesProgressive sarcoidosisKey roleDiseaseTranscriptomicsGranulomasExtreme 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
2013
Functional Genomic Assessment of Phosgene-Induced Acute Lung Injury in Mice
Leikauf GD, Concel VJ, Bein K, Liu P, Berndt A, Martin TM, Ganguly K, Jang AS, Brant KA, Dopico RA, Upadhyay S, Cario C, Di YP, Vuga LJ, Kostem E, Eskin E, You M, Kaminski N, Prows DR, Knoell DL, Fabisiak JP. Functional Genomic Assessment of Phosgene-Induced Acute Lung Injury in Mice. American Journal Of Respiratory Cell And Molecular Biology 2013, 49: 130522202035005. PMID: 23590305, PMCID: PMC3824050, DOI: 10.1165/rcmb.2012-0337oc.Peer-Reviewed Original ResearchMeSH KeywordsAcute Lung InjuryAllelesAnimalsChemical Warfare AgentsChromosome MappingElectrophoretic Mobility Shift AssayFemaleGene ExpressionGene Expression ProfilingGenomeGenome-Wide Association StudyGenomicsGenotypeIntegrinsLungMiceMice, Inbred StrainsOligonucleotide Array Sequence AnalysisPhosgenePolymorphism, Single NucleotidePromoter Regions, GeneticReelin ProteinSodium-Potassium-Exchanging ATPaseConceptsSignificant SNP associationsSNP associationsTranscriptomic analysisCompetitive electrophoretic mobility shift analysisGenome-wide association mappingFunctional genomic assessmentPutative transcription factorElectrophoretic mobility shift analysisMobility shift analysisAssociation mappingGenetic resolutionTranscription factorsCandidate genesFunctional domainsNonsynonymous SNPsGenomic assessmentPhenotypic differencesPhenotypic extremesDiverse panelGenesGenetic determinantsShift analysisPTPRTAllelesITGA9Genetic 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
2009
Chronic lung diseases
Wu W, Kaminski N. Chronic lung diseases. WIREs Mechanisms Of Disease 2009, 1: 298-308. PMID: 20835999, DOI: 10.1002/wsbm.23.Peer-Reviewed Original ResearchConceptsSystems biology approachBiology approachChronic lung diseaseComplex human diseasesHigh-throughput technologiesLung diseaseSystems biologyHuman diseasesTraditional experimental approachesComplex lung diseaseBiomedical researchExperimental approachSerious economic burdenHigh morbiditySerious threatHuman healthEconomic burdenMortality rateDiseaseBiologyMicroarrayPromising findings