2023
Examination of eQTL Polymorphisms Associated with Increased Risk of Progressive Complicated Sarcoidosis in European and African Descent Subjects.
Casanova N, Camp S, Gonzalez-Garay M, Batai K, Garman L, Montgomery C, Ellis N, Kittles R, Bime C, Hsu A, Holland S, Lussier Y, Karnes J, Sweiss N, Maier L, Koth L, Moller D, Kaminski N, Garcia J. Examination of eQTL Polymorphisms Associated with Increased Risk of Progressive Complicated Sarcoidosis in European and African Descent Subjects. European Journal Of Respiratory Medicine 2023, 5: 359-371. PMID: 38390497, PMCID: PMC10883688, DOI: 10.31488/ejrm.137.Peer-Reviewed Original ResearchExpression quantitative trait lociGenome-wide association studiesEQTL SNPsGenome-wide association study cohortsInnate immunityQuantitative trait lociAllograft rejection pathwayGWAS SNPsIndependent sarcoidosis cohortTrait lociAssociation studiesGenetic basisComplicated sarcoidosisSNPsHLA regionAfrican AmericansSarcoidosis riskSeverity of sarcoidosisGranulomatous inflammatory diseaseMHC class IISystemic granulomatous inflammatory diseaseEuropean AmericansSarcoidosis cohortVariants/genesPoolA 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 ResearchConceptsCell 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 ResearchConceptsGenome-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 driversProtein
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 ResearchConceptsTranscriptome-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
2021
S65 Genome-wide association study of survival times after diagnosis of idiopathic pulmonary fibrosis
Allen R, Oldham J, Lorenzo-Salazar J, Molyneaux P, Ma S, Stockwell A, Joseph C, Kim J, Guillen-Guio B, Hernandez-Beeftink T, Kropski J, Huang Y, Lee C, Adegunsoye A, Pugashetti J, Linderholm A, Vo V, Strek M, Hubbard R, Hirani N, Whyte M, Hart S, Nicholson A, Parfrey H, Rassl D, Wallace W, Fahy W, Valenzi E, Zhang Y, Kaminski N, Wolters P, Molina-Molina M, Martinez F, Hall I, Tobin, Maher T, Blackwell T, Yaspan B, Jenkins R, Flores C, Wain L, Noth I. S65 Genome-wide association study of survival times after diagnosis of idiopathic pulmonary fibrosis. Thorax 2021, 76: a43-a43. DOI: 10.1136/thorax-2021-btsabstracts.71.Peer-Reviewed Original ResearchGenome-wide analysisIdiopathic pulmonary fibrosisAssociation studiesGenome-wide association studiesGenetic variantsImportant biological processesWide association studyTwo-stage GWASIPF casesIPF survivalSurvival timeDisease progressionDNA regionsFirst GWASLikely genePulmonary fibrosisGene expressionBiological processesDiagnosis of IPFGenetic principal componentsProgression of IPFDisease riskStage 1Genetic determinantsCox proportional hazards modelS63 Genome-wide sex-by-SNP interaction analysis of susceptibility to idiopathic pulmonary fibrosis
Leavy O, Allen R, Oldham J, Guillen-Guio B, Stockwell A, Braybrooke R, Hubbard R, Ma S, Fingerlin T, Kaminski N, Zhang Y, Schwartz D, Yaspan B, Maher T, Molyneaux P, Flores C, Noth I, Jenkins R, Wain L. S63 Genome-wide sex-by-SNP interaction analysis of susceptibility to idiopathic pulmonary fibrosis. Thorax 2021, 76: a42-a42. DOI: 10.1136/thorax-2021-btsabstracts.69.Peer-Reviewed Original ResearchGenome-wide association studiesSNP interaction analysisIPF susceptibilityGenetic determinantsIndependent variantsIPF riskDifferent biological pathwaysGenetic lociSuggestive statistical significancePromoter regionBiological pathwaysAssociation studiesCommon genetic risk factorCase-control data setsGenetic componentIndependent datasetsInteraction analysisSignificant variantsSignificance thresholdBiological mechanismsSNP interactionsGenetic risk factorsEuropean descentFurther insightVariants
2020
Genome-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
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
Post-GWAS Prioritization Through Data Integration Provides Novel Insights on Chronic Obstructive Pulmonary Disease
Lu Q, Jin C, Sun J, Bowler R, Kechris K, Kaminski N, Zhao H. Post-GWAS Prioritization Through Data Integration Provides Novel Insights on Chronic Obstructive Pulmonary Disease. Statistics In Biosciences 2016, 9: 605-621. PMID: 27812370, PMCID: PMC5087812, DOI: 10.1007/s12561-016-9151-2.Peer-Reviewed Original ResearchGenome-wide association studiesFunctional annotationGenome-wide significance thresholdNovel insightsComplex human diseasesGWAS summary statisticsPotential risk locusComplex disease studiesEpigenomic annotationsGWAS signalsCOPD geneticsEnrichment analysisRisk lociIntegrative analysisAssociation studiesHuman diseasesGenetic contributionSignal prioritizationSignificance thresholdAnnotationUnprecedented opportunityBiological findingsData integrationLociSummary statistics
2015
eQTL 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
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
2011
Genome Wide Association Study In Idiopathic Pulmonary Fibrosis Identifies LCLAT1 As A Novel Candidate Gene
Noth I, Zhang Y, Barber M, Gibson K, Ma S, Lindell K, Kaminski N, Hysi P, Nicolae D, Garcia J. Genome Wide Association Study In Idiopathic Pulmonary Fibrosis Identifies LCLAT1 As A Novel Candidate Gene. 2011, a2266-a2266. DOI: 10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a2266.Peer-Reviewed Original Research