title: eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS-identified asthma genes.
abstract: BACKGROUND
  Genome-wide association studies (GWASs) have identified various genes associated with asthma, yet, causal genes or single nucleotide polymorphisms (SNPs) remain elusive. We sought to dissect functional genes/SNPs for asthma by combining expression quantitative trait loci (eQTLs) and GWASs.
  
  
  METHODS
  Cis-eQTL analyses of 34 asthma genes were performed in cells from human bronchial epithelial biopsy (BEC, n = 107) and from bronchial alveolar lavage (BAL, n = 94).
  
  
  RESULTS
  For TSLP-WDR36 region, rs3806932 (G allele protective against eosinophilic esophagitis) and rs2416257 (A allele associated with lower eosinophil counts and protective against asthma) were correlated with decreased expression of TSLP in BAL (P = 7.9 × 10(-11) and 5.4 × 10(-4) , respectively) and BEC, but not WDR36. Surprisingly, rs1837253 (consistently associated with asthma) showed no correlation with TSLP expression levels. For ORMDL3-GSDMB region, rs8067378 (G allele protective against asthma) was correlated with decreased expression of GSDMB in BEC and BAL (P = 1.3 × 10(-4) and 0.04) but not ORMDL3. rs992969 in the promoter region of IL33 (A allele associated with higher eosinophil counts and risk for asthma) was correlated with increased expression of IL33 in BEC (P = 1.3 × 10(-6) ) but not in BAL.
  
  
  CONCLUSIONS
  Our study illustrates cell-type-specific regulation of the expression of asthma-related genes documenting SNPs in TSLP, GSDMB, IL33, HLA-DQB1, C11orf30, DEXI, CDHR3, and ZBTB10 affect asthma risk through cis-regulation of its gene expression. Whenever possible, disease-relevant tissues should be used for transcription analysis. SNPs in TSLP may affect asthma risk through up-regulating TSLP mRNA expression or protein secretion. Further functional studies are warranted.
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Hastie
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Hawkins
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Moore
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Ampleford
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Milosevic
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, WI, USA.
authors.forename: W W
authors.initials: WW
authors.lastname: Busse
authors.affiliation: Department of Pathobiology, The Lerner Research Institute, Cleveland, OH, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Erzurum
authors.affiliation: Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
authors.forename: N
authors.initials: N
authors.lastname: Kaminski
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Wenzel
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Meyers
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Bleecker
mesh_terms: D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016022:Case-Control Studies; D002874:Chromosome Mapping; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008297:Male; D009928:Organ Specificity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000378:metabolism*
chemical_list: D007073:Immunoglobulin E
keywords: Genome-wide association studies; asthma susceptibility genes; bronchial alveolar lavage; bronchial epithelial cells; eQTL