title: Airway Epithelial Expression Quantitative Trait Loci Reveal Genes Underlying Asthma and Other Airway Diseases.
abstract: Genome-wide association studies (GWASs) have identified loci that are robustly associated with asthma and related phenotypes; however, the molecular mechanisms underlying these associations need to be explored. The most relevant tissues to study the functional consequences of asthma are the airways. We used publically available data to derive expression quantitative trait loci (eQTLs) for human epithelial cells from small and large airways and applied the eQTLs in the interpretation of GWAS results of asthma and related phenotypes. For the small airways (n = 105), we discovered 660 eQTLs at a 10% false discovery rate (FDR), among which 315 eQTLs were not previously reported in a large-scale eQTL study of whole lung tissue. A large fraction of the identified eQTLs is supported by data from Encyclopedia of DNA Elements (ENCODE) showing that the eQTLs reside in regulatory elements (57.5 and 67.6% of cis- and trans-eQTLs, respectively). Published pulmonary GWAS hits were enriched as airway epithelial eQTLs (9.2-fold). Further, genes regulated by asthma GWAS loci in epithelium are significantly enriched in immune response pathways, such as IL-4 signaling (FDR, 5.2 × 10(-4)). The airway epithelial eQTLs described in this study are complementary to previously reported lung eQTLs and represent a powerful resource to link GWAS-associated variants to their regulatory function and thus elucidate the molecular mechanisms underlying asthma and airway-related conditions.
authors.affiliation: 1 College of Computer Science and Technology, Huaqiao University, Xiamen, China.|2 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.affiliation: 3 The University of British Columbia Center for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada.|4 Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ma'en
authors.initials: M
authors.lastname: Obeidat
authors.affiliation: 2 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.|5 Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Antonio Fabio
authors.initials: AF
authors.lastname: Di Narzo
authors.affiliation: 2 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.|5 Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.affiliation: 3 The University of British Columbia Center for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada.|4 Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.affiliation: 3 The University of British Columbia Center for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada.|4 Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
authors.affiliation: 2 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.|5 Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York; and.|6 Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Hao
mesh_terms: D001249:Asthma / Q000235:genetics*; D019295:Computational Biology; D030541:Databases, Genetic; D004847:Epithelial Cells / Q000737:chemistry*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D020545:Respiratory Mucosa / Q000737:chemistry*
chemical_list: D005819:Genetic Markers
keywords: airway diseases; airway epithelium; asthma; expression quantitative trait loci