Biomaterial Database

Nasal airway transcriptome-wide association study of asthma reveals genetically driven mucus pathobiology. 2022

Satria P Sajuthi, and Jamie L Everman, and Nathan D Jackson, and Benjamin Saef, and Cydney L Rios, and Camille M Moore, and Angel C Y Mak, and Celeste Eng, and Ana Fairbanks-Mahnke, and Sandra Salazar, and Jennifer Elhawary, and Scott Huntsman, and Vivian Medina, and Deborah A Nickerson, and Soren Germer, and Michael C Zody, and Gonçalo Abecasis, and Hyun Min Kang, and Kenneth M Rice, and Rajesh Kumar, and Noah A Zaitlen, and Sam Oh, and , and José Rodríguez-Santana, and Esteban G Burchard, and Max A Seibold

Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.

To identify genetic determinants of airway dysfunction, we performed a transcriptome-wide association study for asthma by combining RNA-seq data from the nasal airway epithelium of 681 children, with UK Biobank genetic association data. Our airway analysis identified 95 asthma genes, 58 of which were not identified by transcriptome-wide association analyses using other asthma-relevant tissues. Among these genes were MUC5AC, an airway mucin, and FOXA3, a transcriptional driver of mucus metaplasia. Muco-ciliary epithelial cultures from genotyped donors revealed that the MUC5AC risk variant increases MUC5AC protein secretion and mucus secretory cell frequency. Airway transcriptome-wide association analyses for mucus production and chronic cough also identified MUC5AC. These cis-expression variants were associated with trans effects on expression; the MUC5AC variant was associated with upregulation of non-inflammatory mucus secretory network genes, while the FOXA3 variant was associated with upregulation of type-2 inflammation-induced mucus-metaplasia pathway genes. Our results reveal genetic mechanisms of airway mucus pathobiology.

UI	MeSH Term	Description	Entries
D008679	Metaplasia	A condition in which there is a change of one adult cell type to another similar adult cell type.
D009093	Mucus	The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells.
D002648	Child	A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL.	Children
D004848	Epithelium	The layers of EPITHELIAL CELLS which cover the inner and outer surfaces of the cutaneous, mucus, and serous tissues and glands of the body.	Mesothelium,Epithelial Tissue,Mesothelial Tissue,Epithelial Tissues,Mesothelial Tissues,Tissue, Epithelial,Tissue, Mesothelial,Tissues, Epithelial,Tissues, Mesothelial
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001249	Asthma	A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).	Asthma, Bronchial,Bronchial Asthma,Asthmas
D055271	Mucin 5AC	A gel-forming mucin that is primarily found on the surface of gastric epithelium and in the RESPIRATORY TRACT. Mucin 5AC was originally identified as two distinct proteins, however a single gene encodes the protein which gives rise to the mucin 5A and mucin 5C variants.	Mucin 5A,Mucin 5C
D059467	Transcriptome	The pattern of GENE EXPRESSION at the level of genetic transcription in a specific organism or under specific circumstances in specific cells.	Transcriptomes,Gene Expression Profiles,Gene Expression Signatures,Transcriptome Profiles,Expression Profile, Gene,Expression Profiles, Gene,Expression Signature, Gene,Expression Signatures, Gene,Gene Expression Profile,Gene Expression Signature,Profile, Gene Expression,Profile, Transcriptome,Profiles, Gene Expression,Profiles, Transcriptome,Signature, Gene Expression,Signatures, Gene Expression,Transcriptome Profile