Back to Search
Start Over
Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-11 (2020), Nature Communications
- Publication Year :
- 2020
- Publisher :
- Nature Portfolio, 2020.
-
Abstract
- Publisher's version (útgefin grein)<br />Asthma is one of the most common chronic diseases affecting both children and adults. We report a genome-wide association meta-analysis of 69,189 cases and 702,199 controls from Iceland and UK biobank. We find 88 asthma risk variants at 56 loci, 19 previously unreported, and evaluate their effect on other asthma and allergic phenotypes. Of special interest are two low frequency variants associated with protection against asthma; a missense variant in TNFRSF8 and 3‘ UTR variant in TGFBR1. Functional studies show that the TNFRSF8 variant reduces TNFRSF8 expression both on cell surface and in soluble form, acting as loss of function. eQTL analysis suggests that the TGFBR1 variant acts through gain of function and together with an intronic variant in a downstream gene, SMAD3, points to defective TGFβR1 signaling as one of the biological perturbations increasing asthma risk. Our results increase the number of asthma variants and implicate genes with known role in T cell regulation, inflammation and airway remodeling in asthma pathogenesis.<br />We thank the individuals who participated in this study and the staff at the Icelandic Patient Recruitment Center and the deCODE genetics core facilities. Further to all our colleagues who contributed to the data collection and phenotypic characterization of clinical samples as well as to the genotyping and analysis of the whole-genome association data. This research has been conducted using the UK biobank Resource under Application Number ‘24711’.
- Subjects :
- 0301 basic medicine
T-Lymphocytes
Iceland
Receptor, Transforming Growth Factor-beta Type I
General Physics and Astronomy
Genome-wide association study
02 engineering and technology
Genome-wide association studies
Pathogenesis
Leukocyte Count
Missense mutation
lcsh:Science
3' Untranslated Regions
Multidisciplinary
Gen
021001 nanoscience & nanotechnology
Phenotype
Astmi
3. Good health
medicine.anatomical_structure
Airway Remodeling
0210 nano-technology
Erfðarannsóknir
T cell
Science
Quantitative Trait Loci
T cells
Ki-1 Antigen
Polymorphism, Single Nucleotide
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Immunogenetics
medicine
Humans
Genetic Predisposition to Disease
Loss function
Asthma
business.industry
General Chemistry
medicine.disease
United Kingdom
respiratory tract diseases
Eosinophils
MicroRNAs
Meta-analysis
Genarannsóknir
030104 developmental biology
Expression quantitative trait loci
Immunology
lcsh:Q
Gene expression
business
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....d8937da5d736ab2c1898f89a0970b406