| Title: | Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma |
| Journal: | Nature Communications |
| Published: | 15 Apr 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32296059/ |
| DOI: | https://doi.org/10.1038/s41467-020-15649-3 |
| URL: | https://www.nature.com/articles/s41467-020-15649-3.pdf |
| Citations: | 138 (76 in last 2 years) as of 8 Aug 2024 |
Publication 3429
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Abstract
Asthma is a chronic and genetically complex respiratory disease that affects over 300 million people worldwide. Here, we report a genome-wide analysis for asthma using data from the UK Biobank and the Trans-National Asthma Genetic Consortium. We identify 66 previously unknown asthma loci and demonstrate that the susceptibility alleles in these regions are, either individually or as a function of cumulative genetic burden, associated with risk to a greater extent in men than women. Bioinformatics analyses prioritize candidate causal genes at 52 loci, including CD52, and demonstrate that asthma-associated variants are enriched in regions of open chromatin in immune cells. Lastly, we show that a murine anti-CD52 antibody mimics the immune cell-depleting effects of a clinically used human anti-CD52 antibody and reduces allergen-induced airway hyperreactivity in mice. These results further elucidate the genetic architecture of asthma and provide important insight into the immunological and sex-specific relevance of asthma-associated risk variants.13 Authors
- Yi Han
- Qiong Jia
- Pedram Shafiei Jahani
- Benjamin P. Hurrell
- Calvin Pan
- Pin Huang
- Janet Gukasyan
- Nicholas C. Woodward
- Eleazar Eskin
- Frank D. Gilliland
- Omid Akbari
- Jaana A. Hartiala
- Hooman Allayee
1 Application
| Application ID | Title |
|---|---|
| 33307 | Sex-specific Genetic Determinants of Cardiometabolic Traits |
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