Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma
Open Access
- 15 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-13
- https://doi.org/10.1038/s41467-020-15649-3
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.Keywords
Funding Information
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (R01HL133169, R01HL144790)
- U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (R01ES021801, R01ES025786, R01ES022282, R21ES024707, P30ES007048, P01ES022845)
- U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences
- U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
- U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (R21AI109059)
- U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences
- U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences
- U.S. Environmental Protection Agency (RD83544101)
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