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Cited by 222Asthma and respiratory diseasesGenetic Associations and EpidemiologyOccupational exposure and asthma

Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma

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Han, Yi, Jia, Qiong, Jahani, Pedram Shafiei, Hurrell, Benjamin P., Pan, Calvin, Huang, Pin, Gukasyan, Janet, Woodward, Nicholas C. +5 more·2020·Nature Communications
DOI 10.1038/s41467-020-15649-3PMC PMC7160128
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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.

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Authors
Han, Y., Jia, Q., Jahani, P. S., Hurrell, B. P., Pan, C., Huang, P., Gukasyan, J., Woodward, N. C., Eskin, E., Gilliland, F. D., Akbari, O., Hartiala, J. A., & Allayee, H.
Affiliations
  • University of Southern California (US)
  • University of California, Los Angeles (US)
Corresponding author
Allayee, Hooman
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-04-15
Volume
11
Issue
1
Pages
1776-1776
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-020-15649-3
PMC
PMC7160128
OpenAlex
W3017088606
Cited by
222
References
8
Citations by year
2026: 34 · 2025: 39 · 2024: 40 · 2023: 50 · 2022: 29 · 2021: 24 · 2020: 3 · 2019: 2 · 2013: 1
FWCI
3.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • 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)
  • Division of Intramural Research, National Institute of Allergy and Infectious Diseases (R21AI109059)
  • U.S. Environmental Protection Agency (RD83544101)
Topics
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Occupational exposure and asthma
Keywords
asthma, genetic architecture, immune pathways, CD52, open chromatin, immune cell gene expression, anti-CD52 antibody, airway hyperresponsiveness, allergic airway inflammation, causal gene prioritization
MeSH terms
CD52 Antigen, Adult, Aged, Animals, Asthma, Female, United Kingdom, Humans, Immune System, Lymphocytes, Male, Middle Aged, Risk Factors, Sex Factors, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Mice, Genome-Wide Association Study

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