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

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 and Hooman Allayee ()
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Yi Han: University of Southern California
Qiong Jia: University of Southern California
Pedram Shafiei Jahani: University of Southern California
Benjamin P. Hurrell: University of Southern California
Calvin Pan: David Geffen School of Medicine at UCLA
Pin Huang: University of Southern California
Janet Gukasyan: University of Southern California
Nicholas C. Woodward: University of Southern California
Eleazar Eskin: University of California, Los Angeles
Frank D. Gilliland: University of Southern California
Omid Akbari: University of Southern California
Jaana A. Hartiala: University of Southern California
Hooman Allayee: University of Southern California

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15649-3

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DOI: 10.1038/s41467-020-15649-3

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