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

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.

• 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
• Journal: Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 1776 (04 15 2020) ISSN: 2041-1723 [Electronic] England
• PMID: 32296059 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• CD52 Antigen

Topics

• Adult
• Aged
• Animals
• Asthma (genetics, immunology)
• CD52 Antigen (genetics, immunology)
• Case-Control Studies
• Female
• Genetic Predisposition to Disease (epidemiology)
• Genome-Wide Association Study
• Humans
• Immune System (cytology, pathology)
• Lymphocytes (metabolism)
• Male
• Mice
• Middle Aged
• Polymorphism, Single Nucleotide
• Quantitative Trait Loci
• Risk Factors
• Sex Factors
• United Kingdom (epidemiology)