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

Nat Commun. 2020 Apr 15;11(1):1776. doi: 10.1038/s41467-020-15649-3.


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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

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


  • CD52 Antigen

Associated data

  • figshare/10.6084/m9.figshare.11955108