Title: Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma.
Authors: Han, Yi; Jia, Qiong; Jahani, Pedram Shafiei; Hurrell, Benjamin P; Pan, Calvin; Huang, Pin; Gukasyan, Janet; Woodward, Nicholas C; Eskin, Eleazar; Gilliland, Frank D; Akbari, Omid; Hartiala, Jaana A; Allayee, Hooman
Published In Nat Commun, (2020 04 15)
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.
PubMed ID: 32296059
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