Large-scale Genetic Analysis Identifies 66 Novel Loci for Asthma
Han, Y.; Jia, Q.; Shafiei Jahani, P.; Hurrell, B. P.; Pan, C.; Huang, P.; Gukasyan, J.; Woodward, N. C.; Eskin, E.; Gilliland, F.; Akbari, O.; Hartiala, J. A.; Allayee, H.
Show abstract
We carried out a genome-wide association study (GWAS) for asthma in UK Biobank, followed by a meta-analysis with results from the Trans-National Asthma Genetic Consortium (TAGC). 66 novel genomic regions were identified, bringing the number of known asthma susceptibility loci to 211. Significant gene-sex interactions were also observed where susceptibility alleles, either individually or as a function of polygenic risk scores, increased asthma risk to a greater extent in men than women. Bioinformatics analyses demonstrated that asthma-associated variants were enriched for colocalizing to regions of open chromatic in immune cells and identified candidate causal genes at 52 of the novel loci, including CD52. An anti-CD52 (-CD52) antibody mimicked the immune cell-depleting effects of an FDA-approved human -CD52 antibody and reduced allergen-induced airway hyperreactivity in mice. These results further elucidate the genetic architecture of asthma, provide evidence that the immune system plays a prominent role in its pathogenesis, and suggest that CD52 represents a potentially novel therapeutic target for treating asthma.
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