Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma.
Yi HanQiong JiaPedram Shafiei JahaniBenjamin P HurrellCalvin PanPin HuangJanet GukasyanNicholas C WoodwardEleazar EskinFrank D GillilandOmid AkbariJaana A HartialaHooman AllayeePublished in: Nature communications (2020)
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.
Keyphrases
- chronic obstructive pulmonary disease
- lung function
- genome wide
- allergic rhinitis
- copy number
- genome wide analysis
- gene expression
- type diabetes
- cystic fibrosis
- oxidative stress
- metabolic syndrome
- dna damage
- machine learning
- endothelial cells
- skeletal muscle
- risk factors
- quality improvement
- electronic health record
- cross sectional
- pregnant women
- nk cells
- deep learning
- high fat diet induced
- pregnancy outcomes
- genome wide association study