Unknown

Dataset Information

0

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.

SUBMITTER: Han Y 

PROVIDER: S-EPMC7160128 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Han Yi Y   Jia Qiong Q   Jahani Pedram Shafiei PS   Hurrell Benjamin P BP   Pan Calvin C   Huang Pin P   Gukasyan Janet J   Woodward Nicholas C NC   Eskin Eleazar E   Gilliland Frank D FD   Akbari Omid O   Hartiala Jaana A JA   Allayee Hooman H  

Nature communications 20200415 1


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  ...[more]

Similar Datasets

| S-EPMC5980765 | biostudies-literature
| S-EPMC7077504 | biostudies-literature
| S-EPMC5315525 | biostudies-literature
| S-EPMC6205839 | biostudies-literature
| S-EPMC7772222 | biostudies-literature
| S-EPMC8571093 | biostudies-literature
| S-EPMC8831901 | biostudies-literature
| S-EPMC8441299 | biostudies-literature
| S-EPMC7999653 | biostudies-literature
| S-EPMC6753136 | biostudies-literature