A whole genome sequencing study of moderate to severe asthma identifies a lung function locus associated with asthma risk

Autor: Diana Chang, Julie Hunkapiller, Tushar Bhangale, Jens Reeder, Kiran Mukhyala, Jennifer Tom, Amy Cowgill, Jan Vogel, William F. Forrest, Zia Khan, Amy Stockwell, Mark I. McCarthy, Tracy L. Staton, Julie Olsson, Cecile T. J. Holweg, Dorothy S. Cheung, Hubert Chen, Matthew J. Brauer, Robert R. Graham, Timothy Behrens, Mark S. Wilson, Joseph R. Arron, David F. Choy, Brian L. Yaspan
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Scientific Reports, Vol 12, Iss 1, Pp 1-11 (2022)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-022-09447-8
Popis: Abstract Genome-wide association studies (GWAS) have identified many common variant loci associated with asthma susceptibility, but few studies investigate the genetics underlying moderate-to-severe asthma risk. Here, we present a whole-genome sequencing study comparing 3181 moderate-to-severe asthma patients to 3590 non-asthma controls. We demonstrate that asthma risk is genetically correlated with lung function measures and that this component of asthma risk is orthogonal to the eosinophil genetics that also contribute to disease susceptibility. We find that polygenic scores for reduced lung function are associated with younger asthma age of onset. Genome-wide, seven previously reported common asthma variant loci and one previously reported lung function locus, near THSD4, reach significance. We replicate association of the lung function locus in a recently published GWAS of moderate-to-severe asthma patients. We additionally replicate the association of a previously reported rare (minor allele frequency
Databáze: Directory of Open Access Journals
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