학술논문
A whole genome sequencing study of moderate to severe asthma identifies a lung function locus associated with asthma risk
Document Type
article
Author
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
Source
Scientific Reports, Vol 12, Iss 1, Pp 1-11 (2022)
Subject
Language
English
ISSN
2045-2322
Abstract
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