Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis
Year: 2020
Type: article
Study design: Observational Study
Abstract: The identification of small molecules that target specific CFTR variants has ushered in a new era of treatment for cystic fibrosis (CF), yet optimal, individualized treatment of CF will require identification and targeting of disease modifiers. Here we use genome-wide association analysis to identify genetic modifiers of CF lung disease, the primary cause of mortality. Meta-analysis of 6,365 CF patients identifies five loci that display significant association with variation in lung disease. Regions on chr3q29 (MUC4/MUC20; P=3.3 × 10−11), chr5p15.3 (SLC9A3; P=6.8 × 10−12), chr6p21.3 (HLA Class II; P=1.2 × 10−8) and chrXq22-q23 (AGTR2/SLC6A14; P=1.8 × 10−9) contain genes of high biological relevance to CF pathophysiology. The fifth locus, on chr11p12-p13 (EHF/APIP; P=1.9 × 10−10), was previously shown to be associated with lung disease. These results provide new insights into potential targets for modulating lung disease severity in CF.
DOI: 10.17615/zm8z-dt22
Authors: Knowles, Michael R., Lin, Fan, Sontag, Marci K., Collaco, Joseph M., Patrone, Michael V., Boëlle, Pierre-Yves, Gallins, Paul J., Pace, Rhonda G., Levy, Hara, Franca, Arianna, Dang, Anthony T., Keenan, Katherine, Blackman, Scott M., Zhou, Yi-Hui, Rommens, Johanna M., Raraigh, Karen S., Stonebraker, Jaclyn R., Accurso, Frank J., Wright, Fred A., Dang, Hong, Guillot, Loic, Sun, Lei, Li, Weili, Clement, Annick, Cutting, Garry R., O’Neal, Wanda K., Strug, Lisa J., Durie, Peter R., Gong, Jiafen, Drumm, Mitchell L.
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4298176409