Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis

作者：Harriet Corvol, Scott M. Blackman, Pierre‐Yves Boëlle, Paul J. Gallins, Rhonda G. Pace, Jaclyn R. Stonebraker, Frank J. Accurso, Annick Clément, Joseph Michael Collaco, Hong Dang, Anthony T. Dang, Arianna Franca, Jiafen Gong, Loïc Guillot, Katherine Lisa Keenan, Weili Li, Lin Fan, Michael V. Patrone, Karen S. Raraigh, Lei Sun, Yi‐Hui Zhou, Wanda K. O’Neal, Marci K. Sontag, Hara Levy, Peter R. Durie, Johanna M. Rommens, Mitchell L. Drumm, Fred A. Wright, Lisa J. Strug, Garry R. Cutting, Michael R. Knowles · 发表于：Nature Communications · 年份：2015 · DOI：10.1038/ncomms9382 · 被引用次数：303 · 研究领域：Cystic Fibrosis Research Advances、Epigenetics and DNA Methylation、Neonatal Respiratory Health Research

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.