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

Harriet Corvol, Scott M. Blackman, Pierre Yves Boëlle, Paul J. Gallins, Rhonda G. Pace, Jaclyn R. Stonebraker, Frank J. Accurso, Annick Clement, Joseph M. Collaco, Hong Dang, Anthony T. Dang, Arianna Franca, Jiafen Gong, Loic Guillot, Katherine Keenan, Weili Li, Fan Lin, Michael V. Patrone, Karen S. Raraigh, Lei SunYi Hui Zhou, Wanda K. Wanda, 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

Research output: Contribution to journalArticlepeer-review

156 Scopus citations


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.

Original languageEnglish (US)
Article number8382
JournalNature communications
StatePublished - Sep 29 2015

ASJC Scopus subject areas

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology


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