Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

Fred A. Wright, Lisa J. Strug, Vishal K. Doshi, Clayton W. Commander, Scott Blackman, Lei Sun, Yves Berthiaume, David Cutler, Andreea Cojocaru, Michael Collaco, Mary Corey, Ruslan Dorfman, Katrina Goddard, Deanna Green, Jack W. Kent, Ethan M. Lange, Seunggeun Lee, Weili Li, Jingchun Luo, Gregory M. MayhewKathleen M. Naughton, Rhonda G. Pace, Peter Paré, Johanna M. Rommens, Andrew Sandford, Jaclyn R. Stonebraker, Wei Sun, Chelsea Taylor, Lori Vanscoy, Fei Zou, John Blangero, Julian Zielenski, Wanda K. O'Neal, Mitchell L. Drumm, Peter R. Durie, Michael R. Knowles, Garry R Cutting

Research output: Contribution to journalArticle


A combined genome-wide association and linkage study was used to identify loci causing variation in cystic fibrosis lung disease severity. We identified a significant association (P = 3.34 × 10-8) near EHF and APIP (chr11p13) in p.Phe508del homozygotes (n = 1,978). The association replicated in p.Phe508del homozygotes (P = 0.006) from a separate family based study (n = 557), with P = 1.49 × 10-9 for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family based study identified a significant quantitative trait locus on chromosome 20q13.2 (log 10 odds = 5.03). Our findings provide insight into the causes of variation in lung disease severity in cystic fibrosis and suggest new therapeutic targets for this life-limiting disorder.

Original languageEnglish (US)
Pages (from-to)539-546
Number of pages8
JournalNature Genetics
Issue number6
Publication statusPublished - Jun 2011


ASJC Scopus subject areas

  • Genetics

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