We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2.
- Authors
Wright, Fred A; Strug, Lisa J; Doshi, Vishal K; Commander, Clayton W; Blackman, Scott M; Sun, Lei; Berthiaume, Yves; Cutler, David; Cojocaru, Andreea; Collaco, J Michael; Corey, Mary; Dorfman, Ruslan; Goddard, Katrina; Green, Deanna; Kent, Jack W, Jr; Lange, Ethan M; Lee, Seunggeun; Li, Weili; Luo, Jingchun; Mayhew, Gregory M; Naughton, Kathleen M; Pace, Rhonda G; Paré, Peter; Rommens, Johanna M; Sandford, Andrew; Stonebraker, Jaclyn R; Sun, Wei; Taylor, Chelsea; Vanscoy, Lori L; Zou, Fei; Blangero, John; Zielenski, Julian; O'Neal, Wanda K; Drumm, Mitchell L; Durie, Peter R; Knowles, Michael R; Cutting, Garry R
- Abstract
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.
- Publication
Nature genetics, 2011, Vol 43, Issue 6, p539
- ISSN
1546-1718
- Publication type
Journal Article
- DOI
10.1038/ng.838