Authors:
Fred A Wright, Lisa J Strug, Vishal K Doshi, Clayton W Commander, Scott M Blackman, Lei Sun, Yves Berthiaume, David Cutler, Andreea Cojocaru, J Michael Collaco, Mary Corey, Ruslan Dorfman, Katrina Goddard, Deanna Green, Jack W Kent Jr, Ethan M Lange, Seunggeun Lee, Weili Li, Jingchun Luo, Gregory M Mayhew, Kathleen M Naughton, Rhonda G Pace, Peter Paré, Johanna M Rommens, Andrew Sandford, Jaclyn R Stonebraker, Wei Sun, Chelsea Taylor, Lori L Vanscoy, Fei Zou, John Blangero, Julian Zielenski, Wanda K O'Neal, Mitchell L Drumm, Peter R Durie, Michael R Knowles, & Garry R Cutting
Summary:
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 (log10 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.
Source:
Nature Genetics; 43, 539-546 (05/22/11)