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Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2 |
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| 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 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 |
| Affiliation: | Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. |
| 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. |
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