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

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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.

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

publication date

  • June 2011