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

FA Wright, LJ Strug, VK Doshi, CW Commander… - Nature …, 2011 - nature.com
FA Wright, LJ Strug, VK Doshi, CW Commander, SM Blackman, L Sun, Y Berthiaume…
Nature genetics, 2011nature.com
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 …
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 (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.
nature.com