title: Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2.
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: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors: Fred A
authors: FA
authors: Wright
authors: Lisa J
authors: LJ
authors: Strug
authors: Vishal K
authors: VK
authors: Doshi
authors: Clayton W
authors: CW
authors: Commander
authors: Scott M
authors: SM
authors: Blackman
authors: Lei
authors: L
authors: Sun
authors: Yves
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authors: Berthiaume
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authors: Cutler
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authors: J Michael
authors: JM
authors: Collaco
authors: Mary
authors: M
authors: Corey
authors: Ruslan
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authors: Dorfman
authors: Katrina
authors: K
authors: Goddard
authors: Deanna
authors: D
authors: Green
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authors: JW
authors: Kent
authors: Ethan M
authors: EM
authors: Lange
authors: Seunggeun
authors: S
authors: Lee
authors: Weili
authors: W
authors: Li
authors: Jingchun
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authors: Luo
authors: Gregory M
authors: GM
authors: Mayhew
authors: Kathleen M
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authors: Naughton
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authors: Sandford
authors: Jaclyn R
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authors: Chelsea
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authors: Durie
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authors: Knowles
authors: Garry R
authors: GR
authors: Cutting
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