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

Julian Zielenski,Seunggeun Lee,Weili Li,Michael R Knowles ,John Blangero,Joseph M Collaco ,Vishal Doshi ,Chelsea Taylor,Rhonda G Pace ,Lisa J Strug ,Wei Sun,Peter R Durie ,Deanna Green,Yves Berthiaume,Lori L Vanscoy ,Ruslan Dorfman,Johanna M Rommens ,Mitchell L Drumm ,Katrina A.b Goddard ,Gregory M Mayhew ,Kathleen M Naughton ,Jack W Kent ,David J Cutler ,Andreea Cojocaru,Mary Corey,Clayton W Commander ,Scott M Blackman ,Ethan M Lange ,Jaclyn R Stonebraker ,Fred A Wright ,Garry R Cutting ,Jingchun Luo,Wanda K O’neal ,Fei Zou,Andrew J Sandford ,Peter D Paré ,Lei Sun

doi:10.1038/ng.838

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

Julian Zielenski, Seunggeun Lee + Show 35 more

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https://doi.org/10.1038/ng.838

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Journal: Nature Genetics	Publication Date: May 22, 2011
Citations: 257	License type: unspecified-oa

Affiliation: Hospital for Sick Children, University of North Carolina at Chapel Hill, Institute for Clinical Evaluative Sciences, SickKids Foundation, Texas Biomedical Research Institute, Johns Hopkins Medicine, Johns Hopkins University, Public Health Ontario, University of Toronto, Centre Hospitalier de l’Université de Montréal, Naval Medical Center Portsmouth, Case Western Reserve University, Pediatrics and Genetics, Oregon Clinic, Emory University, University of British Columbia

#Disease Severity In Cystic Fibrosis #Cystic Fibrosis Lung Disease Severity + Show 8 more

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Abstract

A combined genome-wide association and linkage study was used to identify loci causing variation in CF lung disease severity. A significant association (P=3. 34 × 10-8) near EHF and APIP (chr11p13) was identified in F508del homozygotes (n=1,978). The association replicated in F508del 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 QTL on chromosome 20q13.2 (LOD=5.03). Our findings provide insight into the causes of variation in lung disease severity in CF and suggest new therapeutic targets for this life-limiting disorder.

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