Novel variation at chr11p13 associated with cystic fibrosis lung disease severity

Hong Dang; Paul J Gallins; Rhonda G Pace; Xue-Liang Guo; Jaclyn R Stonebraker; Harriet Corvol; Garry R Cutting; Mitchell L Drumm; Lisa J Strug; Michael R Knowles; Wanda K O'Neal

doi:10.1038/hgv.2016.20

Novel variation at chr11p13 associated with cystic fibrosis lung disease severity

Hum Genome Var. 2016 Jul 7:3:16020. doi: 10.1038/hgv.2016.20. eCollection 2016.

Authors

Affiliations

¹ Marsico Lung Institute, CF/Pulmonary Research and Treatment Center, School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC, USA.
² Bioinformatics Research Center, North Carolina State University , Raleigh, NC, USA.
³ Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Trousseau, Pediatric Pulmonary Department, Institut National de la Santé et la Recherche Médicale (INSERM) U938, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06, Paris, France.
⁴ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Pediatrics, School of Medicine, Case Western Reserve University , Cleveland, OH, USA.
⁶ Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.

Abstract

Published genome-wide association studies (GWASs) identified an intergenic region with regulatory features on chr11p13 associated with cystic fibrosis (CF) lung disease severity. Targeted resequencing in n=377, followed by imputation to n=6,365 CF subjects, was used to identify unrecognized genetic variants (including indels and microsatellite repeats) associated with phenotype. Highly significant associations were in strong linkage disequilibrium and were seen only in Phe508del homozygous CF subjects, indicating a CFTR genotype-specific mechanism.

Abstract

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