Jan 19, 2017

An Exome Sequencing Study to Assess the Role of Rare Genetic Variation in Pulmonary Fibrosis

American Journal of Respiratory and Critical Care Medicine
Slavé PetrovskiDavid B Goldstein

Abstract

Idiopathic pulmonary fibrosis (IPF) is an increasingly recognized, often fatal lung disease of unknown etiology. The aim of this study was to use whole-exome sequencing to improve understanding of the genetic architecture of pulmonary fibrosis. We performed a case-control exome-wide collapsing analysis including 262 unrelated individuals with pulmonary fibrosis clinically classified as IPF according to American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines (81.3%), usual interstitial pneumonia secondary to autoimmune conditions (11.5%), or fibrosing nonspecific interstitial pneumonia (7.2%). The majority (87%) of case subjects reported no family history of pulmonary fibrosis. We searched 18,668 protein-coding genes for an excess of rare deleterious genetic variation using whole-exome sequence data from 262 case subjects with pulmonary fibrosis and 4,141 control subjects drawn from among a set of individuals of European ancestry. Comparing genetic variation across 18,668 protein-coding genes, we found a study-wide significant (P < 4.5 × 10-7) case enrichment of qualifying variants in TERT, RTEL1, and PARN. A model qualifying ultrarare, deleterious, nonsy...Continue Reading

  • References36
  • Citations32

References

Mentioned in this Paper

Genome-Wide Association Study
Study
Pathogenic Aspects
Pathogenesis
Genes
PARN protein, human
Pulmonary Fibrosis
Myopathy
TERT gene
Dissecting Aneurysm of the Thoracic Aorta

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