Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants

Area of Science:

• Genetics
• Pulmonology
• Rare Diseases

Background:

• Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible lung disease.
• Both common genetic variants and environmental factors are linked to IPF.
• The contribution of rare, genome-wide genetic variants to IPF risk is not fully understood.

Purpose of the Study:

• To investigate the role of rare genetic variants across the genome in IPF risk.
• To identify specific genes and variants associated with IPF susceptibility.

Main Methods:

• Whole-genome sequencing of 2,180 IPF cases was performed.
• Association testing focused on aggregated rare variants (MAF ≤0.01) within genes/regions.
• Heritability of IPF was estimated using common and rare variants.

Main Results:

• Rare variants in TERT and RTEL1 genes showed significant association with IPF.
• A single rare variant in TERT and one in RTEL1 consistently influenced association statistics.
• SNP heritability for IPF was estimated at 32%.

Conclusions:

• Rare variants in TERT and RTEL1, along with known common variants, are major contributors to IPF risk.
• Future IPF risk profiling and therapy development should consider TERT, RTEL1, common variants, and environmental factors.