Genetics of fibrosing interstitial lung diseases

Interstitial lung diseases (ILD) are a group of complex diseases characterized by inflammation and/or fibrosis of the lung interstitium. Idiopathic pulmonary fibrosis (IPF), the most common and aggressive form of ILD, has been at the central stage in genetic studies. To disentangle its genetic architecture and advance in developing precision medicine approaches for better care of patients, the studies have mostly relied on genome-wide association studies. Next-generation sequencing studies have also accelerated our understanding of IPF genetics, with approaches involving family studies and population-scale analyses. The emerging picture supports that IPF is governed by more than 30 genetic loci linked to telomere dysfunction, host defense, transforming growth factor-beta signaling, cell-cell adhesion, and mitotic spindle assembly, involving rare and common genetic variation, exerting non-additive effects in patient trajectories. In contrast, genetic research into non-IPF did not keep up the pace. However, a significant genetic overlap in terms of susceptibility and progression has been observed between IPF and other ILD subtypes. In this review, we summarize the main findings published in the literature and discuss their potential utility for diagnosis, risk stratification, and prognosis.