Genetics and Genomics of Pulmonary Fibrosis: Charting the Molecular Landscape and Shaping Precision Medicine

Adegunsoye, Ayodeji; Kropski, Jonathan A.; Behr, Juergen; Blackwell, Timothy S.; Corte, Tamera J.; Cottin, Vincent; Glanville, Allan R.; Glassberg, Marilyn K.; Griese, Matthias; Hunninghake, Gary M.; Johannson, Kerri A.; Keane, Michael P.; Kim, John S.; Kolb, Martin; Maher, Toby M.; Oldham, Justin M.; Podolanczuk, Anna J.; Rosas, Ivan O.; Martinez, Fernando J.; Noth, Imre; Schwartz, David A.

doi:10.1164/rccm.202401-0238so

Cited by 2 publications

(1 citation statement)

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“…Ayodeji Adegunsoye et al generalized that under the regulation of some harmful environmental factors such as smoking, diet, viral infection, and ambient air pollutants, individuals with genetic variation are more susceptible to pulmonary fibrosis (PF) through epigenetic modifications such as DNA methylation, which is referred to as the gene–environment interaction. Among them, the variations of the MUC5B promoter are one of the most common genetic risk factors of early and established PF ( Adegunsoye et al, 2024 ). Similarly, a seminal study by Juge et al in France showed that the MUC5B promoter variant is associated with an increased risk of developing ILD in patients with RA ( Juge et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Genetic evidence reveals a causal relationship between rheumatoid arthritis and interstitial lung disease

Zhao,

Zhang,

Guo

et al. 2024

Front. Genet.

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Background/purpose: Previous epidemiological studies have associated interstitial lung disease (ILD) with rheumatoid arthritis (RA), yet the causality of this relationship remains uncertain. This study aimed to investigate the genetic causal link between ILD and RA.Methods: Genome-wide association study (GWAS) statistics for ILD and RA were collected from public datasets. Relevant single-nucleotide polymorphisms (SNPs) were selected by executing quality control steps from the GWAS summary results. A two-sample bidirectional Mendelian randomization (MR) analysis was performed to assess the causal relationship between the two conditions. The MR analysis primarily used the inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression methods. Sensitivity analyses, including MR-Egger, leave-one-out, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), were conducted to evaluate the heterogeneity and pleiotropy. Replication analyses using Asian datasets were also conducted to enhance the robustness of our findings.Results: In the European population, RA was found to increase the risk of ILD by 9.6% (OR: 1.096, 95% CI: 1.023–1.174, p = 0.009). Conversely, ILD was associated with a 12.8% increased risk of RA (OR: 1.128, 95% CI: 1.013–1.256, p = 0.029). Replication analyses from Asian GWAS further supported these findings, particularly the increased risk of ILD attributable to RA (OR: 1.33, 95% CI: 1.18–1.49, p-value <0.001).Conclusion: Our findings underscore the clinical importance of screening for ILD in RA patients and suggest that effective management of RA could significantly benefit ILD patients. The potential applicability of novel RA treatments to ILD warrants further exploration. Additionally, racial disparities in the manifestation of these diseases should not be overlooked, as they may offer new perspectives for targeted therapies in diverse populations.

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Section: Discussionmentioning

confidence: 99%