New Research Unveils Surprising Links Between IPF and Comorbidities

Using a bidirectional Mendelian randomization (MR) strategy, a brand-new study that was recently published in the journal Chest discovered causal associations between idiopathic pulmonary fibrosis (IPF) and certain comorbidities.

Genetic susceptibility to venous thromboembolism (VTE), hypothyroidism, and gastroesophageal reflux disease (GERD) were found to increase the risk of IPF. Conversely, a decreased risk of IPF was linked to a genetic predisposition to chronic obstructive pulmonary disease (COPD).

In addition, the study found that IPF was associated with a lower risk of hypertension but a higher risk of lung cancer (suggestive protective effect).

“The most notable strength of this study is the ability of MR design to improve the causal inference, especially in the context of studying rare diseases (eg, IPF) where prospective cohort studies are always difficult to perform because of the inability to collect large samples,” the study’s authors explained.

While the evidence for VTE and hypothyroidism was only suggestive of an association with IPF, only GERD and COPD presented convincing evidence of their associations with IPF.

Lower genetically predicted forced expiratory volume in the first second (FEV1) and FEV1 to forced vital capacity (FVC) ratio, but not FVC, were linked to a lower risk of IPF in follow-up analyses of the primary findings, corroborating the causal relationship between COPD and IPF.

In addition, follow-up analyses supported the protective effect of IPF on hypertension by revealing negative associations between the genetic susceptibility to IPF and systolic, diastolic, and pulse pressure.

The remaining comorbidities—the study included 22 comorbidities for which genetic data was available—exhibited weak evidence of both inward and outward associations with IPF.

The authors acknowledged that estimates from Mendelian randomization studies may not be consistent with those from observational or interventional studies, despite the benefits of such studies.