A new study published in Chest found causal associations between idiopathic pulmonary fibrosis (IPF) and certain comorbidities, using a bidirectional Mendelian randomization (MR) approach.

According to the results, genetic liability to gastroesophageal reflux disease (GERD), venous thromboembolism (VTE), and hypothyroidism were associated with increased risk of IPF. Conversely, genetic liability to chronic obstructive pulmonary disease (COPD) was associated with decreased risk of IPF.

Furthermore, the study identified causal associations between IPF and increased risk of lung cancer (suggestive detrimental effect), but reduced risk of hypertension (suggestive protective effect).

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“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.

Only GERD and COPD showed convincing evidence of their associations with IPF, while for VTE and hypothyroidism the evidence was just suggestive of association with IPF.

Read about IPF comorbidities

Follow-up analyses of principal findings further supported the causal effect of COPD on IPF as lower genetically predicted forced expiratory volume in the first second (FEV1) and FEV1 to forced vital capacity (FVC) ratio, but not FVC, were associated with reduced risk of IPF.

Moreover, follow-up analyses revealed negative associations between the genetic liability to IPF and systolic and diastolic blood pressure, as well as pulse pressure, which supports the protective effect of IPF on hypertension.

The remaining comorbidities—the study included a total of 22 comorbidities with genetic data available—showed weak evidence of associations with IPF in both directions.

Despite the advantages of Mendelian randomization studies, the authors recognized that estimates from such studies may not be consistent with those obtained from observational or interventional studies.


Zhu J, Zhou D, Wang J, et al. A causal atlas on comorbidities in idiopathic pulmonary fibrosis: a bidirectional Mendelian randomization study. Chest. Published online March 10, 2023. doi:10.1016/j.chest.2023.02.038