Study probes genetic links between asthma and COPD overlap


A small proportion of patients have symptoms of both asthma and chronic obstructive pulmonary disease. A new report suggests there may be an intermediate phenotype.

A new report has identified 8 genetic signals associated with the overlap of asthma and chronic obstructive pulmonary disease (COPD), suggesting that there is a range of genetic influences that predispose some people to exhibit symptoms of both conditions.

Asthma and COPD are 2 different diseases, but they share certain characteristics. In a new study published in Chest, corresponding author Catherine John of the University of Leicester and colleagues explained that a subset of patients have symptoms consistent with both asthma and COPD. Evidence suggests that these patients end up with significantly worse outcomes than patients with either disease.

Previous research has sought to examine potential genetic links between the 2 diseases, but it is unclear exactly how the 2 are related. John and his colleagues wanted to better understand the genetic architecture at play in the asthma-COPD overlap and determine whether genetic risk factors for overlapping symptoms differ from risk factors for individual diseases.

To do this, they conducted a genome-wide association study of 8,068 people with asthma-COPD overlap and more than 40,000 controls without asthma or COPD. After identifying promising genetic signals in a genetic database, they compared the asthma-COPD group with asthma-only controls and with COPD-only controls to look for patterns and similarities.

The first phase of the research produced 31 independent variables that the investigators felt warranted further investigation. This review led to the discovery of 8 new signals that they believed were associated with the asthma-COPD overlap.

“These signals suggest an array of shared genetic influences, with some primarily influencing asthma (FAM105A, GLB1, PHB, TSLP), others mainly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1),” John and his colleagues wrote.

They further identified 1 intergenic signal, located on chromosome 5, which they believed had never been associated with either of these conditions, or with lung function in general.

The researchers said the results demonstrate a strong genetic correlation between the asthma-COPD overlap and COPD/lung function, as well as between overlapping symptoms and asthma, and moderate-to-severe asthma in particular.

They added that a subgroup analysis suggested that these associations were not the result of smoking or the age at which the patient was diagnosed with asthma. However, the genetic signals seemed to correlate with a predisposition to type 2 inflammation.

“Eosinophil count, atopy and asthma traits were prominent in phenome-wide analyzes of our top 8 signals, consistent with the important role of type 2 inflammation in [asthma-COPD overlap],” they said.

John and his colleagues said their report had some limitations. The sample size for the second phase was 4301 cases, so it was smaller and undernourished compared to the initial sample. They also said it was possible that some cases of asthma and COPD were misdiagnosed, although they made efforts to mitigate that possibility. Finally, their sample was predominantly European in descent.

Yet the authors said their analysis – the largest analysis of its kind to date – suggests an intermediate phenotype with features of asthma but also features of fixed airflow obstruction, “with pathways involving innate and adaptive immunity and potentially bone development, and signals for which the biology remains unclear.”


John C, Guyatt AL, Shrine N, et al. The genetic associations and architecture of asthma and chronic obstructive pulmonary disease overlap. Chest. Published online January 29, 2022. doi:10.1016/j.chest.2021.12.674


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