Study Probes Genetic Links Between Asthma, COPD Overlap

A small proportion of patients have symptoms of both asthma and chronic obstructive pulmonary disease. A new report suggests there might 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 there is a spectrum of genetic influences that predispose some people to have symptoms of both conditions.

Asthma and COPD are 2 different diseases, but they share some features. In a new study published in Chest, corresponding author Catherine John of the University of Leicester, and colleagues explained that a subset of patients experience symptoms consistent with both asthma and COPD. Evidence suggests those patients end up with significantly worse outcomes than do patients with one disease or the other.

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 colleagues wanted to better understand the genetic architecture at play in the asthma-COPD overlap and figure out whether genetic risk factors for overlapping symptoms differ from risk factors for the individual diseases.

To do so, they conducted a genome-wide association study of 8068 people with asthma-COPD overlap and more than 40,000 controls without either asthma or COPD. After identifying promising genetic signals within a genetic database, they compared the asthma-COPD group with asthma-only controls and with COPD-only controls, in order to look for patterns and similarities.

The first phase of the research yielded 31 independent variables which the investigators determined were worthy of further examination. That examination led to the discovery of 8 novel signals they said were associated with asthma-COPD overlap.

“These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1),” John and colleagues wrote.

They further identified 1 intergenic signal, located on chromosome 5, that they said had not previously been associated with either condition, nor with lung function in general.

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

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

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

John and colleagues said there were some limitations to their report. The sample size for the second phase was 4301 cases, thus it was smaller and underpowered compared with the original sample. They also said it was possible some cases of asthma and COPD were mis-diagnosed, although they made efforts to mitigate that possibility. Lastly, their sample was predominantly European in ancestry.

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


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