AI Article Synopsis

  • Some individuals display characteristics of both asthma and COPD, leading to a condition known as asthma-COPD overlap, which yields worse health outcomes compared to having either condition alone.
  • The study aimed to explore the genetic factors behind asthma-COPD overlap and how these differ from those linked to asthma or COPD separately.
  • Researchers identified eight new genetic signals associated with asthma-COPD overlap, revealing a mix of genetic influences related to type 2 inflammation and potential long-term health impacts.

Article Abstract

Background: Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone.

Research Question: What is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma?

Study Design And Methods: We conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P < 5 × 10) that remained associated in analyses comparing (1) asthma-COPD overlap vs asthma-only control subjects, and (2) asthma-COPD overlap vs COPD-only control subjects. These variants were analyzed in 12 independent cohorts (stage 2).

Results: We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P < 5 × 10) for asthma-COPD overlap (meta-analysis of stage 1 and 2 studies). 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). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD, or lung function. Subgroup analyses suggested that associations at these eight signals were not driven by smoking or age at asthma diagnosis, and in phenome-wide scans, eosinophil counts, atopy, and asthma traits were prominent.

Interpretation: We identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131047PMC
http://dx.doi.org/10.1016/j.chest.2021.12.674DOI Listing

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