ArticleRespiratory research2025
Genetic resilience to chronic obstructive pulmonary disease is a clinically distinct subtype in individuals with cigarette smoke exposure.
Article in Respiratory research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThere is substantial unexplained variability in the development of disease. A genetic risk score for COPD identifies individuals at markedly elevated risk of COPD; however, many high-genetic risk individuals do not develop disease. We sought to define genetic resilience in COPD by identifying and characterizing individuals who are resistant to their elevated genetic susceptibility.
methodsWe defined resilience to genetic risk (genetic resilience) as absence of airflow obstruction (FEV
resultsWe found that, after adjustment for covariates, genetically resilient individuals (n = 144) had better lung function (β = 35.9% predicted, p < 0.001), fewer symptoms, and less radiographic disease compared to genetic risk-matched individuals with COPD (n = 362). Conversely, when compared to clinically resilient individuals (n = 420), genetically resilient individuals had slightly lower lung function and slightly worse radiographic measures of disease. Both clinically and genetically resilient individuals had higher survival compared to genetic-risk matched cases (hazard ratios = 0.34 and 0.41 with p < 0.001 and p = 0.002, respectively). While the majority of genetically resilient individuals remained resilient across the 5-year and 10-year follow-up visits, a higher proportion of clinically resilient individuals remained resilient across the follow-up period. Non-Hispanic white genetically resilient individuals had higher social vulnerability across multiple measures compared to both clinically resilient individuals and genetic risk-matched individuals with COPD. DISCUSSION: Genetic resilience to COPD represents a unique subtype of smokers that is distinct from clinical resilience and has important disease-related differences from genetic risk-matched individuals with COPD. Future studies are needed to identify the underlying biological contributors to the multiple types of resilience in COPD.
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