Identifying chronic obstructive pulmonary disease subtypes using multi-trait genetics

eBioMedicine

Andrey Ziyatdinov, Brian D. Hobbs, Samir Kanaan-Izquierdo, Matthew Moll, Phuwanat Sakornsakolpat, Nick Shrine, Jing Chen, Kijoung Song, Russell P. Bowler, Peter J. Castaldi, Martin D. Tobin, Peter Kraft, Edwin K. Silverman, Hanna Julienne, Michael H. Cho, Hugues Aschard 

Summary

Evidence before this study

Chronic Obstructive Pulmonary Disease (COPD) is a phenotypically heterogeneous disease that varies significantly in symptomatic and physiologic presentation. Many studies explored the biological basis for this heterogeneity through the classification of patients based on their molecular and phenotypic characteristics. However, this approach is severely hampered by the variability of phenotypes and biomarkers with time, treatment, and disease progression.

Added value of this study

This work investigates whether a genetically driven approach, based on shared genetics between phenotypes and biomarkers, can better inform the heterogeneity of obstructive lung diseases. By using germline genetic markers, which are present from birth and do not vary with time, our work addresses the existing limitation of biomarkers. Furthermore, the proposed approach takes advantage of the availability of genome-wide association study results from many human traits typically not available in a single cohort.

Implications of all the available evidence

Our study demonstrates that examining the shared genetics across phenotypes can help resolve some of the heterogeneity underlying obstructive lung diseases. We identified three distinct clusters of lung-associated variants displaying different associations with biologic and clinical phenotypes: one related to eosinophils and inflammatory biomarkers; a second related to lower body mass and greater emphysema; and a third with height. Overall, it suggests that genetic risk scores built out of these clusters of variants can help identifying patients that may benefit from more specific treatments.

More information at DOI: https://doi.org/10.1016/j.ebiom.2025.105609