Genetic Risk and Chronic Obstructive Pulmonary Disease Independently Predict the Risk of Incident Severe COVID-19

Rationale: Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of preexisting COPD is unknown. Objectives: In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. Methods: We constructed a polygenic risk score for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. Results: Of 430,582 participants, 712 developed severe COVID-19 as of February 22, 2021, of whom 19.8% had preexisting COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.09-1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18-1.92) had higher risk of severe COVID-19 (P for trend = 0.001), and the association was independent of COPD (P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12-1.67; P = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35-3.04; P < 0.001) than those at low genetic risk and without COPD. Conclusions: The polygenic risk score, which combines multiple risk alleles, can be effectively used in screening for high-risk populations of severe COVID-19. High genetic risk correlates with a higher risk of severe COVID-19, regardless of preexisting COPD.