Objective  To investigate the potential causal relationship between chronic rhinosinusitis (CRS) and chronic obstructive pulmonary disease (COPD) using a two-sample two-way Mendelian randomization (MR) approach. Methods  In the forward study, single nucleotide polymorphisms (SNPs) closely associated with CRS were selected as instrumental variables from publicly available genome-wide association studies datasets, with COPD as the outcome variable; conversely, in the reverse study, SNPs closely associated with COPD were selected as instrumental variables, with CRS as the outcome variable. MR analysis was conducted using three regression models: inverse variance weighted (IVW), MR-Egger regression analysis, and weighted median (WME) to assess the causal relationship between CRS and COPD. Cochran’s Q statistic, MR-Egger intercept, MR-PRESSO, and “leave-one-out” methods were employed to test for heterogeneity and horizontal pleiotropy, thereby evaluating the stability and reliability of the MR results. Results  A total of 14 SNPs closely associated with CRS were included in the forward study; the IVW-fixed effects analysis indicated that CRS may increase the risk of developing COPD [odds ratio=1.003, 95% confidence interval (1.002, 1.004), P<0.001], which was confirmed by the WME method, while the MR-Egger regression method did not show a causal link between CRS and COPD. Heterogeneity test (IVW result: Cochran’s Q=7.910, P=0.849; MR-Egger regression result: Cochran’s Q=7.450, P=0.827), MR-Egger intercept method (P=0.510), MR-PRESSO test (P=0.917), and “leave-one-out” method showed that the MR analysis results were reliable. In the reverse study, a total of 12 SNPs related to COPD were included as instrumental variables; MR analysis did not support the notion that COPD would increase the risk of CRS (P>0.05). Heterogeneity test (IVW result: Cochran’s Q=5.947, P=0.877; MR-Egger regression result: Cochran’s Q=5.937, P=0.821), MR-Egger intercept method (P=0.921), MR-PRESSO test (P=0.875), and “leave-one-out” analysis method showed that the MR analysis results were reliable. Conclusions  There is a potential causal association between CRS and COPD, and CRS may increase the risk of developing COPD. But there is no evidence to suggest that COPD increases the risk of CRS.

Citation： GUO Qingqing, NIU Dingren, ZHOU Ling. Chronic rhinosinusitis and chronic obstructive pulmonary disease: a two-sample two-way Mendelian randomization study. West China Medical Journal, 2024, 39(9): 1450-1456. doi: 10.7507/1002-0179.202311275 Copy