ObjectiveTo explore whether there is a causal relationship between intestinal flora and esophageal cancer. MethodsSummary statistics of intestinal flora and esophageal cancer were obtained from the genome-wide association studies (GWAS) database. Five methods, including inverse variance weighted (IVW), weighted median estimation, Mendelian randomization (MR)-Egger regression, single mode, and weighted mode, were used for analysis, with IVW as the main analysis method. Sensitivity analysis was used to evaluate the reliability of MR results. ResultsIn the IVW method, Oxalobacteraceae [OR=1.001, 95%CI (1.000, 1.002), P=0.023], Faecalibacterium [OR=1.001, 95%CI (1.000, 1.002), P=0.028], Senegalimassilia [OR=1.002, 95%CI (1.000, 1.003), P=0.006] and Veillonella [OR=1.001, 95%CI (1.000, 1.002), P=0.018] were positively correlated with esophageal cancer, while Burkholderiales [OR=0.999, 95%CI (0.998, 1.001), P=0.002], Eubacterium oxidoreducens [OR=0.998, 95%CI (0.997, 0.999), P=0.038], Romboutsia [OR=0.999, 95%CI (0.998, 1.000), P=0.048] and Turicibacter[OR=0.998, 95%CI (0.997, 0.999), P=0.013] were negatively correlated with esophageal cancer. Sensitivity analysis showed no evidence of heterogeneity, horizontal pleiotropy and reverse causality. ConclusionOxalobacteraceae, Faecalibacterium, Senegalimassilia and Veillonella increase the risk of esophageal cancer, while Burkholderiales, Eubacterium oxidoreducens, Romboutsia and Turicibacter decrease the risk of esophageal cancer. Further studies are needed to explore how these bacteria affect the progression of esophageal cancer.
ObjectiveTo investigate the causal relationship between gut microbiota and idiopathic pulmonary fibrosis (IPF). MethodsGenome-wide association studies (GWAS) data of gut microbiota and IPF were obtained from MiBioGen and Finngen databases, respectively. Instrumental variables were screened by means of significance, linkage disequilibrium, weak instrumental variable screening, and removal of confounding factors (genetics, smoking, host characteristics). Inverse variance weighted (IVW) was used as the main Mendelian randomization (MR) analysis method, and the weighted median, simple mode, MR-Egger, and weighted mode were used to perform MR to reveal the causal effect of gut microbiota and IPF. The Cochrane's Q, leave-one-out, MR-Egger-intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and Steiger tests were used to analyze the heterogeneity, horizontal pleiotropy, outliers, and directionality, respectively. ResultsIVW analysis results showed that Actinomycetes [OR=1.773, 95%CI (1.323, 2.377), P<0.001], Erysipelatoclostridium [OR=2.077, 95%CI (1.107, 3.896), P=0.023], and Streptococcus [OR=1.35, 95%CI (1.100, 1.657), P=0.004] could increase the risk of IPF. Bifidobacterium [OR=0.668, 95%CI (0.620, 0.720), P<0.001], Ruminococcus [OR=0.434, 95%CI (0.222,0.848), P=0.015], and Tyzzerella [OR=0.479, 95%CI (0.304, 0.755), P=0.001] could reduce the risk of IPF. No significant heterogeneity, horizontal pleiotropy, outliers, and reverse causality were found. ConclusionActinobacteria, Erysipelatoclostridium and Streptococcus may increase the risk of IPF, while Bifidobacterium, Ruminococcus and Tyzzerella may reduce the risk of IPF. Regulation of the above gut microbiota may become a new direction in the study of the pathogenesis of IPF.
Objective To analyze whether there is a causal association between psoriasis and Alzheimer disease (AD) by a two-sample two-way Mendelian randomization (MR) method. Methods In the forward study, the single nucleotide polymorphisms (SNPs) associated with psoriasis were obtained from the comprehensive statistical data of the genome-wide association study database as the instrumental variables, and AD as the outcome; in the reverse study, the SNPs associated with AD were taken as instrumental variables, and psoriasis as the outcome. Using two-sample two-way MR analysis, the odds ratio (OR) value and 95% confidence interval (CI) of regression models, namely inverse variance weighted (IVW) method, MR-Egger regression method, weighted median method, simple pattern method, and weighted pattern method, were used to evaluate the causal relationship between psoriasis and AD. Cochran’s Q test was used to assess the heterogeneity of genetic instrumental variables, MR-Egger intercept method was used to test the horizontal pleiotropy of the assessment, “leave-one-out” method was used to assess the sensitivity of a SNP to the effect of causality, and the symmetry of funnel plot was observed to assess bias. Results A total of 19 SNPs associated with psoriasis were included as instrumental variables in the forward study. The IVW analysis of the forward study showed that there was a causal correlation between psoriasis and AD [OR=1.032, 95%CI (1.014, 1.051), P<0.001], and MR-Egger regression method [OR=1.042, 95%CI (1.012, 1.073), P=0.013], weighted median [OR=1.048, 95%CI (1.023, 1.074), P<0.001], and weighted model [OR=1.046, 95%CI (1.020, 1.073), P=0.002] all supported this result. Heterogeneity test (IVW result: Q=13.752, P=0.745; MR-Egger regression result: Q=13.134, P=0.727), MR-Egger intercept method (Egger intercept=–0.004, P=0.442), the results of “leave-one-out” method and funnel plot showed that the results of MR analysis were reliable. A total of 127 AD-related SNPs were included as instrumental variables in the reverse study. In reverse research, there was no evidence to support the AD could increase the risk of psoriasis (P>0.05). Heterogeneity test (IVW result: Q=232.496, P<0.001; MR-Egger regression result: Q=232.119, P<0.001) suggested heterogeneity, but MR-Egger intercept method (Egger intercept=0.003, P=0.652), the results of “leave-one-out” method and funnel plot showed that the results of MR analysis were reliable. Conclusion There is a causal association between psoriasis and AD, and psoriasis may increase the risk of AD.
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.