目的 使用两样本孟德尔随机化方法,探究吸烟行为与慢性肾衰竭及相关标志物间的因果关系。 方法 使用R语言及TwoSampleMR程序包作为分析工具,从多个数据库下载相关的大规模全基因组关联研究数据,提取其中单核苷酸多态性位点作为工具变量进行分析。主要使用逆方差加权法进行显著性分析及异质性检验,使用MR-Egger截距及MR-PRESSO法分析结果的水平多效性进行分析。使用漏斗图、留一法对结果进行潜在偏倚和稳健性确认。 结果 研究纳入工具变量有慢性肾衰竭22个、肾小球滤过率17个、尿白蛋白21个、尿微量白蛋白22个、血尿18个、胱抑素C 9个。逆方差加权法结果显示吸烟行为与慢性肾衰竭(OR=1.216,95% CI:1.051~1.408,P=0.009)、肾小球滤过率(OR=0.990,95% CI:0.984~0.996,P<0.001)、尿白蛋白(OR=1.051,95% CI:1.027~1.076,P<0.001)、尿微量白蛋白(OR=1.065,95% CI:1.021~1.110,P=0.003)、血尿(OR=1.002,95% CI:1.001~1.003,P=0.005)、胱抑素C(OR=1.050,95%CI:1.001~1.101,P=0.046)存在因果关系。结论 吸烟行为可导致慢性肾衰竭的发生及各项指标的恶化,是引发肾脏病的不良因素之一。
Objective This study aimed to use a two-sample Mendelian randomization approach to investigate the causal relationship between smoking behavior and chronic renal failure, along with related renal disease markers. Methods Using R Studio and packages such as TwoSampleMR for analysis, data from relevant large-scale genome-wide association studies were downloaded from public databases. Single nucleotide polymorphism sitess serving as instrumental variables were extracted for analysis. The results were mainly analyzed by Inverse variance weighted method for significance analysis and heterogeneity test, and the results were analyzed for horizontal multiplicity of results using MR-Egger intercept and MR-PRESSO methods. In addition, funnel plots and the leave-one-out method were used to confirm the potential bias and the robustness of the results. Results The instrumental variables included in the study were chronic renal failure (n=22), estimated glomerular filtration rate (n=17), urinary albumin (n=21), urinary microalbumin (n=22), haematuria (n=18), and cystatin C (n=9). The results of the inverse variance weighted method showed that smoking behavior was associated with chronic renal failure (OR=1.216, 95% CI: 1.051~1.408, P=0.009); lower estimated glomerular filtration rate (OR=0.990,95% CI: 0.984~0.996, P<0.001); higher albumin urine (OR=1.051, 95% CI: 1.027~1.076, P<0.001); higher microalbumin urine (OR=1.065, 95% CI: 1.021~1.110, P=0.003); haematuria (OR=1.002. 95% CI: 1.001~1.003, P=0.005); and higher cystatin C (OR=1.050, 95% CI:1.001~1.101, P=0.046) were causally related. Conclusion Smoking behavior leads to an increased risk of chronic renal failure and worsening of key renal function indicators, suggesting that smoking is a risk factors for renal disease. Smoking cessation can help prevent the development of kidney disease in smokers.