吸烟与C反应蛋白水平的因果关系:一项双样本孟德尔随机化研究
Causal relationship between smoking and level of C-reactive protein:a two-sample Mendelian randomization study
曾莹莹 1喻明兰 1王婷婷 1刘可智 1向波1
作者信息
- 1. 西南医科大学附属医院,四川 泸州 646000
- 折叠
摘要
背景 吸烟与C反应蛋白(CRP)有关,但既往研究结果可能受到混杂因素的影响,CRP在吸烟相关病理过程中的因果关系有待一步探究.目的 利用全基因组关联研究(GWAS)结果数据,探讨吸烟与CRP水平之间的因果关系,为制定相关公共健康政策和吸烟干预措施提供参考.方法 采用CRP以及开始定期吸烟的年龄、开始吸烟、戒烟、日吸烟量四种吸烟表型的GWAS结果数据,选择相互独立且与吸烟及CRP相关的遗传位点作为工具变量.应用逆方差加权法(IVW)及加权中位数法进行孟德尔随机化(MR)分析,对吸烟及CRP的双向因果关系进行探讨.采用Cochran's Q检验评估每个单核苷酸多态性(SNP)之间的异质性;采用MR多效性残差总和及异常值检测SNP异常值;采用MR-Egger截距测试检验SNP的水平多效性;采用留一法敏感性分析检验MR研究是否受单个SNP的影响.结果 CRP与开始吸烟之间存在双向因果关系(β=0.170,P=0.010)(开始吸烟是暴露因素)、(β=0.040,P=0.001)(CRP是暴露).结论 吸烟可能会导致CRP水平改变,而CRP水平改变也可能影响个体开始吸烟的倾向.
Abstract
Background Previous investigations have illuminated the correlation between smoking and C-reactive protein(CRP),but previous research findings may be influenced by other confounding factors.The causal relationship of CRP in smoking-related pathological process requires further exploration.Objective To investigate the causal relationship between smoking behavior and CRP by utilizing the cumulative statistical data from existing genome-wide association studies(GWAS),so as to provide references for formulating relevant public health policies and smoking intervention measures.Methods This research utilized the GWAS summary statistics for CRP and four smoking phenotypes:age of initiation of regular smoking,smoking initiation,smoking cessation and cigarettes per day-selecting independent genetic loci correlated with smoking and CRP as instrumental variables.The study employed the inverse variance weighted method(IVW)and the weighted median approach for two-sample Mendelian randomization(MR)analysis to explore the bidirectional causal relationship between smoking and CRP.The Cochran's Q test was applied to assess heterogeneity among single nucleotide polymorphisms(SNPs).MR pleiotropy residual sum and outlier was used to detect SNP outliers.MR-Egger intercept test examined the horizontal pleiotropy of SNPs.Leave-one-out sensitivity analysis assessed the impact of individual SNP on the Mendelian randomization results.Results The MR analysis revealed a bidirectional causal relationship between CRP and smoking initiation(β=0.170,P=0.01)(with smoking initiationas the exposure),(β=0.040,P=0.001)(with CRP as the exposure).Conclusion Smoking may lead to alterations in CRP levels,while changes in CRP levels could also influence individual's propensity to initiate smoking.
关键词
吸烟/C反应蛋白/全基因组关联研究/孟德尔随机化Key words
Smoking/C-reactive protein/Genome-wide association studies/Mendelian randomization引用本文复制引用
出版年
2024
国家科技期刊平台
NSTL
万方数据