吸烟、围产期吸烟导致端粒长度变化的风险  

Risk of telomere length changes due to smoking,perinatal smoking

作　　者：夏晓晓 李伦兰 丁佩佩[1] 王婷 陈孟孟[1] XIA Xiaoxiao;LI Lunlan;DING Peipei;WANG Ting;CHEN Mengmeng(School of Nursing,Anhui Medical University,Hefei,Anhui 230032,China;Department of Human Resources,First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China)

机构地区：[1]安徽医科大学护理学院,安徽合肥230032 [2]安徽医科大学第一附属医院人力资源部,安徽合肥230022

出　　处：《职业与健康》2025年第3期328-335,共8页Occupation and Health

基　　金：安徽高校自然科学研究项目(KJ2020ZD18)。

摘　　要：目的采用2项两样本孟德尔随机化(Mendelian randomization,MR)探讨吸烟、围产期吸烟导致端粒长度变化的风险。方法将全基因组关联研究(genome-wideassociation study,GWAS)中吸烟(2018年)、围产期吸烟(2018年)的遗传数据作为工具变量分别与GWAS中端粒长度(2021年)的遗传数据进行两样本MR分析,主要采用逆方差加权法(inverse-variance weighted,IVW)进行分析,并以加权中位数法(weighted median estimator,WME)、基于Egger回归的孟德尔随机化(Mendelian randomization-egger regression,MR-Egger)等进行补充。根据比值比(odds ratio,OR)和95%CI评估相比于不吸烟者,吸烟、围产期吸烟导致端粒长度变化的风险,通过比较两者OR值推断相对于吸烟者,围产期吸烟导致端粒长度变化的风险。采用Cochran’s Q检验、MR-Egger截距法、MR-PRESSO、去一法进行敏感性分析。结果共筛选出35个与吸烟相关的单核苷酸多态性(single nucleotide polymorphism,SNP)和16个与围产期吸烟密切相关的SNP作为工具变量,IVW结果显示,相比于不吸烟者,吸烟、围产期吸烟导致端粒长度变短的风险约增加25%[OR=0.75(95%CI:0.66~0.85),P<0.05]和37%[OR=0.63(95%CI:0.52~0.76),P<0.05],相对于吸烟者来说,围产期吸烟导致端粒长度变短的风险可能有所增加,WME结果验证了此推测[OR=0.77(95%CI:0.67~0.89),P<0.05;OR=0.67(95%CI:0.53~0.85),P<0.05]。MR-Egger法和MR-PRESSO均未发现2项MR结果存在水平多效性(均P>0.05);Cochran’s Q结果均显示可能存在一定异质性(均P<0.05),但漏斗图均未发现显著异质性。结论遗传学预测,相比于不吸烟者,吸烟、围产期吸烟均与端粒长度变短的风险相关,相比于吸烟者,围产期吸烟更有可能导致端粒长度变短。Objective To explore the risk of telomere length changes due to smoking,perinatal smoking by two two-sample Mendelian randomization(MR).Methods The genetic data of smoking(2018)and perinatal smoking(2018)from the genome-wide association study(GWAS)were used as instrumental variables,and the genetic data of telomere length from the GWAS(2021)were used for two-sample MR analysis.The inverse variance weighting(IVW)method was used for the analysis,and the weighted median method(WME)and Mendelian randomization-egger(MR-Egger)regression method were used as supplements.The odds ratio(OR)and 95%CI were used to estimate the risk of telomere length change caused by smoking and perinatal smoking compared with non-smokers.The OR value was used to estimate the risk of telomere length change caused by perinatal smoking compared with smokers.The Cochran's Q test,MR-Egger intercept method,MR-PRESSO and leave-one-out method were used for sensitivity analysis.Results A total of 35 single nucleotide polymorphisms(SNP)associated with smoking and 16 SNP closely associated with perinatal smoking were screened as instrumental variables.The IVW results showed that compared with non-smokers,the risk of shorter telomere length was increased by 25%[OR=0.75(95%CI:0.66-0.85),P<0.05]and 37%[OR=0.63(95%CI:0.52-0.76),P<0.05]for smoking and perinatal smoking,respectively.Compared with smokers,perinatal smoking may increase the risk of shorter telomere length,and this speculation was verified by WME results[OR=0.77(95%CI:0.67-0.89),P<0.05;OR=0.67(95%CI:0.53-0.85),P<0.05].The MR-Egger method and MR-PRESSO did not find horizontal pleiotropy of the two MR results(both P>0.05).The Cochran's Q results showed that there may be some heterogeneity(all P<0.05),but the funnel plot did not find significant heterogeneity.Conclusion The genetic prediction shows that smoking and perinatal smoking are associated with the risk of shorter telomere length compared with non-smokers.Compared with smokers,perinatal smoking is more likely to lead to shorter telomere l

关 键 词：围产期 吸烟 端粒长度 孟德尔随机化 风险预测 

分 类 号：R394.6[医药卫生—医学遗传学]