Abstract: 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 length.

Key words: Perinatal period, Smoking, Telomere length, Mendelian randomization, Risk prediction