Are shorter telomeres causal risk factors for facial aging on a large population level? To examine if longer, genetically predicted telomeres were causally associated with less facial aging using Mendelian randomization analysis. Two-sample Mendelian randomization methods were applied to the summary statistics of a genome-wide association study (GWAS) for self-reported facial aging from 417, 772 participants of the UK Biobank data. Twenty single-nucleotide polymorphisms (SNPs) that were of genome-wide significance were selected as instrumental variables for leukocyte telomere length. The main analyses were performed primarily using the random-effects inverse-variance weighted method and were complemented with the MR-Egger regression, weighted median, and weighted mode approaches. The intercept of MR-Egger regression was used to assess horizontal pleiotropy. Longer genetically predicted telomeres were associated with a lower likelihood of facial aging (β = − 0.02, 95% confidence interval: − 0.04, − 0.002). Comparable results were obtained using MR-Egger regression, weighted median, and weighted mode approaches. The intercept of MR-Egger regression was close to zero (0.002) that was not suggestive of horizontal pleiotropy. Our findings provided evidence to support a potential causal relationship between longer genetically predicted telomeres and less facial aging.

在大量人口水平上，较短的端粒是否是面部衰老的因果风险因素？为了检查更长的基因预测端粒是否与使用孟德尔随机化分析的较少面部衰老有因果关系。将两样本孟德尔随机化方法应用于全基因组关联研究 (GWAS) 的汇总统计数据，该研究针对来自英国生物银行数据的 417 名、772 名参与者的自我报告面部衰老。选择了 20 个具有全基因组意义的单核苷酸多态性 (SNP) 作为白细胞端粒长度的工具变量。主要分析主要使用随机效应逆方差加权方法进行，并辅以 MR-Egger 回归、加权中位数和加权模式方法。MR-Egger 回归的截距用于评估水平多效性。较长的基因预测端粒与较低的面部衰老可能性有关。β  = − 0.02, 95% 置信区间： − 0.04, − 0.002)。使用 MR-Egger 回归、加权中位数和加权模式方法获得了可比较的结果。MR-Egger 回归的截距接近于零 (0.002)，这并不暗示水平多效性。我们的研究结果提供了证据来支持更长的遗传预测端粒与更少的面部衰老之间的潜在因果关系。