血清 25-羟维生素 D 25(OH)对端粒磨损的影响：一项孟德尔随机化研究。

Impact of serum 25-hydroxyvitamin D 25(OH) on telomere attrition: A Mendelian Randomization study.

机构信息

Department of Biology and Biological Engineering, Food and Nutrition Science, Chalmers University of Technology, Gothenburg, Sweden.

Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK.

出版信息

Clin Nutr. 2020 Sep;39(9):2730-2733. doi: 10.1016/j.clnu.2019.12.008. Epub 2019 Dec 24.

DOI:10.1016/j.clnu.2019.12.008

PMID:31902602

Abstract

BACKGROUND

Conventional observational studies have suggested that 25-hydroxyvitamin D (25(OH)D) is inversely associated with telomere shortening. We aimed to apply two-sample Mendelian randomization (MR) to assess the causal association between serum 25(OH) D and telomere length (TL).

METHODS

MR was implemented by using summary-level data from the largest genome-wide association studies (GWAS) on vitamin D (n = 73 699) and TL (n = 37 684). Inverse variance weighted method (IVW) was used to estimate the causal estimates. Weighted median (WM)-based method, and MR-Egger, leave-one-out were applied as sensitivity analysis.

RESULTS

The results of MR demonstrated no effect of 25(OH)D on TL (IVW = β:-0.104, p = 0.219, WM = β:-0.109, p = 0.188; MR Egger = β:-0.127, p = 0.506). None of the 25(OH)D-related single nucleotide polymorphisms (SNPs) were significantly associated with TL. Heterogeneity tests did not detect heterogeneity. Furthermore, MR pleiotropy residual sum and outlier (MR-PRESSO) did not highlight any outliers (p = 0.424). Results of leave-one-out method demonstrated that the links are not driven because of the single SNPs.

CONCLUSIONS

Our study does not support any causal effect of 25(OH) D on TL.

摘要

背景

传统的观察性研究表明，25-羟维生素 D（25（OH）D）与端粒缩短呈负相关。我们旨在应用两样本 Mendelian 随机化（MR）来评估血清 25（OH）D 与端粒长度（TL）之间的因果关系。

方法

通过使用最大的维生素 D（n=73699）和 TL（n=37684）全基因组关联研究（GWAS）的汇总水平数据来实施 MR。逆方差加权法（IVW）用于估计因果估计值。加权中位数（WM）方法和 MR-Egger、逐一剔除法被用作敏感性分析。

结果

MR 的结果表明 25（OH）D 对 TL 没有影响（IVW：β：-0.104，p=0.219，WM：β：-0.109，p=0.188；MR-Egger：β：-0.127，p=0.506）。与 25（OH）D 相关的单核苷酸多态性（SNP）均与 TL 无显著相关性。异质性检验未发现异质性。此外，MR 多效性残差和异常值（MR-PRESSO）未突出任何异常值（p=0.424）。逐一剔除法的结果表明，这些关联不是由单个 SNP 驱动的。