Causal association of obesity with epigenetic aging and telomere length: a bidirectional mendelian randomization study

作者：Jixin Li, Wenru Wang, Zhenyu Yang, Linjie Qiu, Yan Ren, Dongling Wang, Meijie Li, Wenjie Li, Feng Gao, Jin Zhang · 发表于：Lipids in Health and Disease · 年份：2024 · DOI：10.1186/s12944-024-02042-y · 被引用次数：24 · 研究领域：Telomeres, Telomerase, and Senescence、Epigenetics and DNA Methylation、Genetic Associations and Epidemiology

BACKGROUND: In observational studies, there exists an association between obesity and epigenetic age as well as telomere length. However, varying and partially conflicting outcomes have notably arisen from distinct studies on this topic. In the present study, two-way Mendelian randomization was used to identify potential causal associations between obesity and epigenetic age and telomeres. METHODS: A genome-wide association study was conducted using data from individuals of European ancestry to investigate bidirectional Mendelian randomization (MR) regarding the causal relationships between obesity, as indicated by three obesity indicators (body mass index or BMI, waist circumference adjusted for BMI or WCadjBMI, and waist-to-hip ratio adjusted for BMI or WHRadjBMI), and four epigenetic age measures (HannumAge, HorvathAge, GrimAge, PhenoAge), as well as telomere length. To assess these causal associations, various statistical methods were employed, including Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Weighted Mode, and Simple Mode. To address the issue of multiple testing, we applied the Bonferroni correction. These methods were used to determine whether there is a causal link between obesity and epigenetic age, as well as telomere length, and to explore potential bidirectional relationships. Forest plots and scatter plots were generated to show causal associations between exposures and outcomes. For a comprehensive visualization of the results, leave-one-out...