Epigenome-Wide Association Study Identified VTI1A DNA Methylation Associated With Accelerometer-Assessed Physical Activity
Epigenome-Wide Association Study Identified VTI1A DNA Methylation Associated With Accelerometer-Assessed Physical Activity
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DOI：
10.1249/mss.0000000000002970
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发表时间：
2022-06
影响因子：
4.1
通讯作者：
Yuichiro Nishida;M. Hara;Hideki Ohmomo;Kanako Ono;A. Shimizu;Mikako Horita;C. Shimanoe;Naoto Taguchi;Y. Higaki;Keitaro Tanaka
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作者：
Yuichiro Nishida;M. Hara;Hideki Ohmomo;Kanako Ono;A. Shimizu;Mikako Horita;C. Shimanoe;Naoto Taguchi;Y. Higaki;Keitaro Tanaka
体育活动（PA）的健康益处可能是由DNA甲基化改变介导的。当前研究的目的是全面确定日本普通人群中甲基化水平与加速度计评估的总PA相关的CpG位点。方法研究对象来自佐贺日本多机构协作队列基线调查。通过单轴加速度计客观测量PA 7 d。我们采用两阶段策略。在发现阶段，我们对898个个体(随机样本（n = 507）和病例对照研究样本（n = 391）的总PA的两项全表观基因组关联研究进行了荟萃分析。使用Infinium EPIC或HM450阵列测量外周血DNA甲基化水平。在复制阶段，我们随后检查了CpG位点是否与总PA显著相关（P < 1 × 10−5），并在另一个样本（n = 1711）中复制，其中甲基化水平通过焦磷酸测序测量。采用多元线性回归来确定总PA和甲基化水平之间的横断面关联，并调整潜在混杂因素，包括体重指数。meta分析采用固定效应模型。还研究了总pa相关DNA甲基化与几种炎症标志物（如高敏c反应蛋白）之间的相关性。结果在meta分析中，9个CpG位点与总PA显著相关（P < 1 × 10−5）。9个位点中，成功复制了1个位点cg07030336（注释为VTI1A/ZDHHC6基因）（P = 0.009）。目前的研究表明，在一般人群中，加速度计评估的总PA越大，与c07030336 （VTI1A/ZDHHC6）的DNA甲基化水平越高相关。此外，我们发现cg07030336的甲基化水平与几种炎症生物标志物之间存在分歧关系。
ABSTRACT Introduction Health benefits of physical activity (PA) may be mediated by DNA methylation alterations. The purpose of the current study was to comprehensively identify CpG sites whose methylation levels were associated with accelerometer-assessed total PA in a general Japanese population. Methods The study participants were from the baseline survey of Saga Japan Multi-institutional Collaborative Cohort. PA was objectively measured by a single-axis accelerometer for 7 d. We used a two-stage strategy. In the discovery stage, we performed a meta-analysis of two epigenome-wide association studies of total PA in 898 individuals (a combination of random sample (n = 507) and case–control study sample (n = 391)). Peripheral blood DNA methylation levels were measured using Infinium EPIC or HM450 arrays. In the replication stage, we subsequently examined whether CpG sites significantly associated (P < 1 × 10−5) with total PA were replicated in another sample (n = 1711), in which methylation levels were measured by pyrosequencing. A multiple linear regression was performed to determine the cross-sectional association between total PA and methylation levels with adjustment for potential confounders, including body mass index. A fixed-effects model was used in the meta-analysis. Correlations between total PA–associated DNA methylation and several inflammatory markers, such as high-sensitivity C-reactive protein, were also conducted. Results In the meta-analysis, nine CpG sites were significantly associated with total PA (P < 1 × 10−5). Among the nine sites, one site cg07030336 (annotated to VTI1A/ZDHHC6 gene) was successfully replicated (P = 0.009). Conclusions The current study showed that greater accelerometer-assessed total PA was associated with higher DNA methylation levels at cg07030336 (VTI1A/ZDHHC6) in the general population. In addition, we found a divergent relationship between the methylation levels at cg07030336 and several inflammatory biomarkers.