Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Department of Genetic Identification, Erasmus University Medical Center, Rotterdam, the Netherlands.
Nat Commun. 2021 May 14;12(1):2830. doi: 10.1038/s41467-021-22752-6.
Coffee and tea are extensively consumed beverages worldwide which have received considerable attention regarding health. Intake of these beverages is consistently linked to, among others, reduced risk of diabetes and liver diseases; however, the mechanisms of action remain elusive. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. Here we report the results from epigenome-wide association studies (EWAS) on coffee and tea consumption in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis of coffee consumption reveals 11 CpGs surpassing the epigenome-wide significance threshold (P-value <1.1×10), which annotated to the AHRR, F2RL3, FLJ43663, HDAC4, GFI1 and PHGDH genes. Among them, cg14476101 is significantly associated with expression of the PHGDH and risk of fatty liver disease. Knockdown of PHGDH expression in liver cells shows a correlation with expression levels of genes associated with circulating lipids, suggesting a role of PHGDH in hepatic-lipid metabolism. EWAS meta-analysis on tea consumption reveals no significant association, only two CpGs annotated to CACNA1A and PRDM16 genes show suggestive association (P-value <5.0×10). These findings indicate that coffee-associated changes in DNA methylation levels may explain the mechanism of action of coffee consumption in conferring risk of diseases.
咖啡和茶是全球广泛饮用的饮料，其与健康的关系受到了相当多的关注。这些饮料的摄入与降低糖尿病和肝脏疾病的风险等因素有关；然而，其作用机制仍难以捉摸。表观遗传学被认为是一种介导饮食和生活方式因素对疾病发生影响的机制。在这里，我们报告了在来自 15 个队列的 15789 名欧洲和非裔美国人参与者中进行的咖啡和茶消耗的全基因组关联研究（EWAS）的结果。咖啡消耗的 EWAS 荟萃分析揭示了 11 个 CpG 超过了全基因组意义阈值（P 值<1.1×10），这些 CpG 注释到 AHRR、F2RL3、FLJ43663、HDAC4、GFI1 和 PHGDH 基因。其中，cg14476101 与 PHGDH 的表达和脂肪肝疾病的风险显著相关。肝细胞中 PHGDH 表达的敲低与与循环脂质相关的基因的表达水平相关，表明 PHGDH 在肝脂质代谢中起作用。对茶消耗的 EWAS 荟萃分析显示没有显著关联，只有两个注释到 CACNA1A 和 PRDM16 基因的 CpG 显示出提示性关联（P 值<5.0×10）。这些发现表明，咖啡相关的 DNA 甲基化水平变化可能解释了咖啡消耗对疾病风险的作用机制。
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