基于妇女健康倡议和双胞胎英国队列的饮食质量的全基因组关联研究。
Epigenome-wide association study of diet quality in the Women's Health Initiative and TwinsUK cohort.
机构信息
Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Nutrition and Health Sciences Program, Laney Graduate School, Emory University, Atlanta, GA, USA.
出版信息
Int J Epidemiol. 2021 May 17;50(2):675-684. doi: 10.1093/ije/dyaa215.
BACKGROUND
Diet quality is a risk factor for chronic disease and mortality. Differential DNA methylation across the epigenome has been associated with chronic disease risk. Whether diet quality is associated with differential methylation is unknown. This study assessed whether diet quality was associated with differential DNA methylation measured across 445 548 loci in the Women's Health Initiative (WHI) and the TwinsUK cohort.
DESIGN
The discovery cohort consisted of 4355 women from the WHI. The replication cohort consisted of 571 mono- and dizygotic twins from the TwinsUK cohort. DNA methylation was measured in whole blood using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). A meta-analysis, stratified by study cohort, was performed using generalized linear models that regressed methylation on AHEI-2010, adjusting for cell composition, chip number and location, study characteristics, principal components of genetic relatedness, age, smoking status, race/ethnicity and body mass index (BMI). Statistical significance was defined as a false discovery rate < 0.05. Significant sites were tested for replication in the TwinsUK cohort, with significant replication defined by P < 0.05 and a consistent direction.
RESULTS
Diet quality was significantly associated with differential DNA methylation at 428 cytosine-phosphate-guanine (CpG) sites in the discovery cohort. A total of 24 CpG sites were consistent with replication in the TwinsUK cohort, more than would be expected by chance (P = 2.7x10-4), with one site replicated in both the blood and adipose tissue (cg16379999 located in the body of SEL1L).
CONCLUSIONS
Diet quality was associated with methylation at 24 CpG sites, several of which have been associated with adiposity, inflammation and dysglycaemia. These findings may provide insight into pathways through which diet influences chronic disease.
背景
饮食质量是慢性病和死亡率的一个风险因素。整个表观基因组中不同的 DNA 甲基化与慢性病风险相关。饮食质量是否与差异甲基化有关尚不清楚。本研究评估了饮食质量是否与在 WHI 和 TwinsUK 队列中测量的 445548 个基因座的全基因组 DNA 甲基化差异相关。
设计
发现队列由来自 WHI 的 4355 名女性组成。复制队列由来自 TwinsUK 队列的 571 对单卵和双卵双胞胎组成。使用 Illumina Infinium HumanMethylation450 Beadchip 在全血中测量 DNA 甲基化。使用替代健康饮食指数 2010 版（AHEI-2010）评估饮食质量。使用广义线性模型对研究队列进行分层荟萃分析，该模型将甲基化回归到 AHEI-2010 上，调整细胞组成、芯片数量和位置、研究特征、遗传相关性的主要成分、年龄、吸烟状况、种族/民族和体重指数（BMI）。定义统计学意义为错误发现率 < 0.05。在 TwinsUK 队列中测试了显著位点的复制，显著复制的定义为 P < 0.05 和一致的方向。
结果
饮食质量与发现队列中 428 个胞嘧啶-磷酸-鸟嘌呤（CpG）位点的差异 DNA 甲基化显著相关。在 TwinsUK 队列中有 24 个 CpG 位点与复制一致，超过了随机预期的数量（P = 2.7x10-4），有一个位点在血液和脂肪组织中都有复制（位于 SEL1L 体中的 cg16379999）。
结论
饮食质量与 24 个 CpG 位点的甲基化相关，其中一些与肥胖、炎症和糖代谢紊乱有关。这些发现可能为饮食影响慢性病的途径提供了一些见解。
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