Background:DNA methylation patterns associated with habitual diet have not been well studied.Methods:Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality.Results:We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected P<1.6×10⁻³). Hypermethylation of cg18181703 (SOCS3) was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality (P=5.7×10⁻¹⁵). Ten additional diet-associated CpGs were nominally associated with all-cause mortality (P<0.05). MR analysis revealed 8 putatively causal associations for 6 CpGs with 4 cardiovascular disease risk factors (body mass index, triglycerides, high-density lipoprotein cholesterol concentrations, and type 2 diabetes mellitus; Bonferroni corrected MR P<4.5×10⁻⁴). For example, hypermethylation of cg11250194 (FADS2) was associated with lower triglyceride concentrations (MR, P=1.5×10⁻¹⁴).and hypermethylation of cg02079413 (SNORA54; NAP1L4) was associated with body mass index (corrected MR, P=1×10⁻⁶).Conclusions:Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.

中文翻译：

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饮食的全血 DNA 甲基化特征与心血管疾病危险因素和全因死亡率相关。


背景：与习惯饮食相关的 DNA 甲基化模式尚未得到充分研究。方法：使用地中海式饮食评分和替代健康饮食指数评分来表征饮食质量。我们对 5 个基于人群的队列（包括 6662 名欧洲血统、2702 名非洲血统和360 名西班牙裔参与者。对于全表观基因组分析中确定的与饮食相关的 CpG，我们进行了孟德尔随机化 (MR) 分析，以检查它们与心血管疾病危险因素的关系，并检查了它们与全因死亡率的纵向关联。结果：我们确定了 30 个与地中海饮食相关的 CpG欧洲血统参与者的饮食风格评分或替代健康饮食指数，或两者兼而有之。在这些CpG中，12个CpG与全因死亡率显着相关（Bonferroni校正的P <1.6×10 ^-3 ）。 cg18181703 ( SOCS3 ) 的高甲基化与地中海式饮食评分和替代健康饮食指数得分较高以及全因死亡率风险较低相关( P =5.7×10 ^-15 )。另外十个与饮食相关的 CpG 名义上与全因死亡率相关 ( P <0.05)。 MR分析揭示了6个CpG与4个心血管疾病危险因素（体重指数、甘油三酯、高密度脂蛋白胆固醇浓度和2型糖尿病）的8个推定因果关系；Bonferroni校正了MR P <4.5×10 ^-4 ）。 例如，cg11250194（ FADS2 ）的高甲基化与较低的甘油三酯浓度相关（MR， P =1.5×10 ^-14 ）。cg02079413（ SNORA54 ； NAP1L4 ）的高甲基化与体重指数相关（校正的MR， P =1× 10 ^-6 ). 结论：在欧洲血统个体中，习惯性饮食质量与30个CpG的外周白细胞DNA甲基化水平差异相关，其中大多数还与多种健康结果相关。这些发现表明，饮食信息的综合基因组分析可能揭示疾病预防和治疗的分子靶标。