Growing evidence has linked inflammatory processes to cognitive decline and dementia. This work examines whether an epigenetic marker of C-reactive protein (CRP), a common clinical inflammatory biomarker, may mediate the relationship between educational attainment and cognition. We first evaluated whether 53 previously reported CRP-associated DNA methylation sites (CpGs) are associated with CRP, both individually and aggregated into a methylation risk score (MRSCRP), in 3 298 participants from the Health and Retirement Study (HRS, mean age = 69.7 years). Forty-nine CpGs (92%) were associated with the natural logarithm of CRP in HRS after adjusting for age, sex, smoking, BMI, genetic ancestry, and white blood cell counts (p < .05), and each standard deviation increase in MRSCRP was associated with a 0.38 unit increase in lnCRP (p = 4.02E-99). In cross-sectional analysis, for each standard deviation increase in MRSCRP, total memory score and total cognitive score decreased, on average, by 0.28 words and 0.43 items, respectively (p < .001). Further, MRSCRP mediated 6.9% of the relationship between high school education and total memory score in a model adjusting for age, sex, and genetic ancestry (p < .05); this was attenuated to 2.4% with additional adjustment for marital status, APOE ε4 status, health behaviors, and comorbidities (p < .05). Thus, CRP-associated methylation may partially mediate the relationship between education and cognition at older ages. Further research is warranted to determine whether DNA methylation at these sites may improve current prediction models for cognitive impairment in older adults.

中文翻译：

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C 反应蛋白相关 CpG 位点的 DNA 甲基化可能介导受教育程度和认知之间的途径


越来越多的证据表明炎症过程与认知能力下降和痴呆有关。这项工作检查了 C 反应蛋白 （CRP） 的表观遗传标志物（一种常见的临床炎症生物标志物）是否可能介导教育程度与认知之间的关系。我们首先评估了 53 个先前报道的 CRP 相关 DNA 甲基化位点 （CpGs） 是否与 CRP 相关，包括单独和汇总到甲基化风险评分 （MRSCRP） 中，来自健康与退休研究 （HRS，平均年龄 = 69.7 岁）。在调整年龄、性别、吸烟、BMI、遗传血统和白细胞计数后，49 个 CpG （92%） 与 HRS 中 CRP 的自然对数相关 （p < .05），MRSCRP 的每个标准差增加与 lnCRP 增加 0.38 个单位相关 （p = 4.02E-99）。在横断面分析中，对于 MRSCRP 的每个标准差增加，总记忆评分和总认知评分平均分别减少 0.28 个单词和 0.43 个项目 （p < .001）。此外，在调整年龄、性别和遗传血统的模型中，MRSCRP 介导了 6.9% 的高中教育与总记忆分数之间的关系 （p < .05）;通过对婚姻状况、 APOE ε4 状态、健康行为和合并症的额外调整，这一比例降低到 2.4% （p < .05）。因此，CRP 相关甲基化可能部分介导了老年教育与认知之间的关系。需要进一步的研究来确定这些位点的 DNA 甲基化是否可以改善当前老年人认知障碍的预测模型。