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对六种代谢特征的全甲基组研究
Hannah M Smith1, Hong Kiat Ng2, Joanna E Moodie3
1Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
medRxiv : the preprint server for health sciences
|June 10, 2024
概括
全表观基因组相关性研究确定了与代谢健康相关的DNA甲基化模式. 这些代谢特征的表观遗传分数 (EpiScores) 适用于祖先,并显示与认知功能的关联.
科学领域:
- 遗传学和表观遗传学
- 代谢健康研究 代谢健康研究
- 计算生物学 计算生物学
背景情况:
- 了解代谢健康的分子基础对于识别共享和独特的生物途径至关重要.
- 代谢特征如BMI,体脂百分比,WHR,葡萄糖,HDL胆固醇和总胆固醇是健康的关键指标.
研究的目的:
- 通过使用DNA甲基化数据,对六种代谢特征进行全表观基因组关联研究 (EWAS).
- 开发和验证各种祖先的代谢特征的表观遗传分数 (EpiScores).
- 调查代谢EpiScores和一般认知功能之间的关联.
主要方法:
- 全表观基因组关联研究 (EWAS) 在>750,000个CpG位点进行,其中包括来自苏格兰世代 (GS) 队列的>17,000名个人.
- 使用线性回归和贝叶斯式EWAS方法来确定与代谢特征相关的显著CpG位点.
- 使用弹性净惩罚回归来训练代谢EpiScores,然后在独立的队列中进行测试 (LBC1936和HELIOS).
主要成果:
- 每个特征确定了数千个显著的CpG,在最初的EWAS中,所有六个特征都与37个CpG相关.
- 贝叶斯式EWAS确定了3-27个CPG,其特征具有较高的后部包含概率.
- 代谢性EpiScores解释了马来族祖先亚组中高达27.1%的BMI变异,并且与欧洲祖先个体的认知功能有关.
结论:
- 代谢健康的表观遗传特征可以通过EWAS识别,并可以通过预测EpiScores进行总结.
- 代谢性EpiScores证明了跨祖先的适用性,并有可能反映大脑健康的差异.
- 这些发现凸显了DNA甲基化在代谢健康中的作用及其与不同人群认知功能的潜在联系.
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