Epigenome-wide association study (EWAS) on lipids: the Rotterdam Study.
Epigenome-wide association study (EWAS) on lipids: the Rotterdam Study.
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DOI：
10.1186/s13148-016-0304-4
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发表时间：
2017
影响因子：
5.7
通讯作者：
Dehghan A
中科院分区：
文献类型：
--
作者：
Braun KVE;Dhana K;de Vries PS;Voortman T;van Meurs JBJ;Uitterlinden AG;BIOS consortium;Hofman A;Hu FB;Franco OH;Dehghan A
DNA甲基化是一种关键的表观遗传机制，被认为与血脂水平相关。我们的目的是在鹿特丹研究（一项基于人群的队列研究）的725名参与者中确定DNA甲基化水平与甘油三酯、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）和总胆固醇血液水平相关的CpG位点。随后，我们在一个不重叠的760名参与者中寻求复制。使用Illumina Methylation 450阵列测量全血中的全基因组甲基化水平。使用线性混合效应模型检查脂质水平和DNA甲基化β值之间的关联。所有模型均根据性别、年龄、吸烟、白色血细胞比例、阵列编号和阵列位置进行调整。Bonferroni校正的p值低于1.08 × 10−7被认为具有统计学显著性。对DHCR 24、CPT 1A、ABCG 1和SREBF 1等基因的5个CpG位点进行了鉴定和复制。四个CpG位点与甘油三酯相关，包括注释为CPT 1A（cg 00574958和cg 17058475）、ABCG 1（cg 06500161）和SREBF 1（cg 11024682）的CpG位点。两个CpG位点与HDL-C相关，包括ABCG 1（cg 06500161）和DHCR 24（cg 17901584）。未观察到与LDL-C或总胆固醇的显著相关性。我们报告了HDL-C水平与DHCR 24附近CpG位点甲基化的相关性，DHCR 24是一种参与胆固醇生物合成的蛋白质编码基因，以前曾报道与其他代谢特征相关。此外，我们证实了先前报道的CPT 1A，ABCG 1和SREBF 1和脂质内CpG位点甲基化的相关性。这些结果提供了深入了解的机制，参与脂质代谢。本文的在线版本（doi：10.1186/s13148-016-0304-4）包含补充材料，可供授权用户使用。
DNA methylation is a key epigenetic mechanism that is suggested to be associated with blood lipid levels. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol in 725 participants of the Rotterdam Study, a population-based cohort study. Subsequently, we sought replication in a non-overlapping set of 760 participants. Genome-wide methylation levels were measured in whole blood using the Illumina Methylation 450 array. Associations between lipid levels and DNA methylation beta values were examined using linear mixed-effect models. All models were adjusted for sex, age, smoking, white blood cell proportions, array number, and position on array. A Bonferroni-corrected p value lower than 1.08 × 10−7 was considered statistically significant. Five CpG sites annotated to genes including DHCR24, CPT1A, ABCG1, and SREBF1 were identified and replicated. Four CpG sites were associated with triglycerides, including CpG sites annotated to CPT1A (cg00574958 and cg17058475), ABCG1 (cg06500161), and SREBF1 (cg11024682). Two CpG sites were associated with HDL-C, including ABCG1 (cg06500161) and DHCR24 (cg17901584). No significant associations were observed with LDL-C or total cholesterol. We report an association of HDL-C levels with methylation of a CpG site near DHCR24, a protein-coding gene involved in cholesterol biosynthesis, which has previously been reported to be associated with other metabolic traits. Furthermore, we confirmed previously reported associations of methylation of CpG sites within CPT1A, ABCG1, and SREBF1 and lipids. These results provide insight in the mechanisms that are involved in lipid metabolism. The online version of this article (doi:10.1186/s13148-016-0304-4) contains supplementary material, which is available to authorized users.