We analysed DNA methylation data from 30 datasets comprising 3474 individuals, 19 tissues and 8 ethnicities at CpGs covered by the Illumina450K array. We identified 4143 hypervariable CpGs (‘hvCpGs’) with methylation in the top 5% most variable sites across multiple tissues and ethnicities. hvCpG methylation was influenced but not determined by genetic variation, and was not linked to probe reliability, epigenetic drift, age, sex or cell heterogeneity effects. hvCpG methylation tended to covary across tissues derived from different germ-layers and hvCpGs were enriched for proximity to ERV1 and ERVK retrovirus elements. hvCpGs were also enriched for loci previously associated with periconceptional environment, parent-of-origin-specific methylation, and distinctive methylation signatures in monozygotic twins. Together, these properties position hvCpGs as strong candidates for studying how stochastic and/or environmentally influenced DNA methylation states which are established in the early embryo and maintained stably thereafter can influence life-long health and disease.

中文翻译：

---

组织和种族独立的高变 DNA 甲基化状态显示在早期人类胚胎中建立的证据

我们分析了来自 Illumina450K 阵列覆盖的 CpG 的 30 个数据集的 DNA 甲基化数据，这些数据集包括 3474 个个体、19 个组织和 8 个种族。我们鉴定了 4143 个高变 CpG ('hvCpG')，在多个组织和种族中，前 5% 的变异位点具有甲基化。hvCpG 甲基化受遗传变异影响但不受其决定，并且与探针可靠性、表观遗传漂移、年龄、性别或细胞异质性效应无关。hvCpG 甲基化倾向于在源自不同胚层的组织间共变，并且 hvCpG 因接近 ERV1 和 ERVK 逆转录病毒元件而富集。hvCpGs 还富集了先前与围孕期环境、亲本特异性甲基化和同卵双胞胎中独特的甲基化特征相关的基因座。一起，