青春期是一种高度遗传且可变的特征，环境因素在其最终时间和发展中发挥作用。青春期早发和晚发都与以后生活中发生的各种疾病有关，青春期时间和发育的表观遗传学特征可能会带来重要的见解。血液 DNA 甲基化对基因型和环境都有反应，与青春期有关。然而，此类研究相对较少。我们研究了 1539 名芬兰年轻双胞胎的外周血 DNA 甲基化谱（使用 Illumina 450 K 和 EPIC 平台），这些双胞胎与 12 岁和 14 岁的青春期发育量表 (PDS) 以及青春期年龄 (PA) 相关。固定效应荟萃分析两个平台在 347,521 个 CpG 上共同识别出 58 个与 PDS 或 PA 相关的 CpG 位点 (p < 1 × 10-5)。与 PA 相关的所有 4 个 CpG 和与 PDS 相关的 45 个 CpG 均具有性别特异性。 13 个 CpG 具有高遗传力（h2：0.51-0.98），而 1 个 CpG 位点（映射到 GET4）具有较高的共享环境成分，占该位点甲基化总体变异的 68%。利用双胞胎不一致分析，我们发现 6 个 CpG 位点（5 个与 PDS 相关，1 个与 PA 相关）与青春期有环境驱动的关联。此外，具有 PDS 或 PA 相关 CpG 的基因始终与各种发育过程和疾病（如乳腺癌、前列腺癌和卵巢癌）相关，而相关 CpG 位点的甲基化数量性状位点在青春期发育的免疫途径中丰富。相关的 DNA 甲基化位点并检查性别、环境和遗传学的影响，我们揭示了青春期背景下环境和遗传学之间复杂的相互作用。通过我们的全面分析，我们不仅加深了对遗传和环境因素在青春期及其时间的复杂过程中的重要性的理解，而且还深入了解了与疾病风险的潜在联系。© 2023。作者。

Puberty is a highly heritable and variable trait, with environmental factors having a role in its eventual timing and development. Early and late pubertal onset are both associated with various diseases developing later in life, and epigenetic characterisation of pubertal timing and development could lead to important insights. Blood DNA methylation, reacting to both genotype and environment, has been associated with puberty; however, such studies are relatively scarce. We investigated peripheral blood DNA methylation profiles (using Illumina 450 K and EPIC platforms) of 1539 young adult Finnish twins associated with pubertal development scale (PDS) at ages 12 and 14 as well as pubertal age (PA).Fixed effect meta-analysis of the two platforms on 347,521 CpGs in common identified 58 CpG sites associated (p < 1 × 10-5) with either PDS or PA. All four CpGs associated with PA and 45 CpGs associated with PDS were sex-specific. Thirteen CpGs had a high heritability (h2: 0.51-0.98), while one CpG site (mapped to GET4) had a high shared environmental component accounting for 68% of the overall variance in methylation at the site. Utilising twin discordance analysis, we found 6 CpG sites (5 associated with PDS and 1 with PA) that had an environmentally driven association with puberty. Furthermore, genes with PDS- or PA-associated CpGs were consistently linked to various developmental processes and diseases such as breast, prostate and ovarian cancer, while methylation quantitative trait loci of associated CpG sites were enriched in immune pathways developing during puberty.By identifying puberty-associated DNA methylation sites and examining the effects of sex, environment and genetics, we shed light on the intricate interplay between environment and genetics in the context of puberty. Through our comprehensive analysis, we not only deepen the understanding of the significance of both genetic and environmental factors in the complex processes of puberty and its timing, but also gain insights into potential links with disease risks.© 2023. The Author(s).