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首页> 外文期刊>Human reproduction open. >Age at onset of different pubertal signs in boys and girls and differential DNA methylation at age 10 and 18?years: an epigenome-wide follow-up study
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Age at onset of different pubertal signs in boys and girls and differential DNA methylation at age 10 and 18?years: an epigenome-wide follow-up study

机译：男孩和女孩和女孩和女孩和差异DNA甲基化的不同青春期标志的年龄？年：几年：外观血杂种的后续研究

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STUDY QUESTION Is the age of onset of pubertal markers related to subsequent changes in DNA methylation (DNAm)? SUMMARY ANSWER We identified 273 cytosine-phosphate-guanine (CpG) dinucleotides in girls and 67 CpGs in boys that were related to puberty and that were replicable in two other investigations. WHAT IS KNOWN ALREADY Previously, 457 CpGs (not gender-specific) and 347 (in girls) and 50 (in boys), respectively, were found to be associated with puberty, according to investigations of studies from Denmark (20 girls and 31 boys) and North America (30 girls and 25 boys). STUDY DESIGN, SIZE, DURATION The study was based on a birth cohort of 1456 participants born in 1989/90, with follow-up at age 10 and 18?years. PARTICIPANTS/MATERIALS, SETTING, METHODS The follow-up included 470 participants with information on DNAm and age of pubertal onset (244 girls and 226 boys). Age of pubertal onset was ascertained retrospectively at age 18?years. Using the Pubertal Development Scale, both genders were asked about ages of onset of growth spurt, body hair growth and skin changes. Ages at voice deepening and growth of facial hair were inquired from boys; ages at breast development and menarche from girls. Blood samples were collected at 10 and 18?years of age. DNA was extracted using a standard salting out procedure. The methylation level for each CpG site was assessed using one of two different platforms. DNAm was measured by a ratio of intensities denoted as β values for each CpG site. After quality control, 349?455 CpG sites were available for analysis. M values were calculated (log2( β /(1? β )) to approximate a normal distribution, and their levels were adjusted for blood cell proportions. Linear mixed models were applied to test the association between age of pubertal markers and repeated measurement of DNAm at 10 and 18?years. MAIN RESULTS AND THE ROLE OF CHANCE In girls, a total of 63?019 CpGs statistically significantly changed after occurrence of any of the five pubertal events and 13?487 were changed subsequent to all five events: the respective number is boys were 3072 and 301. To further exclude false-positive findings, we investigated which CpGs were replicable in prior studies from Denmark or North America, resulting in 273 replicable CpG in girls and 67 CpGs in boys (236 and 68 genes, respectively). Most identified genes are known to be related to biological processes of puberty; however, genetic polymorphisms of only four of these genes were previously linked to pubertal markers in humans. LIMITATIONS, REASONS FOR CAUTION The relative age of pubertal onset to the age of DNAm measurements does not allow causal inference, since DNAm at an earlier age may have affected the pubertal age or pubertal age may have altered later DNAm. This investigation concentrates on autosomes. CpGs on X and Y chromosomes are not included in the current study. WIDER IMPLICATIONS OF THE FINDINGS Assessment of biological processes involved in pubertal transitions should include epigenetic information. Differential DNAm related to puberty needs to be investigated to determine whether it can act as an early marker for adult diseases known to be associated with puberty. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by NIH grants R03HD092776 (Epigenetic characterization of pubertal transitions) and R01AI121226. The 10-year follow-up of this study was funded by National Asthma Campaign, UK (Grant No 364), and the 18-year follow-up by a grant from the National Heart and Blood Institute (R01 HL082925). The authors have no conflicts to report.
机译：研究问题是与随后的DNA甲基化的变化（DNAM）发生的呕吐标志物的年龄？发明内容答案我们确定了273名磷酸磷酸胍（CPG）二核苷酸在女孩和67个与青春期相关的男孩中的CPG，在另外两项调查中可复制。据丹麦的研究（20个女孩和31名男孩20岁的调查）和北美（30名女孩和25个男孩）。研究设计，规模，持续时间研究基于1989/90年的1456名参与者的出生队列，随访于10岁和18岁。年。参与者/材料，设置，方法随访包括470名参与者，了解关于DNAM和青春期发作的年龄（244名女孩和226名男孩）。青春期衰老的年龄是在18岁时确定的追溯性。使用青春期发展规模，询问两年一代的生长刺激衰退，身体头发生长和皮肤变化。来自男孩的声音深化和面部头发的成长的年龄;乳房发育和女孩的初潮。收集在10岁和18岁的血液样品。使用标准盐洗方法提取DNA。使用两个不同平台中的一个评估每个CPG部位的甲基化水平。通过表示每个CPG部位的β值的强度比率测量Dnam。质量控制后，349？455个CPG网站可用于分析。计算m值（log2（β/（1β））以近似正常分布，调节其水平的血细胞比例。应用线性混合模型以测试青春期标记的年龄与Dnam的反复测量10年和18年。主要结果和机会在女孩的作用，共有63个？019 CPG在发生五个青春期事件中的任何一个和13岁以下发生后的任何五个事件后发生了统计学显着改变，所有五个事件发生在所有五个事件中：相应的数量是男孩是3072和301.为了进一步排除虚假阳性结果，我们调查了在丹麦或北美的事先研究中进行了复制的CPG，导致273个女孩在男孩和67名CPG中分别为67个CPG（236和68个基因） ）。已知最鉴定的基因与青春期的生物过程有关;然而，这些基因中只有四种的遗传多态性先前与人类的青春期标志物联系起来。限制，Cautio的原因ñ普国普国育龄至DNAG测量年龄的相对年龄不允许因果推断，因为较早年龄的DNAM可能影响了普腾的年龄或青春期年龄可能改变后来DNAM。该研究浓缩纯度染色物。 X和Y染色体上的CPG不包括在目前的研究中。研究结果对参与普国特转型的生物过程的研究结果更广泛地应包括表观遗传信息。需要调查与青春期相关的差异Dnam以确定它是否可以作为已知与青春期相关的成年疾病的早期标记。学习资金/竞争利益本工作得到了NIH授予R03HD092776（普别育转换的表观表征）和R01AI121226。本研究的10年后续行动由英国国家哮喘活动资助（授予364号），并由全国心脏和血液研究所获得的18年的后续行动（R01 HL082925）。提交人没有报告的冲突。

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