Background

There is an important interplay between epigenetic factors and body weight, and previous work has identified ten sites where DNA methylation is robustly associated with body mass index (BMI) cross-sectionally. However, interpretation of the associations is complicated by the substantial changes in BMI often occurring in late-life, and the fact that methylation is often driven by genetic variation. This study therefore investigated the longitudinal association between these ten sites and BMI from midlife to late-life, and whether associations persist after controlling for genetic factors.

Methods

We used data from 535 individuals (mean age 68) in the Swedish Adoption/Twin Study of Aging (SATSA) with longitudinal measures of both DNA methylation from blood samples and BMI, spanning up to 20 years. Methylation levels were measured with the Infinium Human Methylation 450K or Infinium MethylationEpic array, with seven of the ten sites passing quality control. Latent growth curve models were applied to investigate longitudinal associations between methylation and BMI, and between–within models to study associations within twin pairs, thus adjusting for genetic factors.

Results

Baseline DNA methylation levels at five of the seven sites were associated with BMI level at age 65 (cg00574958 [CPT1A]; cg11024682 [SREBF1]), and/or change (cg06192883 [MYO5C]; cg06946797 [RMI2]; cg08857797 [VPS25]). For four of the five sites, the associations remained comparable within twin pairs. However, the effects of cg06192883 were substantially attenuated within pairs. No change in DNA methylation was detected for any of the seven evaluated sites.

Conclusion

Five of the seven sites investigated were associated with late-life level and/or change in BMI. The effects for four of the sites remained similar when examined within twin pairs, indicating that the associations are mainly environmentally driven. However, the substantial attenuation in the association between cg06192883 and late-life BMI within pairs points to the importance of genetic factors in this association.

中文翻译：

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在年长双胞胎的纵向样本中复制 DNA 甲基化与体重指数之间的关联。

背景

表观遗传因素和体重之间存在重要的相互作用，之前的工作已经确定了十个位点，其中 DNA 甲基化与横截面的体重指数 (BMI) 密切相关。然而，由于 BMI 在晚年经常发生的实质性变化，以及甲基化通常由遗传变异驱动的事实，对关联的解释变得复杂。因此，本研究调查了从中年到晚年这十个位点与 BMI 之间的纵向关联，以及在控制遗传因素后关联是否持续。

方法

我们在瑞典收养/双胞胎老龄化研究 (SATSA) 中使用了 535 名个体（平均年龄 68 岁）的数据，纵向测量了血液样本中的 DNA 甲基化和 BMI，时间跨度长达 20 年。使用 Infinium Human Methylation 450K 或 Infinium MethylationEpic 阵列测量甲基化水平，十个位点中有七个通过了质量控制。应用潜在生长曲线模型来研究甲基化和 BMI 之间的纵向关联，并应用模型之间的模型来研究双胞胎内的关联，从而调整遗传因素。

结果

七个位点中五个位点的基线 DNA 甲基化水平与 65 岁时的 BMI 水平相关（cg00574958 [ CPT1A ]；cg11024682 [ SREBF1 ]），和/或变化（cg06192883 [ MYO5C ]；cg06946797 ] 872778PS） . 对于五个站点中的四个站点，这种关联在双胞胎中仍然具有可比性。然而，cg06192883 的影响在成对内显着减弱。七个评估位点中的任何一个都未检测到 DNA 甲基化的变化。

结论

调查的七个地点中有五个与晚年水平和/或 BMI 的变化有关。在双胞胎中检查时，其中四个站点的影响仍然相似，表明这些关联主要是由环境驱动的。然而，cg06192883 与成对晚年 BMI 之间关联的显着减弱表明遗传因素在这种关联中的重要性。