DNA methylation-based biological age (DNAm age) is an important biomarker for adult health. Studies in specific age ranges have found widely varying results about its genetic and environmental causes of variation. However, these studies are not able to provide a comprehensive view of the causes of variation over the lifespan. In order to investigate the genetic and environmental causes of DNAm age variation across the lifespan, we pooled genome-wide DNA methylation data for 4217 people aged 0–92 years from 1871 families. DNAm age was calculated using the Horvath epigenetic clock. We estimated familial correlations in DNAm age for monozygotic (MZ) twin, dizygotic (DZ) twin, sibling, parent–offspring, and spouse pairs by cohabitation status. Genetic and environmental variance components models were fitted and compared. We found that twin pair correlations were − 0.12 to 0.18 around birth, not different from zero (all P > 0.29). For all pairs of relatives, their correlations increased with time spent living together (all P < 0.02) at different rates (MZ > DZ and siblings > parent–offspring; P < 0.001) and decreased with time spent living apart (P = 0.02) at similar rates. These correlation patterns were best explained by cohabitation-dependent shared environmental factors, the effects of which were 1.41 (95% confidence interval [CI] 1.16 to 1.66) times greater for MZ pairs than for DZ and sibling pairs, and the latter were 2.03 (95% CI 1.13 to 9.47) times greater than for parent–offspring pairs. Genetic factors explained 13% (95% CI − 10 to 35%) of variation (P = 0.27). Similar results were found for another two epigenetic clocks, suggesting that our observations are robust to how DNAm age is measured. In addition, results for the other clocks were consistent with there also being a role for prenatal environmental factors in determining their variation. Variation in DNAm age is mostly caused by environmental factors, including those shared to different extents by relatives while living together and whose effects persist into old age. The equal environment assumption of the classic twin study might not hold for epigenetic aging.

中文翻译：

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整个生命周期表观遗传衰老变异的遗传和环境原因

基于 DNA 甲基化的生物年龄（DNAm 年龄）是成人健康的重要生物标志物。对特定年龄范围的研究发现了其变异的遗传和环境原因的广泛不同的结果。然而，这些研究无法全面了解整个生命周期内的变异原因。为了研究 DNAm 在整个生命周期中年龄变化的遗传和环境原因，我们汇集了来自 1871 个家庭的 4217 名 0-92 岁人群的全基因组 DNA 甲基化数据。DNAm 年龄使用 Horvath 表观遗传时钟计算。我们根据同居状态估计了单卵 (MZ) 双胞胎、异卵 (DZ) 双胞胎、兄弟姐妹、父母-后代和配偶对 DNAm 年龄的家族相关性。对遗传和环境方差分量模型进行拟合和比较。我们发现双胞胎相关性在出生前后为 - 0.12 至 0.18，与零没有区别（所有 P > 0.29）。对于所有亲属，他们的相关性随着生活在一起的时间（所有 P < 0.02）以不同的比率增加（MZ > DZ 和兄弟姐妹 > 父母-后代；P < 0.001），并随着分开生活的时间而减少（P = 0.02）以类似的速度。这些相关模式最好用依赖同居的共享环境因素来解释，MZ 对的影响是 DZ 和兄弟对的 1.41（95% 置信区间 [CI] 1.16 到 1.66）倍，后者是 2.03（ 95% CI 1.13 到 9.47) 倍于亲代-后代对。遗传因素解释了 13%（95% CI - 10 至 35%）的变异（P = 0.27）。对另外两个表观遗传时钟也发现了类似的结果，表明我们的观察对于 DNAm 年龄的测量方式是可靠的。此外，其他时钟的结果与产前环境因素在决定它们的变化中也有作用是一致的。DNAm 年龄的变化主要是由环境因素引起的，包括那些共同生活的亲戚在不同程度上共享并持续到老年的环境因素。经典双胞胎研究的平等环境假设可能不适用于表观遗传衰老。包括亲属在同居期间不同程度地共享并影响持续到老年的那些。经典双胞胎研究的平等环境假设可能不适用于表观遗传衰老。包括亲属在同居期间不同程度地共享并影响持续到老年的那些。经典双胞胎研究的平等环境假设可能不适用于表观遗传衰老。