Li Shuai, Wong Ee Ming, Joo JiHoon E, Jung Chol-Hee, Chung Jessica, Apicella Carmel, Stone Jennifer, Dite Gillian S, Giles Graham G, Southey Melissa C, Hopper John L
Centre for Epidemiology and Biostatistics,Melbourne School of Population and Global Health,The University of Melbourne,Melbourne,Victoria,Australia.
Genetic Epidemiology Laboratory,Department of Pathology,The University of Melbourne,Melbourne,Victoria,Australia.
Twin Res Hum Genet. 2015 Dec;18(6):720-6. doi: 10.1017/thg.2015.75. Epub 2015 Nov 3.
The disease- and mortality-related difference between biological age based on DNA methylation and chronological age (Δage) has been found to have approximately 40% heritability by assuming that the familial correlation is only explained by additive genetic factors. We calculated two different Δage measures for 132 middle-aged female twin pairs (66 monozygotic and 66 dizygotic twin pairs) and their 215 sisters using DNA methylation data measured by the Infinium HumanMethylation450 BeadChip arrays. For each Δage measure, and their combined measure, we estimated the familial correlation for MZ, DZ and sibling pairs using the multivariate normal model for pedigree analysis. We also pooled our estimates with those from a former study to estimate weighted average correlations. For both Δage measures, there was familial correlation that varied across different types of relatives. No evidence of a difference was found between the MZ and DZ pair correlations, or between the DZ and sibling pair correlations. The only difference was between the MZ and sibling pair correlations (p < .01), and there was marginal evidence that the MZ pair correlation was greater than twice the sibling pair correlation (p < .08). For weighted average correlation, there was evidence that the MZ pair correlation was greater than the DZ pair correlation (p < .03), and marginally greater than twice the sibling pair correlation (p < .08). The varied familial correlation of Δage is not explained by additive genetic factors alone, implying the existence of shared non-genetic factors explaining variation in Δage for middle-aged women.
通过假设家族相关性仅由加性遗传因素解释，发现基于DNA甲基化的生物学年龄与实际年龄之间的疾病和死亡率相关差异（Δ年龄）具有约40%的遗传力。我们使用Infinium HumanMethylation450 BeadChip阵列测量的DNA甲基化数据，为132对中年女性双胞胎（66对同卵双胞胎和66对异卵双胞胎）及其215名姐妹计算了两种不同的Δ年龄测量值。对于每个Δ年龄测量值及其综合测量值，我们使用用于系谱分析的多元正态模型估计了同卵双胞胎、异卵双胞胎和兄弟姐妹对的家族相关性。我们还将我们的估计值与之前一项研究的估计值合并，以估计加权平均相关性。对于这两种Δ年龄测量值，不同类型亲属之间存在家族相关性差异。在同卵双胞胎和异卵双胞胎对的相关性之间，或异卵双胞胎和兄弟姐妹对的相关性之间，未发现差异证据。唯一的差异在于同卵双胞胎和兄弟姐妹对的相关性之间（p < 0.01），并且有边缘证据表明同卵双胞胎对的相关性大于兄弟姐妹对相关性的两倍（p < 0.08）。对于加权平均相关性，有证据表明同卵双胞胎对的相关性大于异卵双胞胎对的相关性（p < 0.03），并且略大于兄弟姐妹对相关性的两倍（p < 0.08）。Δ年龄的家族相关性差异不能仅由加性遗传因素解释，这意味着存在共同的非遗传因素解释中年女性Δ年龄的变异。
