a Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health , University of Melbourne , Parkville , Victoria , Australia.
b Genetic Epidemiology Laboratory, Department of Pathology , University of Melbourne , Parkville , Victoria , Australia.
Epigenetics. 2017;12(11):973-981. doi: 10.1080/15592294.2017.1384891.
To address the limitations in current classic twin/family research on the genetic and/or environmental causes of human methylomic variation, we measured blood DNA methylation for 479 women (mean age 56 years) including 66 monozygotic (MZ), 66 dizygotic (DZ) twin pairs and 215 sisters of twins, and 11 random technical duplicates using the HumanMethylation450 array. For each methylation site, we estimated the correlation for pairs of duplicates, MZ twins, DZ twins, and siblings, fitted variance component models by assuming the variation is explained by genetic factors, by shared and individual environmental factors, and by independent measurement error, and assessed the best fitting model. We found that the average (standard deviation) correlations for duplicate, MZ, DZ, and sibling pairs were 0.10 (0.35), 0.07 (0.21), -0.01 (0.14) and -0.04 (0.07). At the genome-wide significance level of 10, 93.3% of sites had no familial correlation, and 5.6%, 0.1%, and 0.2% of sites were correlated for MZ, DZ, and sibling pairs. For 86.4%, 6.9%, and 7.1% of sites, the best fitting model included measurement error only, a genetic component, and at least one environmental component. For the 13.6% of sites influenced by genetic and/or environmental factors, the average proportion of variance explained by environmental factors was greater than that explained by genetic factors (0.41 vs. 0.37, P value <10). Our results are consistent with, for middle-aged woman, blood methylomic variation measured by the HumanMethylation450 array being largely explained by measurement error, and more influenced by environmental factors than by genetic factors.
为了解决当前经典双胞胎/家庭研究在人类甲基组变异的遗传和/或环境原因方面的局限性，我们对 479 名女性（平均年龄 56 岁）的血液 DNA 甲基化进行了测量，包括 66 对同卵（MZ）双胞胎、66 对异卵（DZ）双胞胎和 215 对双胞胎姐妹，以及 11 个随机技术重复使用 HumanMethylation450 阵列。对于每个甲基化位点，我们估计了重复对、MZ 双胞胎、DZ 双胞胎和兄弟姐妹的相关性，通过假设遗传因素、共同和个体环境因素以及独立测量误差来拟合方差成分模型，并评估了最佳拟合模型。我们发现，重复、MZ、DZ 和兄弟姐妹对的平均（标准差）相关性分别为 0.10（0.35）、0.07（0.21）、-0.01（0.14）和-0.04（0.07）。在全基因组显著水平为 10 时，93.3%的位点没有家族相关性，5.6%、0.1%和 0.2%的位点与 MZ、DZ 和兄弟姐妹对相关。对于 86.4%、6.9%和 7.1%的位点，最佳拟合模型仅包括测量误差、遗传成分和至少一个环境成分。对于 13.6%受遗传和/或环境因素影响的位点，环境因素解释的方差比例大于遗传因素（0.41 与 0.37，P 值 <10）。我们的结果与中年女性的血液甲基组变异一致，通过 HumanMethylation450 阵列测量的血液甲基组变异主要由测量误差解释，并且受环境因素的影响大于遗传因素。
