Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, 430030, P. R. China.
Electrophoresis. 2021 Aug;42(14-15):1488-1496. doi: 10.1002/elps.202000367. Epub 2021 Jun 10.
Age-related CpG (AR-CpG) sites are currently the most promising molecular markers for forensic age estimation. However, the AR-CpG sites of Han Chinese population remains to be systematically characterized. In this study, we performed genome-wide methylation analyses on 42 whole blood DNA from healthy Han Chinese volunteers (aged from 18 to 62 years) using the Illumina MethylationEPIC BeadChip microarray. As expected, both known and novel AR-CpG sites were identified. Considering the sex difference in aging rate, we then separately selected AR-CpG candidates and built pyrosequencing-based multiple linear regression models for age estimation of males and females. The model constructed from the male sample group (n = 167, aged from 1.50 to 85.71 years) explained 95.22% of variation in age using five AR-CpG sites (chr6:11044864 ELOVL2, chr1:207997068 C1orf132, cg19283806 CCDC102B, cg17740900, and chr10:73740306 CHST3) and yielded a mean absolute error (MAE) of 2.79 years. The model constructed from the female sample group (n = 141, aged from 3.33 to 80.38 years) explained 94.90% of variation in age with six AR-CpG sites (chr6:11044867 ELOVL2, chr1:207997060 C1orf132, chr2:106015757 FHL2, cg26947034, chr16: 67184108 B3GNT9, and chr20:44658203 SLC12A5) and yielded an MAE of 2.53 years. Besides, the estimated age was highly correlated with the actual age (R > 0.97). The robustness of these AR-CpG markers was demonstrated by 10-fold cross-validations. In conclusion, we updated the AR-CpG sites of Han Chinese population and provided two sets of AR-CpG sites for accurate age estimation.
年龄相关的 CpG（AR-CpG）位点是目前法医年龄推断最有前途的分子标志物。然而，汉族人群的 AR-CpG 位点仍有待系统地描述。在这项研究中，我们使用 Illumina MethylationEPIC BeadChip 微阵列对 42 份来自健康汉族志愿者的全血 DNA 进行了全基因组甲基化分析（年龄从 18 岁到 62 岁）。正如预期的那样，我们鉴定了已知和新的 AR-CpG 位点。考虑到衰老速度的性别差异，我们分别选择了 AR-CpG 候选者，并为男性和女性的年龄估计建立了焦磷酸测序的多元线性回归模型。从男性样本组（n=167，年龄从 1.50 岁到 85.71 岁）构建的模型使用五个 AR-CpG 位点（chr6:11044864 ELOVL2、chr1:207997068 C1orf132、cg19283806 CCDC102B、cg17740900 和 chr10:73740306 CHST3）解释了 95.22%的年龄变化，平均绝对误差（MAE）为 2.79 岁。从女性样本组（n=141，年龄从 3.33 岁到 80.38 岁）构建的模型使用六个 AR-CpG 位点（chr6:11044867 ELOVL2、chr1:207997060 C1orf132、chr2:106015757 FHL2、cg26947034、chr16:67184108 B3GNT9 和 chr20:44658203 SLC12A5）解释了 94.90%的年龄变化，平均绝对误差（MAE）为 2.53 岁。此外，估计的年龄与实际年龄高度相关（R>0.97）。通过 10 倍交叉验证证明了这些 AR-CpG 标记的稳健性。总之，我们更新了汉族人群的 AR-CpG 位点，并提供了两组 AR-CpG 位点用于准确的年龄估计。
