Genome‐wide identification of age‐related CpG sites for age estimation from blood DNA of Han Chinese individuals

Abstract 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.