Age prediction of children and adolescents aged 6-17 years: an epigenome-wide analysis of DNA methylation

被引:28
作者
Li, Chunxiao [1 ]
Gao, Wenjing [1 ]
Gao, Ying [1 ]
Yu, Canqing [1 ]
Lv, Jun [1 ]
Lv, Ruoran [2 ]
Duan, Jiali [2 ]
Sun, Ying [2 ]
Guo, Xianghui [3 ]
Cao, Weihua [1 ]
Li, Liming [1 ]
机构
[1] Peking Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Beijing 100191, Peoples R China
[2] Beijing Ctr Dis Control & Prevent, Beijing 100013, Peoples R China
[3] Chaoyang Dist Ctr Dis Control & Prevent, Beijing 100021, Peoples R China
来源
AGING-US | 2018年 / 10卷 / 05期
基金
中国国家自然科学基金;
关键词
aging; DNA methylation; children; adolescent; prediction; Illumina Infinium MethylationEPIC Beadchip; EPIGENETIC DRIFT; GENE-EXPRESSION; CANCER-RISK; HETEROGENEITY; STABILITY; PACKAGE; MODELS; SITES; TWIN;
D O I
10.18632/aging.101445
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The DNA methylation age, a good reflection of human aging process, has been used to predict chronological age of adults and newborns. However, the prediction model for children and adolescents was absent. In this study, we aimed to generate a prediction model of chronological age for children and adolescents aged 6-17 years by using age-specific DNA methylation patterns from 180 Chinese twin individuals. We identified 6,350 age-related CpGs from the epigenome-wide association analysis (N=179). 116 known age-related sites in children were confirmed. 83 novel CpGs were selected as predictors from all age-related loci by elastic net regression and they could accurately predict the chronological age of the pediatric population, with a correlation of 0.99 and the error of 0.23 years in the training dataset (N=90). The predictive accuracy in the testing dataset (N=89) was high (correlation=0.93, error=0.62 years). Among the 83 predictors, 49 sites were novel probes not existing on the Illumina 450K BeadChip. The top two predictors of age were on the PRKCB and REG4 genes, which are associated with diabetes and cancer, respectively. Our results suggest that the chronological age can be accurately predicted among children and adolescents aged 6-17 years by 83 newly identified CpG sites.
引用
收藏
页码:1015 / 1026
页数:12
相关论文
共 47 条
[1]   Age-associated DNA methylation in pediatric populations [J].
Alisch, Reid S. ;
Barwick, Benjamin G. ;
Chopra, Pankaj ;
Myrick, Leila K. ;
Satten, Glen A. ;
Conneely, Karen N. ;
Warren, Stephen T. .
GENOME RESEARCH, 2012, 22 (04) :623-632
[2]   Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays [J].
Aryee, Martin J. ;
Jaffe, Andrew E. ;
Corrada-Bravo, Hector ;
Ladd-Acosta, Christine ;
Feinberg, Andrew P. ;
Hansen, Kasper D. ;
Irizarry, Rafael A. .
BIOINFORMATICS, 2014, 30 (10) :1363-1369
[3]   Epigenome-Wide Scans Identify Differentially Methylated Regions for Age and Age-Related Phenotypes in a Healthy Ageing Population [J].
Bell, Jordana T. ;
Tsai, Pei-Chien ;
Yang, Tsun-Po ;
Pidsley, Ruth ;
Nisbet, James ;
Glass, Daniel ;
Mangino, Massimo ;
Zhai, Guangju ;
Zhang, Feng ;
Valdes, Ana ;
Shin, So-Youn ;
Dempster, Emma L. ;
Murray, Robin M. ;
Grundberg, Elin ;
Hedman, Asa K. ;
Nica, Alexandra ;
Small, Kerrin S. ;
Dermitzakis, Emmanouil T. ;
McCarthy, Mark I. ;
Mill, Jonathan ;
Spector, Tim D. ;
Deloukas, Panos .
PLOS GENETICS, 2012, 8 (04) :189-200
[4]   Epigenetic regulation of ageing: linking environmental inputs to genomic stability [J].
Benayoun, Berenice A. ;
Pollina, Elizabeth A. ;
Brunet, Anne .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2015, 16 (10) :593-610
[5]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[6]   Perceptions of epigenetics [J].
Bird, Adrian .
NATURE, 2007, 447 (7143) :396-398
[7]   Epigenetic Predictor of Age [J].
Bocklandt, Sven ;
Lin, Wen ;
Sehl, Mary E. ;
Sanchez, Francisco J. ;
Sinsheimer, Janet S. ;
Horvath, Steve ;
Vilain, Eric .
PLOS ONE, 2011, 6 (06)
[8]   Regression models for twin studies: a critical review [J].
Carlin, JB ;
Gurrin, LC ;
Sterne, JAC ;
Morley, R ;
Dwyer, T .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2005, 34 (05) :1089-1099
[9]   DNA methylation-based measures of biological age: meta-analysis predicting time to death [J].
Chen, Brian H. ;
Marioni, Riccardo E. ;
Colicino, Elena ;
Peters, Marjolein J. ;
Ward-Caviness, Cavin K. ;
Tsai, Pei-Chien ;
Roetker, Nicholas S. ;
Just, Allan C. ;
Demerath, Ellen W. ;
Guan, Weihua ;
Bressler, Jan ;
Fornage, Myriam ;
Studenski, Stephanie ;
Vandiver, Amy R. ;
Moore, Ann Zenobia ;
Tanaka, Toshiko ;
Kiel, Douglas P. ;
Liang, Liming ;
Vokonas, Pantel ;
Schwartz, Joel ;
Lunetta, Kathryn L. ;
Murabito, Joanne M. ;
Bandinelli, Stefania ;
Hernandez, Dena G. ;
Melzer, David ;
Nalls, Michael ;
Pilling, Luke C. ;
Price, Timothy R. ;
Singleton, Andrew B. ;
Gieger, Christian ;
Holle, Rolf ;
Kretschmer, Anja ;
Kronenberg, Florian ;
Kunze, Sonja ;
Linseisen, Jakob ;
Meisinger, Christine ;
Rathmann, Wolfgang ;
Waldenberger, Melanie ;
Visscher, Peter M. ;
Shah, Sonia ;
Wray, Naomi R. ;
McRae, Allan F. ;
Franco, Oscar H. ;
Hofman, Albert ;
Uitterlinden, Andre G. ;
Absher, Devin ;
Assimes, Themistocles ;
Levine, Morgan E. ;
Lu, Ake T. ;
Tsao, Philip S. .
AGING-US, 2016, 8 (09) :1844-1865
[10]   Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response relationships [J].
Cortessis, Victoria K. ;
Thomas, Duncan C. ;
Levine, A. Joan ;
Breton, Carrie V. ;
Mack, Thomas M. ;
Siegmund, Kimberly D. ;
Haile, Robert W. ;
Laird, Peter W. .
HUMAN GENETICS, 2012, 131 (10) :1565-1589