The effect of age on DNA methylation in whole blood among Bangladeshi men and women

BMC Genomics

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[1] 0000 0001 2175 0319, grid.185648.6, Divison of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL, USA;0000 0001 2293 4611, grid.261055.5, Department of Public Health, North Dakota State University, Fargo, ND, USA;0000 0001 2293 4611, grid.261055.5, Genomics and Bioinformatics Program, North Dakota State University, Fargo, ND, USA;0000 0001 2293 4611, grid.261055.5, Biostatistics Core Facility, North Dakota State University, Fargo, ND, USA;0000 0004 0600 7174, grid.414142.6, International Centre for Diarrhoeal Disease Research Bangladesh, 1000, Dhaka, Bangladesh;0000 0004 1936 7822, grid.170205.1, Department of Public Health Sciences, University of Chicago, 5841 S. Maryland Ave., W264, MC2000, 60637, Chicago, IL, USA;0000 0004 1936 7822, grid.170205.1, Department of Public Health Sciences, University of Chicago, 5841 S. Maryland Ave., W264, MC2000, 60637, Chicago, IL, USA;0000 0004 1936 7822, grid.170205.1, Department of Human Genetics and Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA;0000 0004 1936 7822, grid.170205.1, Department of Public Health Sciences, University of Chicago, 5841 S. Maryland Ave., W264, MC2000, 60637, Chicago, IL, USA;0000 0004 1936 7822, grid.170205.1, Department of Medicine, The University of Chicago, Chicago, IL, USA;0000 0004 1936 7822, grid.170205.1, Department of Human Genetics and Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA;Department of Epidemiology, Gillings School of Global Public Health, University of North Caroline, Chapel Hill, NC, USA;grid.452875.9, UChicago Research Bangladesh Mohakhali, 1230, Dhaka, Bangladesh;grid.452875.9, UChicago Research Bangladesh Mohakhali, 1230, Dhaka, Bangladesh;Research and Evaluation Division BRAC, Mohakhali, 1212, Dhaka, Bangladesh;

关键词: Genome-wide;    Age-associated;    Methylation;    Sex-specific;    Cell type adjustment;    RefFreeEWAS;    Age prediction model;   

DOI  :  10.1186/s12864-019-6039-9

来源: publisher

【 摘 要 】

BackgroundIt is well-known that methylation changes occur as humans age, however, understanding how age-related changes in DNA methylation vary by sex is lacking. In this study, we characterize the effect of age on DNA methylation in a sex-specific manner and determine if these effects vary by genomic context. We used the Illumina HumanMethylation 450 K array and DNA derived from whole blood for 400 adult participants (189 males and 211 females) from Bangladesh to identify age-associated CpG sites and regions and characterize the location of these age-associated sites with respect to CpG islands (vs. shore, shelf, or open sea) and gene regions (vs. intergenic). We conducted a genome-wide search for age-associated CpG sites (among 423,604 sites) using a reference-free approach to adjust for cell type composition (the R package RefFreeEWAS) and performed an independent replication analysis of age-associated CpGs.ResultsThe number of age-associated CpGs (p < 5 x 10− 8) were 986 among men and 3479 among women of which 2027(63.8%) and 572 (64.1%) replicated (using Bonferroni adjusted p < 1.2 × 10− 5). For both sexes, age-associated CpG sites were more likely to be hyper-methylated with increasing age (compared to hypo-methylated) and were enriched in CpG islands and promoter regions compared with other locations and all CpGs on the array. Although we observed strong correlation between chronological age and previously-developed epigenetic age models (r ≈ 0.8), among our top (based on lowest p-value) age-associated CpG sites only 12 for males and 44 for females are included in these prediction models, and the median chronological age compared to predicted age was 44 vs. 51.7 in males and 45 vs. 52.1 in females.ConclusionsOur results describe genome-wide features of age-related changes in DNA methylation. The observed associations between age and methylation were generally consistent for both sexes, although the associations tended to be stronger among women. Our population may have unique age-related methylation changes that are not captured in the established methylation-based age prediction model we used, which was developed to be non-tissue-specific.

【 授权许可】

CC BY