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. 2022 Jul 14;12(1):12016.
doi: 10.1038/s41598-022-16350-9.

DNA methylation profile in beef cattle is influenced by additive genetics and age

André Mauric F Ribeiro  1 , Leticia P Sanglard  1 , Hiruni R Wijesena  1 , Daniel C Ciobanu  1 , Steve Horvath  2   3 , Matthew L Spangler  4
Affiliations

DNA methylation profile in beef cattle is influenced by additive genetics and age

André Mauric F Ribeiro et al. Sci Rep. .

Abstract

DNA methylation (DNAm) has been considered a promising indicator of biological age in mammals and could be useful to increase the accuracy of phenotypic prediction in livestock. The objectives of this study were to estimate the heritability and age effects of site-specific DNAm (DNAm level) and cumulative DNAm across all sites (DNAm load) in beef cattle. Blood samples were collected from cows ranging from 217 to 3,192 days (0.6 to 8.7 years) of age (n = 136). All animals were genotyped, and DNAm was obtained using the Infinium array HorvathMammalMethylChip40. Genetic parameters for DNAm were obtained from an animal model based on the genomic relationship matrix, including the fixed effects of age and breed composition. Heritability estimates of DNAm levels ranged from 0.18 to 0.72, with a similar average across all regions and chromosomes. Heritability estimate of DNAm load was 0.45. The average age effect on DNAm level varied among genomic regions. The DNAm level across the genome increased with age in the promoter and 5' UTR and decreased in the exonic, intronic, 3' UTR, and intergenic regions. In addition, DNAm level increased with age in regions enriched in CpG and decreased in regions deficient in CpG. Results suggest DNAm profiles are influenced by both genetics and the environmental effect of age in beef cattle.

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Conflict of interest statement

SH is a founder of the non-profit Epigenetic Clock Development Foundation which plans to license several patents from his employer UC Regents. The other authors declare no competing interests.

Figures

Figure 1
Figure 1
Exponential regression of mean DNAm level on distance of the methylated cytosines from CpG islands into bins of 1000 bp.
Figure 2
Figure 2
Density of heritability estimates of DNAm levels for each DNAm site (a) and heritability estimates of DNAm levels across all chromosomes (b).
Figure 3
Figure 3
Distribution of age effects on DNAm levels across all chromosomes. DNAm sites with significant age effect (P ≤ 10–25) are highlighted in green.
Figure 4
Figure 4
Exponential decay regression of Methylation load (DNAm load) on the age of animals (years).
Figure 5
Figure 5
Exponential regression of age effect on distance of the methylated cytosines from CpG islands into bins of 1000 bp.
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