Distinctions between sex and time in patterns of DNA methylation across puberty
Background: There are significant sex differences in human physiology and disease; the genomic sources of these differences, however, are not well understood. During puberty, a drastic neuroendocrine shift signals physical changes resulting in robust sex differences in human physiology. Here, we explore how shifting patterns of DNA methylation may inform these pathways of biological plasticity during the pubertal transition. In this study we analyzed DNA methylation (DNAm) in saliva at two time points across the pubertal transition within the same individuals. Our purpose was to compare two domains of DNAm patterns that may inform processes of sexual differentiation 1) sex related sites, which demonstrated differences between males from females and 2) time related sites in which DNAm shifted significantly between timepoints. We further explored the correlated network structure sex and time related DNAm networks and linked these patterns to pubertal stage, assays of salivary testosterone, a reliable diagnostic of free, unbound hormone that is available to act on target tissues, and overlap with androgen response elements.
Results: Sites that differed by biological sex were largely independent of sites that underwent change across puberty. Time-related DNAm sites, but not sex-related sites, formed correlated networks that were associated with pubertal stage. Both time and sex DNAm networks reflected salivary testosterone levels that were enriched for androgen response elements, with sex-related DNAm networks being informative of testosterone levels above and beyond biological sex later in the pubertal transition.
Conclusions: These results inform our understanding of the distinction between sex- and time-related differences in DNAm during the critical period of puberty and highlight a novel linkage between correlated patterns of sex-related DNAm and levels of salivary testosterone.
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Posted 26 May, 2020
On 19 May, 2020
On 11 May, 2020
Received 06 May, 2020
Received 14 Apr, 2020
On 13 Apr, 2020
On 12 Apr, 2020
Invitations sent on 12 Apr, 2020
On 12 Apr, 2020
On 11 Apr, 2020
On 11 Apr, 2020
On 09 Feb, 2020
Received 02 Feb, 2020
On 24 Jan, 2020
Received 08 Jan, 2020
On 24 Dec, 2019
Invitations sent on 23 Dec, 2019
On 27 Nov, 2019
On 26 Nov, 2019
On 26 Nov, 2019
On 25 Nov, 2019
Distinctions between sex and time in patterns of DNA methylation across puberty
Posted 26 May, 2020
On 19 May, 2020
On 11 May, 2020
Received 06 May, 2020
Received 14 Apr, 2020
On 13 Apr, 2020
On 12 Apr, 2020
Invitations sent on 12 Apr, 2020
On 12 Apr, 2020
On 11 Apr, 2020
On 11 Apr, 2020
On 09 Feb, 2020
Received 02 Feb, 2020
On 24 Jan, 2020
Received 08 Jan, 2020
On 24 Dec, 2019
Invitations sent on 23 Dec, 2019
On 27 Nov, 2019
On 26 Nov, 2019
On 26 Nov, 2019
On 25 Nov, 2019
Background: There are significant sex differences in human physiology and disease; the genomic sources of these differences, however, are not well understood. During puberty, a drastic neuroendocrine shift signals physical changes resulting in robust sex differences in human physiology. Here, we explore how shifting patterns of DNA methylation may inform these pathways of biological plasticity during the pubertal transition. In this study we analyzed DNA methylation (DNAm) in saliva at two time points across the pubertal transition within the same individuals. Our purpose was to compare two domains of DNAm patterns that may inform processes of sexual differentiation 1) sex related sites, which demonstrated differences between males from females and 2) time related sites in which DNAm shifted significantly between timepoints. We further explored the correlated network structure sex and time related DNAm networks and linked these patterns to pubertal stage, assays of salivary testosterone, a reliable diagnostic of free, unbound hormone that is available to act on target tissues, and overlap with androgen response elements.
Results: Sites that differed by biological sex were largely independent of sites that underwent change across puberty. Time-related DNAm sites, but not sex-related sites, formed correlated networks that were associated with pubertal stage. Both time and sex DNAm networks reflected salivary testosterone levels that were enriched for androgen response elements, with sex-related DNAm networks being informative of testosterone levels above and beyond biological sex later in the pubertal transition.
Conclusions: These results inform our understanding of the distinction between sex- and time-related differences in DNAm during the critical period of puberty and highlight a novel linkage between correlated patterns of sex-related DNAm and levels of salivary testosterone.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6