https://orcid.org/0000-0003-4731-8158
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ABSTRACT
The prevalence and severity of many diseases differs by sex, potentially due to sex-specific patterns in DNA methylation. Autosomal sex-specific differences in DNA methylation have been observed in cord blood and placental tissue but are not well studied in saliva or in diverse populations. We sought to characterize sex-specific DNA methylation on autosomal chromosomes in saliva samples from children in the Future of Families and Child Wellbeing Study, a multi-ethnic prospective birth cohort containing an oversampling of Black, Hispanic and low-income families. DNA methylation from saliva samples was analysed on 796 children (50.6% male) at both ages 9 and 15 with DNA methylation measured using the Illumina HumanMethylation 450k array. An epigenome-wide association analysis of the age 9 samples identified 8,430 sex-differentiated autosomal DNA methylation sites (P < 2.4 × 10−7), of which 76.2% had higher DNA methylation in female children. The strongest sex-difference was in the cg26921482 probe, in the AMDHD2 gene, with 30.6% higher DNA methylation in female compared to male children (P < 1 × 10−300). Treating the age 15 samples as an internal replication set, we observed highly consistent results between the ages 9 and 15 measurements, indicating stable and replicable sex-differentiation. Further, we directly compared our results to previously published DNA methylation sex differences in both cord blood and saliva and again found strong consistency. Our findings support widespread and robust sex-differential DNA methylation across age, human tissues, and populations. These findings help inform our understanding of potential biological processes contributing to sex differences in human physiology and disease.
Acronyms
| FFCWS | = | : Future of Families and Child Wellbeing Study |
| DNAm | = | : DNA methylation |
| EWAS | = | : Epigenome-wide association study |
| eFORGE | = | : experimentally-derived Functional element Overlap analysis of ReGions from EWAS |
Acknowledgments
We thank the participants and staff of the Future of Families and Child Wellbeing Study. We also wish to thank Brittni Delmaine for her editorial services.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/15592294.2023.2222244
Author contributions
Allison Reiner: software, visualization, formal analysis, data curation, writing-original draft
Matthew Zawistowski: conceptualization, methodology, writing-review & editing, supervision, funding acquisition
Kelly M. Bakulski: conceptualization, methodology, supervision, project administration, writing-review & editing, funding acquisition
Erin B. Ware: conceptualization, methodology, supervision, project administration, writing-review & editing, funding acquisition
Jonah D. Fisher: conceptualization, validation, data curationa
Colter Mitchell: validation, project administration, writing-review & editing
John F. Dou: validation, writing-review & editing
Lisa Schneper: investigation, writing-review & editing
Daniel A. Notterman: investigation, project administration, writing-review & editing.
Data availability statement
The data that support the findings of this study are available on request from the co-authors [DN, CM]. The data are not publicly available due to restrictions; however, data will be released in 2023 per the NIH data guidelines. Survey data for the Future of Families and Child Wellbeing study can be accessed at https://ffcws.princeton.edu/.