Sex-specific DNA methylation in saliva from the multi-ethnic Future of Families and Child Wellbeing Study

Allison Reiner, Kelly M. Bakulski, Jonah D. Fisher, John F. Dou, Lisa Schneper, Colter Mitchell, Daniel A. Notterman, Matthew Zawistowski, Erin B. Ware

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number2222244
JournalEpigenetics
Volume18
Issue number1
DOIs
StatePublished - 2023

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

Keywords

  • AMDHD2
  • DNA methylation
  • autosomal chromosomes
  • epigenetic epidemiology
  • saliva
  • sex differences

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