Changes in DNA methylation from pre-to post-adolescence are associated with pubertal exposures

Luhang Han, Hongmei Zhang*, Akhilesh Kaushal, Faisal I. Rezwan, Latha Kadalayil, Wilfried Karmaus, A. John Henderson, Caroline L. Relton, Susan Ring, S. Hasan Arshad, Susan L. Ewart, John W. Holloway

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

1 Citation (Scopus)
71 Downloads (Pure)

Abstract

BACKGROUND: Adolescence is a period characterized by major biological development, which may be associated with changes in DNA methylation (DNA-M). However, it is unknown to what extent DNA-M varies from pre- to post-adolescence, whether the pattern of changes is different between females and males, and how adolescence-related factors are associated with changes in DNA-M.

METHODS: Genome-scale DNA-M at ages 10 and 18 years in whole blood of 325 subjects (n = 140 females) in the Isle of Wight (IOW) birth cohort was analyzed using Illumina Infinium arrays (450K and EPIC). Linear mixed models were used to examine DNA-M changes between pre- and post-adolescence and whether the changes were gender-specific. Adolescence-related factors and environmental exposure factors were assessed on their association with DNA-M changes. Replication of findings was attempted in the comparable Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.

RESULTS: In the IOW cohort, after controlling for technical variation and cell compositions at both pre- and post-adolescence, 15,532 cytosine-phosphate-guanine (CpG) sites (of 400,825 CpGs, 3.88%) showed statistically significant DNA-M changes from pre-adolescence to post-adolescence invariant to gender (false discovery rate (FDR) = 0.05). Of these 15,532 CpGs, 10,212 CpGs (66%) were replicated in the ALSPAC cohort. Pathway analysis using Ingenuity Pathway Analysis (IPA) identified significant biological pathways related to growth and development of the reproductive system, emphasizing the importance of this period of transition on epigenetic state of genes. In addition, in IOW, we identified 1179 CpGs with gender-specific DNA-M changes. In the IOW cohort, body mass index (BMI) at age 10 years, age of growth spurt, nonsteroidal drugs use, and current smoking status showed statistically significant associations with DNA-M changes at 15 CpGs on 14 genes such as the AHRR gene. For BMI at age 10 years, the association was gender-specific. Findings on current smoking status were replicated in the ALSPAC cohort.

CONCLUSION: Adolescent transition is associated with changes in DNA-M at more than 15K CpGs. Identified pathways emphasize the importance of this period of transition on epigenetic state of genes relevant to cell growth and immune system development.

Original languageEnglish
Article number176
JournalClinical Epigenetics
Volume11
Issue number1
DOIs
Publication statusPublished - 2 Dec 2019

Structured keywords

  • Bristol Population Health Science Institute

Keywords

  • Adolescence
  • ALSPAC
  • DNA methylation
  • Epigenetic
  • Gender
  • IOW
  • Puberty
  • Stability
  • Whole-genome

Fingerprint Dive into the research topics of 'Changes in DNA methylation from pre-to post-adolescence are associated with pubertal exposures'. Together they form a unique fingerprint.

  • Projects

    Cite this

    Han, L., Zhang, H., Kaushal, A., Rezwan, F. I., Kadalayil, L., Karmaus, W., Henderson, A. J., Relton, C. L., Ring, S., Arshad, S. H., Ewart, S. L., & Holloway, J. W. (2019). Changes in DNA methylation from pre-to post-adolescence are associated with pubertal exposures. Clinical Epigenetics, 11(1), [176]. https://doi.org/10.1186/s13148-019-0780-4