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

• Type of Material: Article
• Authors: Luhang Han, University of Memphis; Hongmei Zhang, University of Memphis; Akhilesh Kaushal, Emory University; Faisal I Rezwan, Cranfield University; Latha Kadalayil, University of Southampton, Faculty of Medicine; Wilfried Karmaus, University of Memphis; John A Henderson, Bristol Medical School; Caroline L Relton, Bristol Medical School; Susan Ring, Bristol Medical School; Hasan S Arshad, University of Southampton, Faculty of Medicine; Susan L Ewart, Michigan State University; John W Holloway, University of Southampton, Faculty of Medicine
• Language: English
• Date: 2019-12-02
• Publisher: Emory University Libraries
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s). 2019
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13148-019-0780-4
• Title of Journal or Parent Work: Clinical Epigenetics
• Volume: 11
• Issue: 1
• Start Page: 176
• End Page: 176
• Grant/Funding Information: The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf); Generation of methylation array data was specifically funded by NIH R01AI121226, R01AI091905, BBSRC BBI025751/1 and BB/I025263/1, MRC MC_UU_12013/1, MC_UU_12013/2, MC_UU_12013/8.; Dr. Akhilesh Kaushal was supported by the University of Memphis, and the work of all other authors study was supported by the National Institutes of Health research funds R01AI121226 (MPI: H Zhang and JW Holloway).
• Keywords: Adolescent; ALSPAC; Adolescence; Whole-genome; DNA methylation; IOW; Stability; Gender; Epigenesis, Genetic; Female; CpG Islands; Epigenetic; Body Mass Index; Child; Humans; Cohort Studies; Adolescent Development; Epigenomics; Sex Characteristics; DNA Methylation; Male; Puberty
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Medicine and Surgery

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- A nd 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- A nd 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.