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

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

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.

1868-7075
Han, Luhang
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Zhang, Hongmei
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Kaushal, Akhilesh
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Rezwan, Faisal I.
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Kadalayil, Latha
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Karmaus, Wilfried
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Henderson, A. John
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Relton, Caroline L.
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Ring, Susan
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Arshad, S. Hasan
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Ewart, Susan L.
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Holloway, John W.
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Han, Luhang
cfeafb0c-3b49-41ab-b05f-9cccf7573036
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Kaushal, Akhilesh
a7742b05-148f-411e-bd3d-c2c29ecdcfef
Rezwan, Faisal I.
203f8f38-1f5d-485b-ab11-c546b4276338
Kadalayil, Latha
e620b801-844a-45d9-acaf-e0a58acd7cf2
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Henderson, A. John
03d06941-3f2c-4a2e-998b-8d18124049d1
Relton, Caroline L.
dcf42a2b-b423-4675-806d-bc581afe17a7
Ring, Susan
79941daa-7ae8-47f1-beb4-e8560ce12fd8
Arshad, S. Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Ewart, Susan L.
48158071-d7b8-46b5-8aef-26ffb37eec3b
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a

Han, Luhang, Zhang, Hongmei, Kaushal, Akhilesh, Rezwan, Faisal I., Kadalayil, Latha, Karmaus, Wilfried, Henderson, A. John, Relton, Caroline L., Ring, Susan, Arshad, S. Hasan, Ewart, Susan L. and Holloway, John W. (2019) Changes in DNA methylation from pre- to post-adolescence are associated with pubertal exposures. Clinical Epigenetics, 11 (1), [176]. (doi:10.1186/s13148-019-0780-4).

Record type: Article

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.

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Accepted/In Press date: 15 November 2019
Published date: 2 December 2019

Identifiers

Local EPrints ID: 436404
URI: http://eprints.soton.ac.uk/id/eprint/436404
ISSN: 1868-7075
PURE UUID: fc201aa5-1a94-42e8-908d-afab8ac90367
ORCID for Faisal I. Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 10 Dec 2019 17:30
Last modified: 22 Nov 2021 03:04

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Contributors

Author: Luhang Han
Author: Hongmei Zhang
Author: Akhilesh Kaushal
Author: Faisal I. Rezwan ORCID iD
Author: Latha Kadalayil
Author: Wilfried Karmaus
Author: A. John Henderson
Author: Caroline L. Relton
Author: Susan Ring
Author: S. Hasan Arshad
Author: Susan L. Ewart

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