Changes in DNA methylation from pre- to post-adolescence are associated with pubertal exposures.
ALSPAC
Adolescence
DNA methylation
Epigenetic
Gender
IOW
Puberty
Stability
Whole-genome
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
02 12 2019
02 12 2019
Historique:
received:
17
04
2019
accepted:
15
11
2019
entrez:
4
12
2019
pubmed:
4
12
2019
medline:
25
7
2020
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31791392
doi: 10.1186/s13148-019-0780-4
pii: 10.1186/s13148-019-0780-4
pmc: PMC6888960
doi:
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
176Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBI025751/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19009
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/I025263/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12013/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI121226
Pays : United States
Organisme : Wellcome Trust
ID : 102215/2/13/2
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI091905
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12013/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12013/8
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom
Références
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Clin Epigenetics. 2015 Oct 16;7:113
pubmed: 26478754
Int J Epidemiol. 2015 Aug;44(4):1181-90
pubmed: 25991711
J Allergy Clin Immunol. 1992 Aug;90(2):235-41
pubmed: 1500628
BMC Bioinformatics. 2012 May 08;13:86
pubmed: 22568884
PLoS One. 2016 Dec 9;11(12):e0166486
pubmed: 27935972
Bioinformatics. 2014 May 15;30(10):1363-9
pubmed: 24478339
Hum Genet. 2013 Oct;132(10):1077-130
pubmed: 23820649
Anticancer Res. 2018 Apr;38(4):2295-2302
pubmed: 29599352
EMBO Rep. 2012 Apr 10;13(5):423-30
pubmed: 22491032
Adv Exp Med Biol. 2007;612:34-48
pubmed: 18161480
Eur J Endocrinol. 2004 Nov;151 Suppl 3:U119-23
pubmed: 15554896
J Eur Acad Dermatol Venereol. 2013 Mar;27(3):e420-3
pubmed: 23003573
Genome Biol. 2014 Dec 03;15(12):522
pubmed: 25517766
Oncotarget. 2012 Apr;3(4):462-74
pubmed: 22577155
Int J Mol Epidemiol Genet. 2013 Jun 25;4(2):86-100
pubmed: 23875062
Int J Epidemiol. 2018 Aug 1;47(4):1043-1044i
pubmed: 29547889
Thorax. 1992 Jul;47(7):537-42
pubmed: 1412098
Nucleic Acids Res. 1988 Feb 11;16(3):1215
pubmed: 3344216
Hum Mol Genet. 2014 May 1;23(9):2290-7
pubmed: 24334605
Postepy Dermatol Alergol. 2014 Aug;31(4):256-61
pubmed: 25254011
Am Rev Respir Dis. 1992 Oct;146(4):888-94
pubmed: 1416415
Trends Immunol. 2006 Sep;27(9):399-404
pubmed: 16843067
Am J Physiol Endocrinol Metab. 2008 Aug;295(2):E278-86
pubmed: 18492777
PLoS One. 2012;7(10):e46705
pubmed: 23071618
BMC Bioinformatics. 2017 Apr 14;18(1):216
pubmed: 28410574
Arch Dis Child. 1986 Nov;61(11):1049-55
pubmed: 3098185
BMJ. 1991 Jul 20;303(6795):163-5
pubmed: 1878641
Int J Epidemiol. 2013 Feb;42(1):111-27
pubmed: 22507743
Bioinformatics. 2014 Feb 15;30(4):523-30
pubmed: 24336805
Clin Epigenetics. 2014 Sep 19;6(1):17
pubmed: 25250096
Epigenetics. 2014 Oct;9(10):1382-96
pubmed: 25424692
PLoS Med. 2017 Jan 17;14(1):e1002215
pubmed: 28095459
Am J Respir Crit Care Med. 2000 Jul;162(1):68-74
pubmed: 10903222
Int Immunopharmacol. 2002 Jul;2(8):1195-204
pubmed: 12349956
Nature. 2017 Jan 5;541(7635):81-86
pubmed: 28002404
J Allergy Clin Immunol. 2002 Apr;109(4):592-602
pubmed: 11941304
Int J Epidemiol. 2013 Feb;42(1):97-110
pubmed: 22507742
Nucleic Acids Res. 2013 Apr;41(7):e90
pubmed: 23476028
FASEB J. 2010 Sep;24(9):3135-44
pubmed: 20385621
Genome Res. 2010 Mar;20(3):332-40
pubmed: 20107151
Biochim Biophys Acta. 1973 Mar 28;299(3):397-403
pubmed: 4735514
Genome Biol. 2004;5(10):R80
pubmed: 15461798
Mini Rev Med Chem. 2002 Aug;2(4):361-72
pubmed: 12370057
J Immunol. 2006 Sep 15;177(6):4064-71
pubmed: 16951370
Genome Biol. 2015 Feb 15;16:37
pubmed: 25853392
Science. 2005 Jun 10;308(5728):1592-4
pubmed: 15947178
BMC Bioinformatics. 2010 Nov 30;11:587
pubmed: 21118553
Stem Cell Res Ther. 2019 Jan 15;10(1):26
pubmed: 30646953
Clin Epigenetics. 2013 Jan 03;5(1):1
pubmed: 23286427
Clin Epigenetics. 2014 Apr 15;6(1):8
pubmed: 24735657
Genome Res. 2012 Apr;22(4):623-32
pubmed: 22300631
Thorax. 2001 Nov;56(11):835-8
pubmed: 11641506
Adv Exp Med Biol. 2007;612:88-103
pubmed: 18161483
Pediatrics. 1998 Aug;102(2 Pt 3):507-11
pubmed: 9685454
Epigenetics Chromatin. 2015 Oct 19;8:43
pubmed: 26500701
Am J Med Genet B Neuropsychiatr Genet. 2015 Jan;168B(1):36-44
pubmed: 25355443
World J Pediatr. 2013 Aug;9(3):230-8
pubmed: 23335183
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
J Am Diet Assoc. 2002 Nov;102(11):1648-51
pubmed: 12449289
Clin Epigenetics. 2018 May 9;10:62
pubmed: 29760811
Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10522-7
pubmed: 22689993
Cancer Treat Rev. 2011;37 Suppl 1:S8-12
pubmed: 21601364
Clin Epigenetics. 2015 Mar 26;7:34
pubmed: 25874017
Nat Rev Genet. 2008 Jun;9(6):465-76
pubmed: 18463664
Biol Reprod. 1989 Feb;40(2):197-200
pubmed: 2497805
PLoS One. 2018 Jun 14;13(6):e0199091
pubmed: 29902267
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Am J Respir Crit Care Med. 2018 Jul 11;:
pubmed: 29995435
BMC Genomics. 2017 Jan 5;18(1):25
pubmed: 28056824
Genome Biol. 2014 Feb 04;15(2):R31
pubmed: 24495553
Am J Respir Crit Care Med. 2006 Aug 15;174(4):428-36
pubmed: 16709937
Hum Genet. 2007 Dec;122(5):505-14
pubmed: 17851693
J Epidemiol Community Health. 2014 Oct;68(10):934-41
pubmed: 24895184
BMJ. 1993 May 22;306(6889):1386-90
pubmed: 8518607