Prenatal adverse environment is associated with epigenetic age deceleration at birth and hypomethylation at the hypoxia-responsive EP300 gene.

Publisher: Biomed Central Country of Publication: Germany NLM ID: 101516977 Publication Model: Electronic Cited Medium: Internet ISSN: 1868-7083 (Electronic) Linking ISSN: 18687075 NLM ISO Abbreviation: Clin Epigenetics Subsets: MEDLINE

Publication: Oct./Nov. 2011- : London : Biomed Central
Original Publication: Berlin : Springer-Verlag

DNA Methylation*; Diseases in Twins/*diagnosis ; E1A-Associated p300 Protein/*genetics ; Placenta/*chemistry ; Schizophrenia/*diagnosis ; Twins, Monozygotic/*genetics; Diseases in Twins/cerebrospinal fluid ; Diseases in Twins/genetics ; Early Diagnosis ; Epigenesis, Genetic ; Female ; Humans ; Multifactorial Inheritance ; Pregnancy ; Pregnancy Trimester, Third/cerebrospinal fluid ; Pregnancy Trimester, Third/genetics ; Promoter Regions, Genetic ; Prospective Studies ; Schizophrenia/genetics ; Spain

Background: Obstetric complications have long been retrospectively associated with a wide range of short- and long-term health consequences, including neurodevelopmental alterations such as those observed in schizophrenia and other psychiatric disorders. However, prospective studies assessing fetal well-being during pregnancy tend to focus on perinatal complications as the final outcome of interest, while there is a scarcity of postnatal follow-up studies. In this study, the cerebroplacental ratio (CPR), a hemodynamic parameter reflecting fetal adaptation to hypoxic conditions, was analyzed in a sample of monozygotic monochorionic twins (60 subjects), part of them with prenatal complications, with regard to (i) epigenetic age acceleration, and (ii) DNA methylation at genes included in the polygenic risk score (PRS) for schizophrenia, and highly expressed in placental tissue.
Results: Decreased CPR measured during the third trimester was associated with epigenetic age deceleration (β = 0.21, t = 3.362, p = 0.002). Exploration of DNA methylation at placentally expressed genes of the PRS for schizophrenia revealed methylation at cg06793497 (EP300 gene) to be associated with CPR (β = 0.021, t = 4.385; p = 0.00008, FDR-adjusted p = 0.11). This association was reinforced by means of an intrapair analysis in monozygotic twins discordant for prenatal suffering (β = 0.027, t = 3.924, p = 0.001).
Conclusions: Prenatal adverse environment during the third trimester of pregnancy is associated with both (i) developmental immaturity in terms of epigenetic age, and (ii) decreased CpG-specific methylation in a gene involved in hypoxia response and schizophrenia genetic liability.

Curr Opin Psychiatry. 2017 May;30(3):191-196. (PMID: 28230630)
Am J Psychiatry. 2000 Sep;157(9):1511-3. (PMID: 10964873)
BMC Med Genet. 2018 Mar 5;19(1):36. (PMID: 29506490)
Neurotoxicol Teratol. 2018 Mar - Apr;66:80-93. (PMID: 29307795)
BMJ Open. 2016 Jun 15;6(6):e008916. (PMID: 27311899)
Brain Res. 2009 Feb 13;1254:1-9. (PMID: 19103185)
Eur Psychiatry. 2015 Sep;30(6):715-8. (PMID: 25952135)
Am J Psychiatry. 1992 Oct;149(10):1355-61. (PMID: 1530072)
Am J Psychiatry. 2002 Sep;159(9):1514-20. (PMID: 12202271)
Nat Med. 2018 Jun;24(6):792-801. (PMID: 29808008)
Am J Obstet Gynecol. 2015 Jul;213(1):5-15. (PMID: 26113227)
Epigenomics. 2010 Feb;2(1):139-50. (PMID: 22122750)
BMC Bioinformatics. 2012 May 08;13:86. (PMID: 22568884)
Am J Psychiatry. 2002 Jul;159(7):1080-92. (PMID: 12091183)
Nat Rev Dis Primers. 2015 Nov 19;1:15071. (PMID: 27189754)
Bioinformatics. 2014 May 15;30(10):1363-9. (PMID: 24478339)
Hum Mol Genet. 2011 Dec 15;20(24):4786-96. (PMID: 21908516)
Nat Commun. 2014 Nov 26;5:5592. (PMID: 25424739)
Clin Epigenetics. 2017 Jul 25;9:75. (PMID: 28770015)
J Matern Fetal Neonatal Med. 2014 Nov;27(16):1633-6. (PMID: 24298956)
PLoS One. 2013 Jun 27;8(6):e67489. (PMID: 23826308)
Clin Epigenetics. 2018 Oct 16;10(1):123. (PMID: 30326963)
Am J Obstet Gynecol. 1979 Nov 1;135(5):637-46. (PMID: 507116)
Arch Gen Psychiatry. 2002 Jan;59(1):35-41. (PMID: 11779280)
Mol Cell. 2013 Jan 24;49(2):359-367. (PMID: 23177740)
Nature. 2014 Jul 24;511(7510):421-7. (PMID: 25056061)
Semin Fetal Neonatal Med. 2010 Dec;15(6):342-8. (PMID: 20675206)
Semin Fetal Neonatal Med. 2010 Dec;15(6):349-56. (PMID: 20855238)
Mech Ageing Dev. 2018 Sep;174:18-29. (PMID: 29337038)
Schizophr Res. 1996 Jul 5;20(3):307-14. (PMID: 8827858)
Am J Obstet Gynecol. 1999 Mar;180(3 Pt 1):750-6. (PMID: 10076158)
Br Med J. 1973 Oct 6;4(5883):28-31. (PMID: 4755210)
Ultrasound Obstet Gynecol. 2014 Mar;43(3):303-10. (PMID: 24488879)
Br J Obstet Gynaecol. 1997 Oct;104(10):1203-7. (PMID: 9333002)
Schizophr Bull. 1994;20(3):423-32. (PMID: 7526445)
Am J Psychiatry. 2010 Feb;167(2):160-9. (PMID: 20048021)
PLoS One. 2014 Aug 29;9(8):e103639. (PMID: 25171170)
Clin Epigenetics. 2016 Sep 06;8:92. (PMID: 27602172)
Biol Psychiatry. 2010 Aug 15;68(4):314-9. (PMID: 20674602)
Aging (Albany NY). 2016 Sep 28;8(9):1844-1865. (PMID: 27690265)
J Obstet Gynaecol Res. 2018 May;44(5):831-839. (PMID: 29436080)
Child Dev. 2013 Jan-Feb;84(1):58-75. (PMID: 21883162)
Clin Epigenetics. 2017 Sep 15;9:100. (PMID: 28932320)
J Am Acad Child Adolesc Psychiatry. 2018 May;57(5):321-328.e2. (PMID: 29706161)
Mol Biol Evol. 2011 Feb;28(2):1075-81. (PMID: 21030426)
Acta Psychiatr Scand. 2018 Feb;137(2):88-97. (PMID: 29288491)
Genom Data. 2016 May 26;9:22-4. (PMID: 27330998)
Neurosci Biobehav Rev. 2014 Jun;43:137-62. (PMID: 24747487)
Clin Epigenetics. 2017 May 8;9:49. (PMID: 28503212)
Genome Biol. 2013;14(10):R115. (PMID: 24138928)
Biol Psychiatry. 2008 Nov 1;64(9):797-802. (PMID: 18486103)
Genome Biol. 2016 Oct 7;17(1):206. (PMID: 27717399)
Genome Biol. 2015 Dec 17;16:266. (PMID: 26673150)
Schizophr Bull. 1976;2(3):360-401. (PMID: 1034336)

Keywords: DNA methylation; EP300 gene; Epigenetic clock; Hypoxia; Monozygotic twins; Obstetric complications; Prenatal stress; Schizophrenia

EC 2.3.1.48 (E1A-Associated p300 Protein)
EC 2.3.1.48 (EP300 protein, human)

Date Created: 20190511 Date Completed: 20200318 Latest Revision: 20200318

20250114

PMC6507133

10.1186/s13148-019-0674-5

31072398