Epigenetic signature of preterm birth in adult twins

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Abstract

Background: Preterm birth is a leading cause of perinatal mortality and long-term health consequences. Epigenetic mechanisms may have been at play in preterm birth survivors, and these could be persistent and detrimental to health later in life.

Methods: We performed a genome-wide DNA methylation profiling in adult twins of premature birth to identify genomic regions under differential epigenetic regulation in 144 twins with a median age of 33 years (age range 30-36).

Results: Association analysis detected three genomic regions annotated to the SDHAP3, TAGLN3 and GSTT1 genes on chromosomes 5, 3 and 22 (FWER: 0.01, 0.02 and 0.04) respectively. These genes display strong involvement in neurodevelopmental disorders, cancer susceptibility and premature delivery. The three identified significant regions were successfully replicated in an independent sample of twins of even older age (median age 66, range 56-80) with similar regulatory patterns and nominal p values < 5.05e-04. Biological pathway analysis detected five significantly enriched pathways all explicitly involved in immune responses.

Conclusion: We have found novel evidence associating premature delivery with epigenetic modification of important genes/pathways and revealed that preterm birth, as an early life event, could be related to differential methylation regulation patterns observable in adults and even at high ages which could potentially mediate susceptibility to age-related diseases and adult health.

Original languageEnglish
Article number87
JournalClinical Epigenetics
Volume10
Number of pages10
ISSN1868-7075
DOIs
Publication statusPublished - 2018

Fingerprint

Premature Birth
Epigenomics
Health
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 3
Perinatal Mortality
DNA Methylation
Survivors
Neoplasms

Keywords

  • Adults
  • Epigenetics
  • Epigenome-wide association study
  • Preterm birth
  • Twins

Cite this

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title = "Epigenetic signature of preterm birth in adult twins",
abstract = "Background: Preterm birth is a leading cause of perinatal mortality and long-term health consequences. Epigenetic mechanisms may have been at play in preterm birth survivors, and these could be persistent and detrimental to health later in life.Methods: We performed a genome-wide DNA methylation profiling in adult twins of premature birth to identify genomic regions under differential epigenetic regulation in 144 twins with a median age of 33 years (age range 30-36).Results: Association analysis detected three genomic regions annotated to the SDHAP3, TAGLN3 and GSTT1 genes on chromosomes 5, 3 and 22 (FWER: 0.01, 0.02 and 0.04) respectively. These genes display strong involvement in neurodevelopmental disorders, cancer susceptibility and premature delivery. The three identified significant regions were successfully replicated in an independent sample of twins of even older age (median age 66, range 56-80) with similar regulatory patterns and nominal p values < 5.05e-04. Biological pathway analysis detected five significantly enriched pathways all explicitly involved in immune responses. Conclusion: We have found novel evidence associating premature delivery with epigenetic modification of important genes/pathways and revealed that preterm birth, as an early life event, could be related to differential methylation regulation patterns observable in adults and even at high ages which could potentially mediate susceptibility to age-related diseases and adult health.",
keywords = "Adults, Epigenetics, Epigenome-wide association study, Preterm birth, Twins",
author = "Qihua Tan and Shuxia Li and Morten Frost and Marianne Nygaard and Mette Soerensen and Martin Larsen and Kaare Christensen and Lene Christiansen",
year = "2018",
doi = "10.1186/s13148-018-0518-8",
language = "English",
volume = "10",
journal = "Clinical Epigenetics (Print)",
issn = "1868-7075",
publisher = "BioMed Central",

}

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T1 - Epigenetic signature of preterm birth in adult twins

AU - Tan, Qihua

AU - Li, Shuxia

AU - Frost, Morten

AU - Nygaard, Marianne

AU - Soerensen, Mette

AU - Larsen, Martin

AU - Christensen, Kaare

AU - Christiansen, Lene

PY - 2018

Y1 - 2018

N2 - Background: Preterm birth is a leading cause of perinatal mortality and long-term health consequences. Epigenetic mechanisms may have been at play in preterm birth survivors, and these could be persistent and detrimental to health later in life.Methods: We performed a genome-wide DNA methylation profiling in adult twins of premature birth to identify genomic regions under differential epigenetic regulation in 144 twins with a median age of 33 years (age range 30-36).Results: Association analysis detected three genomic regions annotated to the SDHAP3, TAGLN3 and GSTT1 genes on chromosomes 5, 3 and 22 (FWER: 0.01, 0.02 and 0.04) respectively. These genes display strong involvement in neurodevelopmental disorders, cancer susceptibility and premature delivery. The three identified significant regions were successfully replicated in an independent sample of twins of even older age (median age 66, range 56-80) with similar regulatory patterns and nominal p values < 5.05e-04. Biological pathway analysis detected five significantly enriched pathways all explicitly involved in immune responses. Conclusion: We have found novel evidence associating premature delivery with epigenetic modification of important genes/pathways and revealed that preterm birth, as an early life event, could be related to differential methylation regulation patterns observable in adults and even at high ages which could potentially mediate susceptibility to age-related diseases and adult health.

AB - Background: Preterm birth is a leading cause of perinatal mortality and long-term health consequences. Epigenetic mechanisms may have been at play in preterm birth survivors, and these could be persistent and detrimental to health later in life.Methods: We performed a genome-wide DNA methylation profiling in adult twins of premature birth to identify genomic regions under differential epigenetic regulation in 144 twins with a median age of 33 years (age range 30-36).Results: Association analysis detected three genomic regions annotated to the SDHAP3, TAGLN3 and GSTT1 genes on chromosomes 5, 3 and 22 (FWER: 0.01, 0.02 and 0.04) respectively. These genes display strong involvement in neurodevelopmental disorders, cancer susceptibility and premature delivery. The three identified significant regions were successfully replicated in an independent sample of twins of even older age (median age 66, range 56-80) with similar regulatory patterns and nominal p values < 5.05e-04. Biological pathway analysis detected five significantly enriched pathways all explicitly involved in immune responses. Conclusion: We have found novel evidence associating premature delivery with epigenetic modification of important genes/pathways and revealed that preterm birth, as an early life event, could be related to differential methylation regulation patterns observable in adults and even at high ages which could potentially mediate susceptibility to age-related diseases and adult health.

KW - Adults

KW - Epigenetics

KW - Epigenome-wide association study

KW - Preterm birth

KW - Twins

U2 - 10.1186/s13148-018-0518-8

DO - 10.1186/s13148-018-0518-8

M3 - Journal article

VL - 10

JO - Clinical Epigenetics (Print)

JF - Clinical Epigenetics (Print)

SN - 1868-7075

M1 - 87

ER -