Cited by 250Epigenetics and DNA MethylationBirth, Development, and HealthGenetic Syndromes and Imprinting

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Prenatal and early life influences on epigenetic age in children: a study of mother–offspring pairs from two cohort studies

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Simpkin, Andrew J., Hemani, Gibran, Suderman, Matthew, Gaunt, Tom R., Lyttleton, Oliver, Mcardle, Wendy L., Ring, Susan M., Sharp, Gemma C., Tilling, Kate, Horvath, Steve, Kunze, Sonja, Peters, Annette, Waldenberger, Melanie, Ward-Caviness, Cavin, Nohr, Ellen A., Sørensen, Thorkild I. A., Relton, Caroline L., Smith, George Davey·2016·Human Molecular Genetics

DOI 10.1093/hmg/ddv456PMC PMC4690495

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Abstract

DNA methylation-based biomarkers of aging are highly correlated with actual age. Departures of methylation-estimated age from actual age can be used to define epigenetic measures of child development or age acceleration (AA) in adults. Very little is known about genetic or environmental determinants of these epigenetic measures of aging. We obtained DNA methylation profiles using Infinium HumanMethylation450 BeadChips across five time-points in 1018 mother-child pairs from the Avon Longitudinal Study of Parents and Children. Using the Horvath age estimation method, we calculated epigenetic age for these samples. AA was defined as the residuals from regressing epigenetic age on actual age. AA was tested for associations with cross-sectional clinical variables in children. We identified associations between AA and sex, birth weight, birth by caesarean section and several maternal characteristics in pregnancy, namely smoking, weight, BMI, selenium and cholesterol level. Offspring of non-drinkers had higher AA on average but this difference appeared to resolve during childhood. The associations between sex, birth weight and AA found in ARIES were replicated in an independent cohort (GOYA). In children, epigenetic AA measures are associated with several clinically relevant variables, and early life exposures appear to be associated with changes in AA during adolescence. Further research into epigenetic aging, including the use of causal inference methods, is required to better our understanding of aging.

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Figure 1. Horvath (left) and Hannum (right) predicted ages against actual ages from a random sample of 1018 individuals from the ARIES study.CC BY · PubMed Central

Figure 2. Bland–Altman plot of Horvath predicted age minus Hannum predicted age.CC BY · PubMed Central

Figure 3. AA differences by sex over the life course.CC BY · PubMed Central

Figure 4. Birth weight category and AA in GOYA newborns (top left), ARIES newborns (top right), ARIES children (bottom left) and ARIES adolescents (bottom right).CC BY · PubMed Central

Figure 5. SNP heritability estimates for AA at each time point using unrelated individuals. There is a larger genetic component when individuals increase in age.CC BY · PubMed Central

Figure 6. Heritability analysis of AA. The analysis was performed for each mother–child time-point combination (this was done to improve power), showing a general increase in genetic variance for AA as individuals get older. AN, AnteNatal clinic; FOM, Follow-on Mother's clinic.CC BY · PubMed Central

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Authors: Simpkin, A. J., Hemani, G., Suderman, M., Gaunt, T. R., Lyttleton, O., Mcardle, W. L., Ring, S. M., Sharp, G. C., Tilling, K., Horvath, S., Kunze, S., Peters, A., Waldenberger, M., Ward-Caviness, C., Nohr, E. A., Sørensen, T. I. A., Relton, C. L., & Smith, G. D.
Affiliations: MRC Integrative Epidemiology Unit (GB)
University of Bristol (GB)
University of California, Los Angeles (US)
Helmholtz Munich (DE)
University of Southern Denmark (DK)
University of Copenhagen (DK)
Corresponding author: Simpkin, Andrew J.
ORCID: Simpkin, Andrew J.
Hemani, Gibran
Suderman, Matthew
Gaunt, Tom R.
Mcardle, Wendy L.
Ring, Susan M.
Sharp, Gemma C.
Tilling, Kate
Horvath, Steve
Kunze, Sonja
Peters, Annette
Ward-Caviness, Cavin
Nohr, Ellen A.
Sørensen, Thorkild I. A.
Relton, Caroline L.
Smith, George Davey
Venue: Human Molecular Genetics
Publisher: Oxford University Press (OUP)
Published: 2015-11-05
Volume: 25
Issue: 1
Pages: 191-201
ISSN: 0964-6906 (ISSN-L)
1460-2083
DOI: 10.1093/hmg/ddv456
PMC: PMC4690495
OpenAlex: W2158554646
Cited by: 246
References: 31
Citations by year: 2026: 14 · 2025: 7 · 2024: 24 · 2023: 22 · 2022: 18 · 2021: 30 · 2020: 57 · 2019: 19 · 2018: 22 · 2017: 21 · 2016: 11 · 2015: 1
FWCI: 7.96
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
Locations: Human Molecular Genetics (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, cc-by)
PubMed (publishedVersion)
Bristol Research (University of Bristol) (publishedVersion, cc-by)
eScholarship (California Digital Library) (submittedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by)
Site cant be reached (submittedVersion, cc-by)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Explore Bristol Research (submittedVersion, cc-by)
Newcastle University ePrints (Newcastle Univesity) (cc-by)
Funders: UK Economic & Social Research Council (RES-060-23-0011)
UK Medical Research Council (G0601625, G0600705 and MR/L011824/1)
European Research Council (269874)
the BBSRC (BBI025751/1 and BB/I025263/1)
the Medical Research Council (MRC) and the Wellcome Trust (102215/2/13/1)
NIH
the auspices of the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_12013/2, MC_UU_12013/8, MRC_UU_12013/9)
German Federal Ministry of Education and Research (01ZX1313A-2014)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
Keywords: epigenetic age, accelerated aging, DNA methylation, prenatal exposure, early life exposure, mother-child pairs, birth weight, cesarean section, maternal smoking, maternal cholesterol, sex differences, adolescence, child development, Avon Longitudinal Study of Parents and Children
MeSH terms: Aging, Birth Weight, Child, Humans, Longitudinal Studies, Mothers, Cohort Studies, DNA Methylation, Epigenesis, Genetic

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Prenatal and early life influences on epigenetic age in children: a study of mother–offspring pairs from two cohort studies

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