Prenatal and early life influences on epigenetic age in children

a study of mother-offspring pairs from two cohort studies

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

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Resumé

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.

OriginalsprogEngelsk
TidsskriftHuman Molecular Genetics
Vol/bind25
Udgave nummer1
Sider (fra-til)191-201
Antal sider11
ISSN0964-6906
DOI
StatusUdgivet - 1. jan. 2016

Fingeraftryk

Epigenomics
Cohort Studies
Mothers
DNA Methylation
Selenium
Longitudinal Studies
Parents
Smoking
Weights and Measures
Research

Citer dette

Simpkin, A. J., Hemani, G., Suderman, M., Gaunt, T. R., Lyttleton, O., Mcardle, W. L., ... Smith, G. D. (2016). Prenatal and early life influences on epigenetic age in children: a study of mother-offspring pairs from two cohort studies. Human Molecular Genetics, 25(1), 191-201. https://doi.org/10.1093/hmg/ddv456
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. / Prenatal and early life influences on epigenetic age in children : a study of mother-offspring pairs from two cohort studies. I: Human Molecular Genetics. 2016 ; Bind 25, Nr. 1. s. 191-201.
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title = "Prenatal and early life influences on epigenetic age in children: a study of mother-offspring pairs from two cohort studies",
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.",
author = "Simpkin, {Andrew J} and Gibran Hemani and Matthew Suderman and Gaunt, {Tom R} and Oliver Lyttleton and Mcardle, {Wendy L} and Ring, {Susan M} and Sharp, {Gemma C} and Kate Tilling and Steve Horvath and Sonja Kunze and Annette Peters and Melanie Waldenberger and Cavin Ward-Caviness and Nohr, {Ellen A} and S{\o}rensen, {Thorkild I A} and Relton, {Caroline L} and Smith, {George Davey}",
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Simpkin, AJ, Hemani, G, Suderman, M, Gaunt, TR, Lyttleton, O, Mcardle, WL, Ring, SM, Sharp, GC, Tilling, K, Horvath, S, Kunze, S, Peters, A, Waldenberger, M, Ward-Caviness, C, Nohr, EA, Sørensen, TIA, Relton, CL & Smith, GD 2016, 'Prenatal and early life influences on epigenetic age in children: a study of mother-offspring pairs from two cohort studies', Human Molecular Genetics, bind 25, nr. 1, s. 191-201. https://doi.org/10.1093/hmg/ddv456

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

I: Human Molecular Genetics, Bind 25, Nr. 1, 01.01.2016, s. 191-201.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Prenatal and early life influences on epigenetic age in children

T2 - a study of mother-offspring pairs from two cohort studies

AU - Simpkin, Andrew J

AU - Hemani, Gibran

AU - Suderman, Matthew

AU - Gaunt, Tom R

AU - Lyttleton, Oliver

AU - Mcardle, Wendy L

AU - Ring, Susan M

AU - Sharp, Gemma C

AU - Tilling, Kate

AU - Horvath, Steve

AU - Kunze, Sonja

AU - Peters, Annette

AU - Waldenberger, Melanie

AU - Ward-Caviness, Cavin

AU - Nohr, Ellen A

AU - Sørensen, Thorkild I A

AU - Relton, Caroline L

AU - Smith, George Davey

N1 - © The Author 2015. Published by Oxford University Press.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

U2 - 10.1093/hmg/ddv456

DO - 10.1093/hmg/ddv456

M3 - Journal article

VL - 25

SP - 191

EP - 201

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 1

ER -