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.
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, andrew.simpkin@bristol.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Simpkin
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine.
authors.forename: Gibran
authors.initials: G
authors.lastname: Hemani
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine.
authors.forename: Matthew
authors.initials: M
authors.lastname: Suderman
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine.
authors.forename: Tom R
authors.initials: TR
authors.lastname: Gaunt
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lyttleton
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Mcardle
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine.
authors.forename: Gemma C
authors.initials: GC
authors.lastname: Sharp
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine.
authors.forename: Kate
authors.initials: K
authors.lastname: Tilling
authors.affiliation: Human Genetics, David Geffen School of Medicine, Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kunze
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München.
authors.forename: Melanie
authors.initials: M
authors.lastname: Waldenberger
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Cavin
authors.initials: C
authors.lastname: Ward-Caviness
authors.affiliation: Research Unit for Gynaecology and Obstetrics, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Nohr
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, The Novo Nordisk Foundation Center for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark and.
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Relton
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine.
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
mesh_terms: D000375:Aging / Q000235:genetics*; D001724:Birth Weight; D002648:Child; D015331:Cohort Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D008137:Longitudinal Studies; D009035:Mothers