Sandro Marini1, Kathryn A Davis1, Thomas W Soare2, Yiwen Zhu1, Matthew J Suderman3, Andrew J Simpkin4, Andrew D A C Smith5, Erika J Wolf6, Caroline L Relton7, Erin C Dunn8. 1. Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA. 2. Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, 02115, USA. 3. MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, BSB 1TH, UK. 4. MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, BSB 1TH, UK; School of Mathematics, Statistics and Applied Mathematics, National University of Ireland, Galway, H91TK33, Ireland. 5. Applied Statistics Group, University of the West of England, Bristol, BS16 1QY, UK. 6. National Center for PTSD at VA Boston Healthcare System, Boston, MA, 02130, USA; Boston University School of Medicine, Department of Psychiatry, Boston, MA, 02118, USA. 7. MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, BSB 1TH, UK; Institute of Genetic Medicine, University of Newcastle, Newcastle upon Tyne, NE1 3BZ, UK. 8. Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, 02115, USA; McCance Center for Brain Health at Massachusetts General Hospital, Boston, MA, 02114, USA. Electronic address: edunn2@mgh.harvard.edu.
Abstract
OBJECTIVES: Exposure to adversity has been linked to accelerated biological aging, which in turn has been shown to predict numerous physical and mental health problems. In recent years, measures of DNA methylation-based epigenetic age--known as "epigenetic clocks"--have been used to estimate accelerated epigenetic aging. Although a small number of studies have found an effect of adversity exposure on epigenetic age in children, none have investigated if there are "sensitive periods" when adversity is most impactful. METHODS: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 973), we tested the prospective association between repeated measures of childhood exposure to seven types of adversity on epigenetic age assessed at age 7.5 using the Horvath and Hannum epigenetic clocks. With a Least Angle Regression variable selection procedure, we evaluated potential sensitive period effects. RESULTS: We found that exposure to abuse, financial hardship, or neighborhood disadvantage during sensitive periods in early and middle childhood best explained variability in the deviation of Hannum-based epigenetic age from chronological age, even after considering the role of adversity accumulation and recency. Secondary sex-stratified analyses identified particularly strong sensitive period effects. These effects were undetected in analyses comparing children "exposed" versus "unexposed" to adversity. We did not identify any associations between adversity and epigenetic age using the Horvath epigenetic clock. CONCLUSIONS: Our results suggest that adversity may alter methylation processes in ways that either directly or indirectly perturb normal cellular aging and that these effects may be heightened during specific life stages.
OBJECTIVES: Exposure to adversity has been linked to accelerated biological aging, which in turn has been shown to predict numerous physical and mental health problems. In recent years, measures of DNA methylation-based epigenetic age--known as "epigenetic clocks"--have been used to estimate accelerated epigenetic aging. Although a small number of studies have found an effect of adversity exposure on epigenetic age in children, none have investigated if there are "sensitive periods" when adversity is most impactful. METHODS: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 973), we tested the prospective association between repeated measures of childhood exposure to seven types of adversity on epigenetic age assessed at age 7.5 using the Horvath and Hannum epigenetic clocks. With a Least Angle Regression variable selection procedure, we evaluated potential sensitive period effects. RESULTS: We found that exposure to abuse, financial hardship, or neighborhood disadvantage during sensitive periods in early and middle childhood best explained variability in the deviation of Hannum-based epigenetic age from chronological age, even after considering the role of adversity accumulation and recency. Secondary sex-stratified analyses identified particularly strong sensitive period effects. These effects were undetected in analyses comparing children "exposed" versus "unexposed" to adversity. We did not identify any associations between adversity and epigenetic age using the Horvath epigenetic clock. CONCLUSIONS: Our results suggest that adversity may alter methylation processes in ways that either directly or indirectly perturb normal cellular aging and that these effects may be heightened during specific life stages.
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