Associations between accelerated parental biologic age, autism spectrum disorder, social traits, and developmental and cognitive outcomes in their children
Ashley Y. Song
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Search for more papers by this authorKelly Bakulski
Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA
Search for more papers by this authorJason I. Feinberg
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Search for more papers by this authorCraig Newschaffer
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
College of Health and Human Development, Pennsylvania State University, State College, Pennsylvania, USA
Search for more papers by this authorLisa A. Croen
Division of Research, Kaiser Permanente, Oakland, California, USA
Search for more papers by this authorIrva Hertz-Picciotto
Department of Public Health Sciences and The MIND Institute, School of Medicine, University of California-Davis, Davis, California, USA
Search for more papers by this authorRebecca J. Schmidt
Department of Public Health Sciences and The MIND Institute, School of Medicine, University of California-Davis, Davis, California, USA
Search for more papers by this authorHomayoon Farzadegan
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Search for more papers by this authorKristen Lyall
A.J. Drexel Autism Institute, Drexel University, Philadelphia, Pennsylvania, USA
Search for more papers by this authorM. Daniele Fallin
Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
Search for more papers by this authorHeather E. Volk
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Search for more papers by this authorCorresponding Author
Christine Ladd-Acosta
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Correspondence
Christine Ladd-Acosta, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room W6509, Baltimore, MD 21205, USA.
Email: [email protected]
Search for more papers by this authorAshley Y. Song
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Search for more papers by this authorKelly Bakulski
Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA
Search for more papers by this authorJason I. Feinberg
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Search for more papers by this authorCraig Newschaffer
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
College of Health and Human Development, Pennsylvania State University, State College, Pennsylvania, USA
Search for more papers by this authorLisa A. Croen
Division of Research, Kaiser Permanente, Oakland, California, USA
Search for more papers by this authorIrva Hertz-Picciotto
Department of Public Health Sciences and The MIND Institute, School of Medicine, University of California-Davis, Davis, California, USA
Search for more papers by this authorRebecca J. Schmidt
Department of Public Health Sciences and The MIND Institute, School of Medicine, University of California-Davis, Davis, California, USA
Search for more papers by this authorHomayoon Farzadegan
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Search for more papers by this authorKristen Lyall
A.J. Drexel Autism Institute, Drexel University, Philadelphia, Pennsylvania, USA
Search for more papers by this authorM. Daniele Fallin
Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
Search for more papers by this authorHeather E. Volk
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Search for more papers by this authorCorresponding Author
Christine Ladd-Acosta
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Correspondence
Christine Ladd-Acosta, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room W6509, Baltimore, MD 21205, USA.
Email: [email protected]
Search for more papers by this authorHeather E. Volk and Christine Ladd-Acosta contributed equally
Funding information: Autism Speaks; National Institutes of Health (NIH) to Craig Newschaffer, M. Daniele Fallin, and Andrew Feinberg, Grant/Award Numbers: R01ES016443, R01ES017646; Johns Hopkins Genetic Resources Core Facility, Grant/Award Number: RRID:SCR_018669
Abstract
Parental age is a known risk factor for autism spectrum disorder (ASD), however, studies to identify the biologic changes underpinning this association are limited. In recent years, “epigenetic clock” algorithms have been developed to estimate biologic age and to evaluate how the epigenetic aging impacts health and disease. In this study, we examined the relationship between parental epigenetic aging and their child's prospective risk of ASD and autism related quantitative traits in the Early Autism Risk Longitudinal Investigation study. Estimates of epigenetic age were computed using three robust clock algorithms and DNA methylation measures from the Infinium HumanMethylation450k platform for maternal blood and paternal blood specimens collected during pregnancy. Epigenetic age acceleration was defined as the residual of regressing chronological age on epigenetic age while accounting for cell type proportions. Multinomial logistic regression and linear regression models were completed adjusting for potential confounders for both maternal epigenetic age acceleration (n = 163) and paternal epigenetic age acceleration (n = 80). We found accelerated epigenetic aging in mothers estimated by Hannum's clock was significantly associated with lower cognitive ability and function in offspring at 12 months, as measured by Mullen Scales of Early Learning scores (β = −1.66, 95% CI: −3.28, −0.04 for a one-unit increase). We also observed a marginal association between accelerated maternal epigenetic aging by Horvath's clock and increased odds of ASD in offspring at 36 months of age (aOR = 1.12, 95% CI: 0.99, 1.26). By contrast, fathers accelerated aging was marginally associated with decreased ASD risk in their offspring (aOR = 0.83, 95% CI: 0.68, 1.01). Our findings suggest epigenetic aging could play a role in parental age risks on child brain development.
CONFLICT OF INTEREST
The authors declare they have no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
Data are available through the National Institute of Mental Health Data Archive (NDA) under the collections for the EARLI network (1600). https://nda.nih.gov/edit_collection.html?id=1600.
Supporting Information
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Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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