Journal
DEVELOPMENT AND PSYCHOPATHOLOGY
Volume 34, Issue 3, Pages 854-863Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0954579420001662
Keywords
ALSPAC; autistic traits; DNA methylation; longitudinal; methylome-wide
Categories
Funding
- UK Medical Research Council
- Wellcome Trust [102215/2/13/2]
- BBSRC [BBI025751/1, BB/I025263/1]
- MRC Integrative Epidemiology Unit at the University of Bristol [MC UU 12013/2, MC UU 12013/8]
- Erasmus MC
- Erasmus University Rotterdam
- Netherlands Organization for Health Research and Development
- Ministry of Health, Welfare and Sport
- Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]
- Genetic Laboratory of the Department of Internal Medicine, Erasmus MC
- National Institute of Child and Human Development [R01HD068437]
- Economic and Social Research Council [ES/R005516/1]
- Netherlands Organization for Scientific Research (NWO ZonMw VENI) [91618147]
- European Union [707404]
- University of Bristol
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The study explored prospective associations between DNA methylation and trajectories of social communication deficits from childhood to adolescence using ALSPAC data. Differential DNA methylation at three loci in the genome differentiated children following high versus low trajectories of social communication deficits specifically in the neonatal period. However, further replication studies are needed to confirm these potentially novel findings.
While previous studies suggest that both genetic and environmental factors play an important role in the development of autism-related traits, little is known about potential biological mechanisms underlying these associations. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we examined prospective associations between DNA methylation (DNAm: n(birth) = 804, n(age 7) = 877) and trajectories of social communication deficits at age 8-17 years. Methylomic variation at three loci across the genome (false discovery rate = 0.048) differentiated children following high (n = 80) versus low (n = 724) trajectories of social communication deficits. This differential DNAm was specific to the neonatal period and not observed at 7 years of age. Associations between DNAm and trajectory membership remained robust after controlling for co-occurring mental health problems (i.e., hyperactivity/inattention, conduct problems). The three loci identified at birth were not replicated in the Generation R Study. However, to the best of our knowledge, ALSPAC is the only study to date that is prospective enough to examine DNAm in relation to longitudinal trajectories of social communication deficits from childhood to adolescence. Although the present findings might point to potentially novel sites that differentiate between a high versus low trajectory of social communication deficits, the results should be considered tentative until further replicated.
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