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Leveraging epigenetics to examine differences in developmental trajectories of social attention: A proof-of-principle study of DNA methylation in infants with older siblings with autism

Gui, Anna ; Jones, Emily J.H. ; Wong, Chloe C.Y. ; Meaburn, Emma ; Xia, Baocong ; Pasco, Greg ; Lloyd-Fox, Sarah ; Charman, Tony ; Bolton, Patrick ; Johnson, Mark H.

Infant behavior & development, 2020-08, Vol.60, p.101409, Article 101409 [同儕審閱期刊]

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題名:
Leveraging epigenetics to examine differences in developmental trajectories of social attention: A proof-of-principle study of DNA methylation in infants with older siblings with autism
著者: Gui, Anna ; Jones, Emily J.H. ; Wong, Chloe C.Y. ; Meaburn, Emma ; Xia, Baocong ; Pasco, Greg ; Lloyd-Fox, Sarah ; Charman, Tony ; Bolton, Patrick ; Johnson, Mark H.
主題: Analysis ; Autism ; Development and progression ; Developmental trajectory ; DNA ; DNA methylation ; Epigenetic inheritance ; Genetic polymorphisms ; Genetic research ; Infant siblings ; Infants ; Methylation ; Social attention
所屬期刊: Infant behavior & development, 2020-08, Vol.60, p.101409, Article 101409
描述: •Studying mechanisms underpinning ASD might benefit from incorporating epigenetic analysis into infant-sibling designs.•DNA methylation levels associated with early social attention are linked to genes involved in brain development and ASD.•Significant changes in the association between DNA methylation and behaviour were observed between 8 and 15 months.•Examining DNA methylation in age-homogeneous samples might allow to detect meaningful signals in relatively small samples. Preliminary evidence suggests that changes in DNA methylation, a widely studied epigenetic mechanism, contribute to the etiology of Autism Spectrum Disorder (ASD). However, data is primarily derived from post-mortem brain samples or peripheral tissue from adults. Deep-phenotyped longitudinal infant cohorts are essential to understand how epigenetic modifications relate to early developmental trajectories and emergence of ASD symptoms. We present a proof-of-principle study designed to evaluate the potential of prospective epigenetic studies of infant siblings of children with ASD. Illumina genome-wide 450 K DNA methylation data from buccal swabs was generated for 63 male infants at multiple time-points from 8 months to 2 years of age (total N = 107 samples). 11 of those infants received a diagnosis of ASD at 3 years. We conducted a series of analyses to characterize DNA methylation signatures associated with categorical outcome and neurocognitive measures from parent-report questionnaire, eye-tracking and electro-encephalography. Effects observed across the entire genome (epigenome-wide association analyses) suggest that collecting DNA methylation samples within infant-sibling designs allows for the detection of meaningful signals with smaller sample sizes than previously estimated. Mapping networks of co-methylated probes associated with neural correlates of social attention implicated enrichment of pathways involved in brain development. Longitudinal modelling found covariation between phenotypic traits and DNA methylation levels in the proximity of genes previously associated with cognitive development, although larger samples and more complete datasets are needed to obtain generalizable results. In conclusion, assessment of DNA methylation profiles at multiple time-points in infant-sibling designs is a promising avenue to comprehend developmental origins and mechanisms of ASD.
出版者: Elsevier Inc
語言: 英文
識別號: ISSN: 0163-6383
EISSN: 1879-0453
DOI: 10.1016/j.infbeh.2019.101409
資源來源: Elsevier ScienceDirect Journals Complete

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Leveraging epigenetics to examine differences in developmental trajectories of social attention: A proof-of-principle study of DNA methylation in infants with older siblings with autism

Gui, Anna ; Jones, Emily J.H. ; Wong, Chloe C.Y. ; Meaburn, Emma ; Xia, Baocong ; Pasco, Greg ; Lloyd-Fox, Sarah ; Charman, Tony ; Bolton, Patrick ; Johnson, Mark H.

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