Elevated polygenic burden for autism is associated with differential DNA methylation at birth.

BioRxiv : the Preprint Server for Biology
Eilis HannonJonathan Mill


Background: Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder characterized by deficits in social communication and restricted, repetitive behaviors, interests, or activities. The etiology of ASD involves both inherited and environmental risk factors, with epigenetic processes hypothesized as one mechanism by which both genetic and non-genetic variation influence gene regulation and pathogenesis. Methods: We quantified neonatal methylomic variation in 1,263 infants - of whom ~50% went on to subsequently develop ASD - using DNA isolated from a unique collection of archived blood spots taken shortly after birth. We used matched genetic data from the same individuals to examine the molecular consequences of ASD genetic risk variants, identifying methylomic variation associated with elevated polygenic burden for ASD. In addition, we performed DNA methylation quantitative trait loci (mQTL) mapping to prioritize target genes from ASD GWAS findings. Results: Although we did not identify specific loci showing consistent changes in neonatal DNA methylation associated with later ASD, we found a significant association between increased polygenic burden for autism and methylomic variation at two CpG sites located prox...Continue Reading

Related Concepts

Genome-Wide Association Study
Pathogenic Aspects
Quantitative Trait Loci
DNA Methylation [PE]
DNA Methylation
Neurodevelopmental Disorders
Autistic Disorder

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