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Integrated genetic and methylomic analyses identify shared biology between autism and autistic traits

Authors: Massrali, Aicha; Brunel, Helena; Hannon, Eilis; Wong, Chloe; iPSYCH-MINERvA Epigenetics Group; Baron-Cohen, Simon; Warrier, Varun;

Integrated genetic and methylomic analyses identify shared biology between autism and autistic traits

Abstract

Abstract Previous studies have identified differences in DNA methylation in autistic individuals compared to neurotypical individuals. Yet, it is unclear if this extends to autistic traits – subclinical manifestation of autism features in the general population. Here, we investigate the association between DNA methylation at birth (cord blood), and scores on the Social and Communication Disorders Checklist (SCDC), a measure of autistic traits, in 701 8-year olds, by conducting a methylome-wide association study (MWAS) using DNA methylation data from cord-blood. Whilst did not identify significant loci demonstrating differential methylation, we observe a degree of overlap between the SCDC MWAS and post-mortem brain methylation signature in autism. Validating this, we observe an enrichment for genes that are dysregulated in the post-mortem autism brain. Finally, integrating genome-wide data from more than 40,000 individuals and mQTL maps from cord-blood, we demonstrate that mQTLs of CpGs associated with SCDC scores at different P-value thresholds are significantly shifted towards lower P-values in a GWAS for autism. We validate this using a GWAS of SCDC, and demonstrate a lack of enrichment in a GWAS of Alzheimer’s disease. Our results highlight the shared cross-tissue epigenetic architecture of autism and autistic traits, and demonstrate that mQTLs associated with methylation changes in childhood autistic traits are enriched for common genetic variants associated with autism and autistic traits.

Country
United Kingdom
Keywords

Transcription, Genetic, Research, Quantitative Trait Loci, Brain, DNA Methylation, Polymorphism, Single Nucleotide, Gene Expression Regulation, Postmortem Changes, Humans, CpG Islands, Neurology. Diseases of the nervous system, Autistic Disorder, RC346-429, Child, Social Communication Disorder, Genome-Wide Association Study

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
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