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

AbstractPrevious 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 meth ylome-wide association study (MWAS). We did not identify significant CpGs associated with SCDC. The most significant CpG site was cg14379490, on chromosome 9 (MWAS beta = − 1.78 ± 0.35,p value  = 5.34 × 10−7). Using methylation data for autism in peripheral tissues, we did not identify a significant concordance in effect direction of CpGs withp value<  10−4 in the SCDC MWAS (binomial sign test,p value>  0.5). In contrast, using methylation data for autism from post-mortem brain tissues, we identify a significant concordance in effect direction of CpGs with ap value<  10−4 in the SCDC MWAS (binomial sign test,p value  = 0.004). Supporting this, we observe an enrichment for genes that are dysregulated in the post-mortem autism brain (one-sided Wilcoxon rank-sum test,p value  = 6.22 × 10−5). Finally, integrating genome-wide association study (GWAS) data for autism (n = 46,350) with mQTL maps from cord-blood (n = 771), we demonstrate ...
Source: Molecular Autism - Category: Molecular Biology Source Type: research