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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). 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 with  p  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 a  p  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 that mQTLs of CpGs associated with SCDC scores at  p  value thresholds of 0.01 and 0.005 are significantly shifted toward lower  p  values in the GWAS for autism ( p  < 5 × 10 −3 ). We provide additional support for 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 methylation architecture of autism and autistic traits, and demonstrate that mQTLs associated with differences in DNA methylation associated with childhood autistic traits are enriched for common genetic variants associated with autism and autistic traits.   Electronic supplementary material  The online version of this article (10.1186/s13229-019-0279-z) contains supplementary material, which is available to authorized users.

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