An epigenetic biomarker for adult high-functioning autism spectrum disorder

Abstract

Increasing evidence suggests that epigenetic mechanisms play a role in the etiology of autism spectrum disorder (ASD). To date, several studies have attempted to identify epigenetic biomarkers for ASD. However, reliable markers remain to be established and most of these studies have focused on pediatric patients with ASD. In this study, we sought to find an epigenetic DNA methylation biomarker from peripheral blood for adult patients with high-functioning ASD. DNA methylation profiles were analyzed using the Illumina 450 K methylation array. To identify robust candidate markers, we employed two types of machine-learning algorithms for marker selection. We identified a potential marker (cg20793532) for which is the AUC value was 0.79. Notably, cg20793532 was annotated to the PPP2R2C gene, which was hypermethylated and down-regulated in blood from ASD patients compared to that in the controls. Although requiring careful interpretation, this pilot study seems to provide a potential blood biomarker for identifying individuals with high-functioning ASD.

Epigenetic clock analysis and increased plasminogen activator inhibitor-1 in high-functioning autism spectrum disorder

“…The participants are from our previously published study [ 32 ]. Briefly, we used two independent cohorts consisting of adult patients with high-functioning ASD and controls; the 1st cohort comprised 38 ASD cases and 31 controls, and the 2nd cohort was six ASD cases and 10 controls.…”

“…Genome-wide DNAm profiles of blood samples were measured using the Illumina Infinium 450 K platform as described elsewhere [ 32 ]. The Beta Mixture Quantile Dilation (BMIQ) method was used for array normalization [ 35 ].…”

“…Previous studies have reported altered DNAm profiles in the blood of individuals with ASD [ 31 , 32 ]. Furthermore, Pediatric-Buccal-Epigenetic clock acceleration was found in buccal epithelium cells of children with ASD compared to typically developing children [ 13 ].…”

The Promise of DNA Methylation in Understanding Multigenerational Factors in Autism Spectrum Disorders

“…Additionally, the field is working to identify potential mechanisms for transmission of risk through multiple generations. One of the most promising potential mechanisms is DNA methylation, an epigenetic mark that is hypothesized to be a mechanistic link between genetic and environmental risk ( Law and Holland 2019 ), as well as a potential biomarker for ASD ( Kimura et al, 2019 ; Zhu et al, 2019 ; Mordaunt et al, 2020 ; García-Ortiz et al, 2021 ; Garrido et al, 2021 ). Relatively few studies have examined DNA methylation in conjunction with grandparental or great-grandparental factors, despite the promising findings of existing multigenerational studies.…”

Simultaneous evaluation of antioxidative serum profiles facilitates the diagnostic screening of autism spectrum disorder in under-6-year-old children

“…Biomarkers that help screen children at risk during the pre-symptomatic period are useful for early diagnosis, patient stratification, and prediction of treatment response 18 . However, there are no blood-based diagnostic tools, nor is there sufficient evidence regarding the efficacy of specific pharmacological treatments for the core symptoms of ASD 4,[20][21][22] . As the Research Domain Criteria developed by the National Institute of Mental Health divides human mental functioning into five specific domains including specific behavioural or emotional components 23 , we may use biomarkers effectively in an integrated way and utilize them in our clinical activities in the future.…”