Evidence map›Paper›PMID 40819066›Full record

ArticleJournal of neurodevelopmental disorders2025

An epigenome-wide association study in the case-control study to explore early development identifies differential DNA methylation near ZFP57 as associated with autistic traits.

Ellen M Howerton, Valerie Morrill, Rose Schrott, Jason Daniels, Ashley Y Song, Kelly Benke, Heather Volk, Homayoon Farzadegan, Aimee Anido Alexander, Amanda L Tapia and 6 more

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In one paragraph

Article in Journal of neurodevelopmental disorders, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Ellen M HowertonDepartment of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Valerie MorrillDepartment of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Rose SchrottDepartment of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Jason DanielsDepartment of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Ashley Y SongDepartment of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Kelly BenkeDepartment of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Heather VolkDepartment of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Homayoon FarzadeganDepartment of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Aimee Anido AlexanderNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Amanda L TapiaDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Gabriel S DichterDepartment of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Lisa A CroenDivision of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Lisa WigginsNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Genevieve WojcikDepartment of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
M Daniele FallinOffice of the Dean, Emory University Rollins School of Public Health, Atlanta, GA, USA.
Christine Ladd-AcostaDepartment of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA. claddac1@jhu.edu.

Funding

Expanding the Value of the EARLI study: Small Cohort with Big DataR24ES030893 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI VOLK, HEATHER E · 2020 to 2024
$2.0M
CDC HHS U01DD001293CDC HHS U01DD001297CDC HHS U10DD000181NIH HHS R24ES030893
6 · The paper itself

Abstract

backgroundQuantitative measures of autism spectrum disorder (ASD)-related traits can provide insight into trait presentation across the population. Previous studies have identified epigenomic variation associated with ASD diagnosis, but few have evaluated quantitative traits. We sought to identify DNA methylation patterns in child blood associated with Social Responsiveness Scale score, Second Edition (SRS).

methodsWe conducted an epigenome-wide association study of SRS in child blood at approximately age 5 in the Study to Explore Early Development, a case-control study of ASD in the United States. We measured DNA methylation using the Illumina 450K array with 857 samples in our analysis after quality control. We performed regression of the M-value to identify single sites or differentially methylated regions (DMRs) associated with SRS scores, adjusting for sources of biological and technical variation. We examined methylation quantitative trait loci and conducted gene-ontology-term pathway analyses for regions of interest.

resultsWe identified a region about 3.5 kb upstream of ZFP57 on chromosome 6 as differentially methylated (family-wise error rate [fwer] < 0.1) by continuous SRS T-score in the full sample (N = 857; fwer = 0.074) and among ASD cases only (N = 390; fwer = 0.021). ZFP57 encodes a transcription factor involved in imprinting regulation and maintenance, and this DMR has been previously associated with ASD in brain and buccal samples.

conclusionsBlood DNA methylation near ZFP57 was associated (fwer < 0.1) with SRS in the full population sample and appears to be largely driven by trait heterogeneity within the autism case group. Our results indicate DNA methylation associations with ASD quantitative traits are observable in a population and provide insights into specific biologic changes related to autism trait heterogeneity.

Indexed as

Autism Spectrum DisorderDNA-Binding ProteinsDNA MethylationEpigenomeTranscription FactorsCase-Control StudiesChild, PreschoolFemaleGenome-Wide Association StudyHumansMaleQuantitative Trait LociRepressor ProteinsDNA-Binding ProteinsRepressor ProteinsTranscription FactorsZFP57 protein, humanAutismDNA methylationQuantitative traitSocial Responsiveness Scale

Identifiers

PMID40819066
PMCPMC12357374

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.