Evidence map›Paper›PMID 25878217›Full record

ArticleInternational journal of epidemiology2015

Paternal sperm DNA methylation associated with early signs of autism risk in an autism-enriched cohort.

Jason I Feinberg, Kelly M Bakulski, Andrew E Jaffe, Rakel Tryggvadottir, Shannon C Brown, Lynn R Goldman, Lisa A Croen, Irva Hertz-Picciotto, Craig J Newschaffer, M Daniele Fallin and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of epidemiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 2 pooled it
8.2field-weighted citation impact, top 2% of its field
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

77 citing papers in PubMed, 2 syntheses or guidelines pooled it, 151 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

17 more citing papers are in PubMed but not listed here.

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

11 authors at 4 institutions in 1 country.

Jason I FeinbergJohns Hopkins Bloomberg School of Public Health, Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins University, Center for Epigenetics.
Kelly M BakulskiJohns Hopkins Bloomberg School of Public Health, Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins University, Center for Epigenetics, Johns Hopkins Bloomberg School of Public Health, Epidemiology.
Andrew E JaffeLieber Institute for Brain Development, Johns Hopkins Bloomberg School of Public Health, Mental Health and.
Rakel TryggvadottirJohns Hopkins University, Center for Epigenetics.
Shannon C BrownJohns Hopkins Bloomberg School of Public Health, Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Epidemiology.
Lynn R GoldmanGeorge Washington University, Milken Institute School of Public Health, Johns Hopkins Bloomberg School of Public Health.
Lisa A CroenKaiser Permanente, Division of Research, Autism Research Program.
Irva Hertz-PicciottoUniversity of California Davis School of Medicine, Public Health Sciences.
Craig J NewschafferDrexel University, A.J. Drexel Autism Institute, Drexel University School of Public Health, Epidemiology and Biostatistics.
M Daniele FallinJohns Hopkins Bloomberg School of Public Health, Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Mental Health and.
Andrew P FeinbergJohns Hopkins University, Center for Epigenetics, Johns Hopkins University School of Medicine, Medicine.
Johns Hopkins University · USDrexel University · USKaiser Permanente · USUniversity of California, Davis · US

Funding

Early Autism Risk Longitudinal Investigation (EARLI) NetworkR01ES016443 · NIEHS · DREXEL UNIVERSITY · PI NEWSCHAFFER, CRAIG J · 2008 to 2013
$15.6M
Environment, The Perinatal Epigenome, and Risk for Autism and Related DisordersR01ES017646 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI FALLIN, M DANIELE, FEINBERG, ANDREW P. · 2009 to 2013
$8.7M
NIEHS NIH HHS R01 ES017646NIEHS NIH HHS R01 ES16443
6 · The paper itself

Abstract

backgroundEpigenetic mechanisms such as altered DNA methylation have been suggested to play a role in autism, beginning with the classical association of Prader-Willi syndrome, an imprinting disorder, with autistic features.

objectivesHere we tested for the relationship of paternal sperm DNA methylation with autism risk in offspring, examining an enriched-risk cohort of fathers of autistic children.

methodsWe examined genome-wide DNA methylation (DNAm) in paternal semen biosamples obtained from an autism spectrum disorder (ASD) enriched-risk pregnancy cohort, the Early Autism Risk Longitudinal Investigation (EARLI) cohort, to estimate associations between sperm DNAm and prospective ASD development, using a 12-month ASD symptoms assessment, the Autism Observation Scale for Infants (AOSI). We analysed methylation data from 44 sperm samples run on the CHARM 3.0 array, which contains over 4 million probes (over 7 million CpG sites), including 30 samples also run on the Illumina Infinium HumanMethylation450 (450K) BeadChip platform (∼485 000 CpG sites). We also examined associated regions in an independent sample of post-mortem human brain ASD and control samples for which Illumina 450K DNA methylation data were available.

resultsUsing region-based statistical approaches, we identified 193 differentially methylated regions (DMRs) in paternal sperm with a family-wise empirical P-value [family-wise error rate (FWER)] <0.05 associated with performance on the Autism Observational Scale for Infants (AOSI) at 12 months of age in offspring. The DMRs clustered near genes involved in developmental processes, including many genes in the SNORD family, within the Prader-Willi syndrome gene cluster. These results were consistent among the 75 probes on the Illumina 450K array that cover AOSI-associated DMRs from CHARM. Further, 18 of 75 (24%) 450K array probes showed consistent differences in the cerebellums of autistic individuals compared with controls.

conclusionsThese data suggest that epigenetic differences in paternal sperm may contribute to autism risk in offspring, and provide evidence that directionally consistent, potentially related epigenetic mechanisms may be operating in the cerebellum of individuals with autism.

Indexed as

DNA MethylationAdultAutism Spectrum DisorderEpigenesis, GeneticFathersFemaleHumansInfantMaleMiddle AgedProspective StudiesPsychiatric Status Rating ScalesSpermatozoaautism riskDNA methylationEpigeneticssperm

Identifiers

PMID25878217
PMCPMC4598797
OpenAlexW2135660192

What OpenQuestion holds

Textmetadata
Read underepoch 390

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 OpenQuestion graph.