Journal article
SNP-associated differential methylation in ARHGEF38 : insights into genetic-epigenetic interactions
Epigenomics, Vol.17(9), pp.579-588
05/30/2025
DOI: 10.1080/17501911.2025.2513215
PMCID: PMC12143701
PMID: 40444651
Abstract
Objective
Associations have been seen between suicide and differential DNA methylation, with one study showing significant hypomethylation of ARHGEF38 in individuals with bipolar disorder who died by suicide. Our objective was to explore ARHGEF38 methylation in individuals with bipolar disorder and a history of suicide attempt.
Method
With pyrosequencing, we looked at the previously identified region of interest in ARHGEF38. We investigated the methylation levels of three CpG sites in 47 individuals with bipolar disorder and a history of suicide attempt, 47 individuals with bipolar disorder without a history of suicide attempt, and 47 non-bipolar disorder controls.
Results
None of the CpG sites measured had an association between groups, although there were distinct clusters of differential methylation in each group. Applying genotypes of SNPs found in the region of interest, rs2121558 and rs1447093, these clusters showed stepwise methylation at each CpG site, regardless of phenotype.
Conclusions
In this small sample size study, differential methylation in ARHGEF38 was not associated with history of suicide attempt, failing to replicate findings from a related outcome, suicide death. However, we did provide evidence of SNP and DNA methylation interplay in this region. This highlights the relevance of considering genetics when interrogating epigenetic mechanisms.
Details
- Title: Subtitle
- SNP-associated differential methylation in ARHGEF38 : insights into genetic-epigenetic interactions
- Creators
- Emese H C Kovács - University of IowaLucas G Casten - University of Iowa, PsychiatryNiamh Mullins - Icahn School of Medicine at Mount SinaiJenny G Richards - University of Iowa, RadiologyAislinn J Williams - University of Iowa, Iowa Neuroscience InstituteJohn A Wemmie - University of Iowa, Iowa Neuroscience InstituteVincent A Magnotta - University of Iowa, Iowa Neuroscience InstituteJess G Fiedorowicz - University of Iowa, PsychiatryJacob J Michaelson - University of Iowa, Iowa Neuroscience InstituteMarie E Gaine - University of Iowa, Iowa Neuroscience Institute
- Resource Type
- Journal article
- Publication Details
- Epigenomics, Vol.17(9), pp.579-588
- DOI
- 10.1080/17501911.2025.2513215
- PMID
- 40444651
- PMCID
- PMC12143701
- NLM abbreviation
- Epigenomics
- ISSN
- 1750-192X
- eISSN
- 1750-192X
- Publisher
- TAYLOR & FRANCIS LTD; ABINGDON
- Grant note
- Environmental Health Sciences Research Center (EHSRC) Career Advancement awarded to Marie E. Gaine, the National Institutes of Health (NIH): Q48
We thank the study participants for their willingness to participate in the study and Hsiang Wen of the Department of Psychiatry at the University of Iowa for sample collection and management. We also acknowledge the Iowa NeuroBank Core at the Carver College of Medicine (University of Iowa) for access to the PyroMark Q48.
- Language
- English
- Date published
- 05/30/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Communication Sciences and Disorders; Molecular Physiology and Biophysics; Psychiatry; Epidemiology; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Neurosurgery
- Record Identifier
- 9984824178602771
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