Journal article
Investigating the Relationship Between DNA Methylation, Genetic Variation, and Suicide Attempt in Bipolar Disorder
Archives of suicide research, Vol.30(1), pp.203-223
01/02/2026
DOI: 10.1080/13811118.2025.2511264
PMCID: PMC12309415
PMID: 40476679
Abstract
Objective
Individuals with bipolar disorder are at increased risk for suicide, and this can be influenced by a range of biological, clinical, and environmental risk factors. Biological components associated with suicide include DNA modifications that lead to changes in gene expression. Common genetic variation and DNA methylation changes are some of the most frequent types of DNA findings associated with an increased risk of suicide attempt. Importantly, the interplay between genetic predisposition and DNA methylation patterns is becoming more prevalent in genetic studies. We hypothesized that DNA methylation patterns in specific loci already genetically associated with suicide would be altered in individuals with bipolar disorder and a history of suicide attempt.
Method
To test this hypothesis, we searched the literature to identify common genetic variants (N = 34) previously associated with suicidal thoughts and behaviors in individuals with bipolar disorder. We then created a customized sequencing panel that covered our chosen genomic loci. We profiled DNA methylation patterns from blood samples collected from bipolar disorder participants with a history of suicide attempt (N = 55) and without (N = 51).
Results
We identified seven differentially methylated CpG sites and five differentially methylated regions between the two groups. Additionally, we found that DNA methylation changes in MIF and CACNA1C were associated with lethality or number of suicide attempts. Finally, we identified three meQTLs in SIRT1, IMPA2, and INPP1.
Conclusions
This study illustrates that DNA methylation is altered in individuals with bipolar disorder and a history of suicide attempts in regions known to harbor suicide-related variants.
Details
- Title: Subtitle
- Investigating the Relationship Between DNA Methylation, Genetic Variation, and Suicide Attempt in Bipolar Disorder
- Creators
- Aysheh Alrfooh - University of IowaLucas G Casten - University of IowaJenny Gringer Richards - University of IowaJohn A Wemmie - University of IowaVincent A Magnotta - University of IowaJess G Fiedorowicz - University of IowaJacob Michaelson - University of IowaAislinn J Williams - University of IowaMarie E Gaine - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Archives of suicide research, Vol.30(1), pp.203-223
- DOI
- 10.1080/13811118.2025.2511264
- PMID
- 40476679
- PMCID
- PMC12309415
- NLM abbreviation
- Arch Suicide Res
- ISSN
- 1543-6136
- eISSN
- 1543-6136
- Publisher
- Taylor & Francis
- Grant note
- Iowa Neuroscience Institute Research Program of Excellence
We would like to thank the study participants for their willingness to participate in the study. We would also like to thank Hsiang Wen and Benney Argue for sample collection and management of the cohort.
- Language
- English
- Electronic publication date
- 06/06/2025
- Date published
- 01/02/2026
- 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
- 9984826347702771
Metrics
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