Investigating the relationship between DNA methylation, genetic variation, and suicide attempt in bipolar disorder

Aysheh Alrfooh; Lucas G Casten; Jenny Gringer Richards; John A Wemmie; Vincent A Magnotta; Jess G Fiedorowicz; Jacob Michaelson; Aislinn J Williams; Marie E Gaine

doi:10.1101/2024.04.03.24305263

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Investigating the relationship between DNA methylation, genetic variation, and suicide attempt in bipolar disorder

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Investigating the relationship between DNA methylation, genetic variation, and suicide attempt in bipolar disorder

Aysheh Alrfooh, Lucas G Casten, Jenny Gringer Richards, John A Wemmie, Vincent A Magnotta, Jess G Fiedorowicz, Jacob Michaelson, Aislinn J Williams and Marie E Gaine

medRxiv : the preprint server for health sciences

Cold Spring Harbor Laboratory

04/03/2024

DOI: 10.1101/2024.04.03.24305263

PMCID: PMC11023653

PMID: 38633806

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https://doi.org/10.1101/2024.04.03.24305263View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

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 for suicidal behavior. 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. 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 suicidal behavior (N=55) and without suicidal behavior (N=51). We identified seven differentially methylated CpG sites and five differentially methylated regions between the two groups. Additionally, we found that DNA methylation changes in and were associated with lethality or number of suicide attempts. Finally, we identified three meQTLs in , , and . 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 Iowa
Lucas G Casten - University of Iowa, Psychiatry
Jenny Gringer Richards - University of Iowa, Radiology
John A Wemmie - University of Iowa, Iowa Neuroscience Institute
Vincent A Magnotta - University of Iowa, Iowa Neuroscience Institute
Jess G Fiedorowicz - University of Iowa, Psychiatry
Jacob Michaelson - University of Iowa
Aislinn J Williams - University of Iowa, Iowa Neuroscience Institute
Marie E Gaine - University of Iowa, Iowa Neuroscience Institute
Resource Type: Preprint
Publication Details: medRxiv : the preprint server for health sciences
DOI: 10.1101/2024.04.03.24305263
PMID: 38633806
PMCID: PMC11023653
Publisher: Cold Spring Harbor Laboratory; United States
Language: English
Date posted: 04/03/2024
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: 9984617010002771

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