Investigating the Relationship Between DNA Methylation, Genetic Variation, and Suicide Attempt in Bipolar Disorder

Area of Science:

• Genetics
• Neuroscience
• Molecular Biology

Background:

• Individuals with bipolar disorder face a heightened risk of suicide, influenced by biological, clinical, and environmental factors.
• DNA modifications, particularly common genetic variations and DNA methylation changes, are key biological components linked to increased suicide attempt risk.
• The interaction between genetic predisposition and DNA methylation is increasingly recognized in genetic research.

Purpose of the Study:

• To investigate whether DNA methylation patterns are altered in specific gene loci associated with suicide in individuals with bipolar disorder and a history of suicide attempts.
• To test the hypothesis that epigenetic modifications play a role in the biological underpinnings of suicide attempts in bipolar disorder.

Main Methods:

• Literature review to identify 34 common genetic variants previously associated with suicidal behaviors in bipolar disorder.
• Development of a custom sequencing panel targeting relevant genomic loci.
• Profiling of DNA methylation patterns in blood samples from bipolar disorder patients with (N=55) and without (N=51) a history of suicide attempts.

Main Results:

• Identification of seven differentially methylated CpG sites and five differentially methylated regions between the groups.
• Association of DNA methylation changes in the MIF and CACNA1C genes with suicide attempt lethality or frequency.
• Discovery of three methylation-quantitative trait loci (meQTLs) in the SIRT1, IMPA2, and INPP1 genes.

Conclusions:

• DNA methylation is demonstrably altered in individuals with bipolar disorder who have a history of suicide attempts.
• These alterations occur in genomic regions previously identified as harboring suicide-related genetic variants.
• The findings underscore the role of epigenetic modifications in the biological pathways associated with suicide attempts in bipolar disorder.