41 Characterizing the Effects of Mitochondrial DNA in Suicides

Objective: The purpose of this study was to investigate the role of mitochondrial DNA (mtDNA) in stress-related disorders that are associated with suicide risk. Identifying risk factors can help improve intervention methods and predict individuals who are at risk for suicide. Methods: mtDNA levels of 662 suicide cases were measured using whole genome sequence (WGS) data and cases were split into high vs. low mtDNA quartiles. Diagnostic status of major depressive disorder (MDD), post-traumatic stress disorder (PTSD) and anxiety were assessed from medical records data, and polygenic risk scores (PRS) of suicides were compared between the high and low quartiles. Results: In our initial data (N = 277), results in the highest mtDNA group for the presence/absence of diagnoses of MDD (OR = 0.83; p = 0.56) and PTSD (OR = 0.72; p = 0.64) were non-significant. Anxiety was nominally significant (OR = 0.53; p = 0.05) but lost significance after adjusting for covariate effects of sex and age (p=0.08). PRS for PTSD was significantly higher in the high mtDNA group (p=0.007) adjusting for age sex, and ancestry; there were no PRS differences for MDD or anxiety. After more than doubling the sample size (N = 622), the significant associations found initially were no longer present and no further significance was observed in other characteristics. Conclusions: These results may not be as surprising as prior studies of suicide risk factors show conflicting results. It is important to replicate results as it gives us credible evidence that clinical or genetic risks are robust and generalizable across populations. However, replication can be difficult to achieve when studying the genetic and clinical risks associated with of psychiatric conditions. Non-replication in our new data suggested that our initial results likely occurred by chance. Despite the same demographics in our newer sample, we may not see a significance due to the lack of signal in the same risk factors. Future research should further examine the patterns of mtDNA to better understand the mechanism it plays in psychiatric conditions.