An analysis of the Brisbane Longitudinal Twin Study data found moderate associations between genetic risk factors for suicidal thoughts and behaviors and major depressive disorder. However, environmental factors contributing to major depressive disorder were largely distinct from those contributing to suicidal thoughts and behaviors. The paper was published in Behavior Genetics.
Suicidal thoughts and behaviors are a major public health problem. They include suicidal ideation (i.e., thinking about suicide), planning suicide, suicide attempts, and suicide deaths. Major depressive disorder is one of the strongest known risk factors for suicidal behavior, although suicide risk cannot be explained by depression alone.
Twin and family studies indicate that suicidal thoughts and behaviors are partly heritable, suggesting that genetic differences contribute to individual vulnerability. Large genetic studies have identified many common genetic variants associated with suicide-related outcomes, but each variant contributes only a very small amount of risk. Researchers therefore increasingly use polygenic risk scores, which combine information across large numbers of genetic variants to estimate an individual’s inherited susceptibility.
Polygenic scores for both major depression and suicidal behavior have shown modest associations with suicide-related outcomes in previous studies. The genetic overlap between suicidal behavior and psychiatric disorders suggests that some of the same biological vulnerabilities may contribute to several different forms of psychopathology. At the same time, some people who experience suicidal thoughts or engage in suicidal behavior have no clear history of psychiatric disorders, indicating that additional genetic, psychological, and environmental pathways must also be involved.
With this in mind, study author Nathan A. Gillespie and his colleagues explored the contribution of polygenic risk scores for major depression and suicide attempt to suicidal thoughts and behaviors. They focused on three aspects of suicidal thoughts and behaviors: suicidal ideation, suicide plans, and suicide attempts. They hypothesized that polygenic risk scores for suicide attempts and major depression would explain a small amount of variation in self-reported suicidal thoughts and behaviors. These researchers also aimed to explore how much the genetic risk factors for the three aspects of suicidal thoughts and behaviors overlap.
Study authors analyzed data from the ongoing Brisbane Longitudinal Twin Study (BLTS). While this overall study was launched in 1992 and included over 7,000 young adult twins, siblings, and parents of European ancestry, this specific analysis focused on a subset of 2,876 participants. Assessments were carried out when twins were 12, 14, 16, 21, and 25 years old.
These analyses used data on participants’ self-reported suicidal behaviors and from a genome-wide association study (GWAS)—a study that scans the genomes of many people to find genetic variations associated with a particular disease or trait—conducted in the scope of this program. Study authors created two polygenic risk scores, one for major depression and one for suicide attempts, based on summary statistics from two large previous studies.
The results showed that the heritability of suicidal behaviors was estimated to be between 51% and 80%. This was much higher than the estimated heritability of major depressive disorder (39% to 41%). The polygenic risk score for major depression had more consistent associations with the diagnosis of major depressive disorder, while both polygenic risk scores had modest associations with suicidal behaviors. The three types of suicidal thoughts and behaviors were strongly genetically correlated with each other, and they showed a moderate genetic correlation with major depressive disorder.
Interestingly, non-shared environmental factors (unique individual experiences rather than shared family environments) contributing to the diagnosis of major depressive disorder were largely distinct from those influencing suicidal thoughts and behaviors.
“This study provided compelling evidence for shared genetic architecture between DSM-IV MDD [major depressive disorder diagnosis] and STBs [suicidal thoughts and behavior]. The MD PRS [polygenic risk score for major depression] demonstrated more consistent prediction of MDD [major depressive disorder] compared to the SB PRS [polygenic risk score for suicide attempts], though both showed modest correlations with suicide outcomes,” the study authors concluded.
The study contributes to the scientific understanding of the genetic bases of suicidal behaviors and depression. However, study authors note that they jointly analyzed data from men and women, potentially leaving some sex differences in genetic architecture unaccounted for.
The paper, “Genetic Overlap Between DSM-IV Major Depressive Disorder and Suicidal Behaviors: Evidence from Polygenic Risk Scores in Young Adult Twins,” was authored by Nathan A. Gillespie, Mei-Hsin Su, Séverine Lannoy, Mallory Stephenson, Miguel E. Rentería, Zuriel Ceja, Ian B. Hickie, Nicholas G. Martin, and Alexis C. Edwards.