A Brisbane twin study has found that suicidal thoughts and behaviours are markedly heritable, with estimates of genetic influence ranging from 51% to 80%, substantially higher than the 39% to 41% estimated for major depressive disorder. The researchers also found that environmental factors contributing to depression were largely distinct from those shaping suicidal thoughts and behaviours.
Suicidal thoughts and behaviours cover a spectrum from ideation to planning, attempts and deaths. While major depressive disorder is a strong risk factor, suicide risk cannot be explained by depression alone.
Twin and family studies indicate that suicidal thoughts and behaviours 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.
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 behaviours. They focused on three aspects of suicidal thoughts and behaviours: suicidal ideation, suicide plans, and suicide attempts. They hypothesised that polygenic risk scores for suicide attempts and major depression would explain a small amount of variation in self-reported suicidal thoughts and behaviours. These researchers also aimed to explore how much the genetic risk factors for the three aspects of suicidal thoughts and behaviours overlap.
Study authors analysed 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 behaviours and from a genome-wide association study 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 behaviours 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 behaviours. The three types of suicidal thoughts and behaviours were strongly genetically correlated with each other, and they showed a moderate genetic correlation with major depressive disorder.
Interestingly, non-shared environmental factors contributing to the diagnosis of major depressive disorder were largely distinct from those influencing suicidal thoughts and behaviours.
“This study provided compelling evidence for shared genetic architecture between DSM-IV MDD and STBs. The MD PRS demonstrated more consistent prediction of MDD compared to the SB PRS, 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 behaviours and depression. However, the authors note that they jointly analysed 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.
