Psychosocial moderators of polygenic risk for suicidal ideation: Results from a 7-year population-based, prospective cohort study of U.S. veterans.

Na PJ, De Angelis F, Nichter B, Wendt FR, Krystal JH, Southwick SM, Levey DF, Gelernter J, Polimanti R, Pietrzak RH. Psychosocial moderators of polygenic risk for suicidal ideation: Results from a 7-year population-based, prospective cohort study of U.S. veterans. Molecular Psychiatry. 2022 Feb 1; 27(2):1068-1074.

Related HSR&D Project(s)

• SDR 16-348 – PRIME Care (PRecision medicine In MEntal health Care)

Dimensions for VA is a web-based tool available to VA staff that enables detailed searches of published research and research projects.

If you have VA-Intranet access, click here for more information vaww.hsrd.research.va.gov/dimensions/

VA staff not currently on the VA network can access Dimensions by registering for an account using their VA email address.    Search Dimensions for VA for this citation
* Don't have VA-internal network access or a VA email address? Try searching the free-to-the-public version of Dimensions

Search for Abstract from PubMed

---

Abstract:

Polygenic risk scores (PRS) may help inform the etiology of suicidal thoughts and behaviors. In this study, we evaluated whether a suicidality PRS derived from a large genome-wide association study (GWAS) of suicidality from the UK Biobank (N? = 122,935) predicted suicidal ideation (SI) in a 7-year population-based, prospective cohort of European-American US veterans (N? = 1326). Results revealed that 8.8% (n? = 115) of veterans developed new-onset SI, 4.0% (n? = 52) had chronic SI, 3.4% (n? = 31) had remitted SI, and 83.8% (n? = 1128) denied SI over the study period. Suicidality PRS was positively associated with chronic SI (relative risk ratio [RRR]? = 4.54, 95% confidence interval [CI]? = 1.01-20.48) and new-onset SI (RRR? = 2.97, 95%CI? = 1.22-7.23), and negatively associated with remitted SI (RRR? = 0.12, 95% CI? = 0.02-0.60). Among veterans with higher suicidality PRS, those with higher baseline dispositional optimism had a lower likelihood of chronic SI (RRR? = 0.67, 95% CI? = 0.49-0.91) and higher likelihood of remitted SI (RRR? = 1.98, 95% CI? = 1.18-3.31). Among veterans with higher suicidality PRS, those with higher baseline levels of social support were less likely to develop new-onset SI (RRR? = 0.95, 95% CI? = 0.92-0.99). These interaction effects were enriched for genes implicated in neuron recognition and development, while the PRS main effect was enriched for genes involved in mannosylation. Collectively, results of this study suggest that suicidality PRS is linked prospectively to symptomatic courses of SI, and that dispositional optimism and social support moderate these associations. Interventions targeting these modifiable psychosocial factors may help mitigate risk of SI in veterans with high polygenic risk for suicidality.