Contributions of PTSD polygenic risk and environmental stress to suicidality in preadolescents
Year: 2021
Type: article
Abstract: Suicidal ideation and attempts (i.e., suicidality) are complex behaviors driven by environmental stress, genetic susceptibility, and their interaction. Preadolescent suicidality is a major health problem with rising rates, yet its underlying biology is understudied. Here we studied effects of genetic stress susceptibility, approximated by the polygenic risk score (PRS) for post-traumatic-stress-disorder (PTSD), on preadolescent suicidality in participants from the Adolescent Brain Cognitive Development (ABCD) Study®. We further evaluated PTSD-PRS effects on suicidality in the presence of environmental stressors that are established suicide risk factors. Analyses included both European and African ancestry participants using PRS calculated based on summary statistics from ancestry-specific genome-wide association studies. In European ancestry participants (N = 4,619, n = 378 suicidal), PTSD-PRS was associated with preadolescent suicidality (odds ratio [OR] = 1.12, 95%CI 1-1.25, p = 0.038). Results in African ancestry participants (N = 1,334, n = 130 suicidal) showed a similar direction but were not statistically significant (OR = 1.21, 95%CI 0.93-1.57, p = 0.153). Sensitivity analyses using non-psychiatric polygenic score for height and using cross-ancestry PTSD-PRS did not reveal any association with suicidality, supporting the specificity of the association of ancestry-specific PTSD-PRS with suicidality. Environmental stressors were robustly associated with suicidality across ancestries with moderate effect size for negative life events and family conflict (OR 1.27-1.6); and with large effect size (OR ∼ 4) for sexual-orientation discrimination. When combined with environmental factors, PTSD-PRS showed marginal additive effects in explaining variability in suicidality, with no evidence for G × E interaction. Results support use of cross-phenotype PRS, specifically stress-susceptibility, as a genetic marker for suicidality risk early in the lifespan.
Source: Neurobiology of Stress
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: gold
Estimated APC paid: $3,290
Awards: Predicting suicide attempt in youth by integrating EHR, clinical, cognitive and imaging data, Mechanisms of resilience to developmental stress in children and adolescents., G3861346131, Integrating neuroimaging and brain gene expression for functional characterization of psychiatric GWAS, 9/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U MICHIGAN, 20/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT VCU, 3/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U MINNESOTA, 4/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT FIU, 7/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT YALE, 17/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UCLA, 15/21 ABCD-USA Consortium: Research Project Site at LIBR, 16/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UNIVERSITY OF ROCHESTER, 8/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT CHLA, ABCD-USA Consortium: Coordinating Center, 6/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT OHSU, 10/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT SRI, 12/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U PITTSBURGH, 19/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UVM, 1/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U UTAH, 11/21 ABCD-USA Consortium: Research Project Site at UWM, ABCD-USA Consortium: Data Analysis, Informatics and Resource Center, 21/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT WUSTL, 13/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT MUSC, 5/21 ABCD-USA Consortium: Research Project Site at UC San Diego, 18/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT THE UNIVERSITY OF FLORIDA, 2/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UMB, 14/21 ABCD-USA Consortium: Research Project Site at CU Boulder
OpenAlex ID: W3210879466