Polygenic risk for suicide attempt is associated with lifetime suicide attempt in US soldiers independent of parental risk

Murray B Stein; Sonia Jain; Santiago Papini; Laura Campbell-Sills; Karmel W Choi; Brian Martis; Xiaoying Sun; Feng He; Erin B Ware; James A Naifeh; Pablo A Aliaga; Tian Ge; for International Suicide Genetics Consortium; for MVP Suicide Exemplar Workgroup; for VA Million Veteran Program; for Suicide Working Group of the Psychiatric Genomics Consortium; Jordan W Smoller; Joel Gelernter; Ronald C Kessler; Robert J Ursano

doi:10.1016/j.jad.2024.01.254

Polygenic risk for suicide attempt is associated with lifetime suicide attempt in US soldiers independent of parental risk

J Affect Disord. 2024 Apr 15:351:671-682. doi: 10.1016/j.jad.2024.01.254. Epub 2024 Feb 1.

Authors

Murray B Stein¹, Sonia Jain², Santiago Papini³, Laura Campbell-Sills⁴, Karmel W Choi⁵, Brian Martis⁶, Xiaoying Sun², Feng He², Erin B Ware⁷, James A Naifeh⁸, Pablo A Aliaga⁸, Tian Ge⁵; for International Suicide Genetics Consortium; for MVP Suicide Exemplar Workgroup; for VA Million Veteran Program; for Suicide Working Group of the Psychiatric Genomics Consortium; Jordan W Smoller⁵, Joel Gelernter⁹, Ronald C Kessler¹⁰, Robert J Ursano⁸

Affiliations

¹ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; VA San Diego Healthcare System, San Diego, CA, USA; Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, CA, USA. Electronic address: mstein@health.ucsd.edu.
² Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, CA, USA.
³ Department of Psychology, University of Hawai'i at Mānoa, Honolulu, HI, USA.
⁴ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
⁵ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁶ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; VA San Diego Healthcare System, San Diego, CA, USA.
⁷ Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
⁸ Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
⁹ Departments of Psychiatry, Genetics, and Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
¹⁰ Department of Health Care Policy, Harvard Medical School, Boston, MA, USA.

PMID: 38309480
DOI: 10.1016/j.jad.2024.01.254

Abstract

Background: Suicide is a leading cause of death worldwide. Whereas some studies have suggested that a direct measure of common genetic liability for suicide attempts (SA), captured by a polygenic risk score for SA (SA-PRS), explains risk independent of parental history, further confirmation would be useful. Even more unsettled is the extent to which SA-PRS is associated with lifetime non-suicidal self-injury (NSSI).

Methods: We used summary statistics from the largest available GWAS study of SA to generate SA-PRS for two non-overlapping cohorts of soldiers of European ancestry. These were tested in multivariable models that included parental major depressive disorder (MDD) and parental SA.

Results: In the first cohort, 417 (6.3 %) of 6573 soldiers reported lifetime SA and 1195 (18.2 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.26, 95%CI:1.13-1.39, p < 0.001] per standardized unit SA-PRS]. In the second cohort, 204 (4.2 %) of 4900 soldiers reported lifetime SA, and 299 (6.1 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.20, 95%CI:1.04-1.38, p = 0.014]. A combined analysis of both cohorts yielded similar results. In neither cohort or in the combined analysis was SA-PRS significantly associated with NSSI.

Conclusions: PRS for SA conveys information about likelihood of lifetime SA (but not NSSI, demonstrating specificity), independent of self-reported parental history of MDD and parental history of SA.

Limitations: At present, the magnitude of effects is small and would not be immediately useful for clinical decision-making or risk-stratified prevention initiatives, but this may be expected to improve with further iterations. Also critical will be the extension of these findings to more diverse populations.

Keywords: Genetics; Non-suicidal self-injury; Polygenic risk; Suicide; Suicide attempt.

Published by Elsevier B.V.

MeSH terms

Depressive Disorder, Major* / epidemiology
Depressive Disorder, Major* / genetics
Humans
Military Personnel*
Parents
Risk Factors
Self-Injurious Behavior* / epidemiology
Self-Injurious Behavior* / genetics
Suicidal Ideation
Suicide, Attempted