Summary: New genetic research from the University of Utah suggests that many people who die by suicide without any recorded history of suicidal thoughts or behaviors form a distinct risk group rather than simply representing missed or undiagnosed cases of depression. Analysis of genetic data from more than 2,700 suicide deaths found that those without prior suicidal behavior carry fewer genetic risk factors associated with major psychiatric conditions compared with people who had documented suicidality before death.
These results challenge the widespread assumption that improved screening for depression and related disorders alone will identify most individuals at risk of suicide. The findings indicate alternative biological and environmental pathways to suicide that current prevention strategies do not adequately address.
Key facts
- A distinct risk group: Individuals who die by suicide with no prior suicidal thoughts or behaviors show lower genetic risk for several psychiatric conditions compared with those who had documented suicidality.
- Not simply hidden depression: The genetic profiles of this group suggest they are not merely undiagnosed cases of typical psychiatric illness such as major depressive disorder.
- Implications for prevention: Screening programs that focus primarily on mood disorders and psychiatric diagnoses may miss this subgroup, indicating a need for broadened approaches to suicide prevention.
Source: University of Utah
“Among friends and family of those who die by suicide, a common refrain is: ‘I didn’t know.’”
About half of suicide deaths occur in people with no documented history of suicidal thoughts, nonfatal attempts, or known psychiatric diagnoses commonly linked to suicide risk. These individuals often show no clear clinical indicators of impending danger, leaving loved ones and clinicians surprised and searching for explanations.
A new genetic study led by Hilary Coon, PhD, professor of psychiatry at the Spencer Fox Eccles School of Medicine, analyzed anonymized genetic data from over 2,700 people who died by suicide. The study found that individuals without prior suicidal behavior—referred to here as SD-N—have fewer clinical psychiatric diagnoses and fewer genetic risk factors for several neuropsychiatric conditions than those who had documented suicidal thoughts or attempts (SD-S).
“There are a lot of people out there who may be at risk of suicide where it’s not just that you’ve missed that they’re depressed, it’s likely that they’re in fact actually not depressed,” says Dr. Coon. “That is important in widening our view of who may be at risk. We need to start to think about aspects leading to risk in different ways.”
The peer-reviewed results were published in JAMA Network Open and call for rethinking prevention strategies so they can better capture diverse pathways to suicide.
Uncovering hidden risk
Prior research showed that people who die by suicide without known prior suicidality are less likely to have psychiatric diagnoses such as depression compared to those with documented suicidal behavior. The central question remained whether these individuals were simply undiagnosed—still carrying similar underlying vulnerabilities that screening could detect—or whether their risks were fundamentally different.
Coon’s team found evidence for the latter. Using polygenic scores (PGS) derived from summary statistics of published genome-wide association studies, the researchers compared genetic liabilities across SD-N and SD-S groups drawn from the Utah Suicide Mortality Research Study (cases accrued from December 1998 to October 2022) and also examined population controls.
The analysis revealed that people in the SD-N group had significantly lower polygenic scores for major depressive disorder, depressed affect, anxiety, neuroticism, Alzheimer disease, and—at a slightly less stringent threshold—posttraumatic stress disorder, compared with those who had prior suicidality. Importantly, the SD-N group’s genetic scores for some traits did not differ significantly from population controls, suggesting this subgroup does not have elevated genetic liability for the psychiatric traits commonly targeted in prevention screening.
In other words, many individuals who die by suicide without prior warning signs appear to carry a different genetic and clinical risk profile than those with known suicidality. This undermines the assumption that simply improving detection of mood disorders will reach this subgroup.
Helping those most at risk
Coon emphasizes that individual genetic risk factors have very small effects and there is no single gene or simple genetic signature that causes suicide. Environmental, social, and medical contexts are crucial contributors to suicide risk, and understanding how these factors interact with underlying biology is essential.
Future research from this group will explore other contributors that may help explain risk in the SD-N group, including chronic physical conditions such as pain, inflammatory disorders, and respiratory illnesses. The team also plans to investigate traits that may confer resilience to suicidal behavior and to define subsets of individuals at risk so that care can be targeted more effectively and specifically.
“If people have a certain type of clinical diagnosis that makes them particularly vulnerable within particular environmental contexts, they still may not ever say they’re suicidal,” Coon says. “We hope our work may help reveal traits and contexts associated with high risk so that doctors can deliver care more effectively and specifically.”
Improving identification of at-risk individuals across multiple pathways could enable more timely and appropriate interventions and ultimately save lives.
Do you need help?
Call 988 to reach a free, confidential 24/7 support line for suicidal crisis or emotional distress.
The Huntsman Mental Health Institute Crisis Care Center also offers 24/7 walk-in mental health services for adults. Additional assistance is available through local chapters of suicide prevention organizations and mental health providers.
If you are concerned about a loved one or friend, asking directly about suicide remains the single most effective intervention.
Funding
This work was supported by the National Institute of Mental Health (grants R01MH122412, R01MH123489, R01ES032028, and R01MH123619), Janssen Research & Development, the American Foundation for Suicide Prevention (grant BSG-1-005-18), the Brain & Behavior Research Foundation–National Alliance for Research on Schizophrenia and Depression (grants 28132, 28686, and 31249), and the Clark Tanner Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Key questions answered
A: The study indicates they can have fundamentally different genetic and clinical profiles from those with documented suicidality, suggesting distinct biological and environmental pathways to risk.
A: Compared with individuals who had prior suicidal thoughts or attempts, this group shows fewer genetic risk factors for depression, anxiety, PTSD, Alzheimer disease, and related traits.
A: It suggests current screening methods that focus on mood and anxiety disorders may overlook a distinct pathway to suicide, so prevention strategies should be broadened to include other clinical and environmental risk factors.
Editorial notes
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full.
- Additional context was added by editorial staff.
About this research
Author: Sophia Friesen
Source: University of Utah
Contact: Sophia Friesen – University of Utah
Image: The image is credited to Neuroscience News
Original research: Open access. “Genetic Liabilities to Neuropsychiatric Conditions in Suicide Deaths With No Prior Suicidality” by Hilary Coon et al., JAMA Network Open. DOI: 10.1001/jamanetworkopen.2025.38204
Abstract
Genetic liabilities to neuropsychiatric conditions in suicide deaths with no prior suicidality
Importance: Although a prior suicide attempt is a strong predictor of later suicide death, fewer than 10% of people who attempt suicide go on to die by suicide, and roughly 50% of suicide deaths occur without evidence of a prior attempt. Risks in this group are poorly understood.
Objective: To compare polygenic liabilities among suicide deaths without evidence of prior nonfatal suicidality (SD-N) versus those with prior suicidality (SD-S), testing earlier findings that SD-N individuals show lower clinical risk for neuropsychiatric traits.
Design, setting, and participants: In this cohort study, polygenic scores were computed using summary statistics from 12 published source studies and compared across SD-N and SD-S groups from the Utah Suicide Mortality Research Study (cases accrued between December 1998 and October 2022), with comparisons to unselected population controls. Evidence of prior suicidality was determined from diagnoses and clinical notes.
Main outcomes and measures: Differences in polygenic scores reflecting neuropsychiatric conditions were tested using analysis of covariance adjusted for sex, age, and genetic ancestry, with additional analyses by sex and by age-at-death subgroup. Data were analyzed between July 2024 and July 2025.
Results: The SD-N cohort (n = 1,337) included a larger proportion of males and an older mean age at death compared with the SD-S cohort (n = 1,432). Comparing SD-N to SD-S, SD-N showed significantly lower polygenic scores for major depressive disorder, depressed affect, anxiety, neuroticism, and Alzheimer disease, with a modestly lower score for PTSD after correction. SD-N scores for some traits did not differ significantly from population controls.
Conclusions and relevance: Suicide deaths without prior nonfatal suicidality exhibit different genetic liabilities for neuropsychiatric conditions compared with those who had prior suicidality. These differences have implications for future research and for designing prevention strategies that address multiple pathways to suicide.