Leveraging Family Genetic Risk Scores to Understand the Etiology of Suicidal Behaviors and Their Associations With Psychiatric Disorders

IF 4.7 2区医学 Q1 PSYCHIATRY

Acta Psychiatrica Scandinavica Pub Date : 2026-09-01 Epub Date: 2026-06-19 DOI:10.1111/acps.70117

Séverine Lannoy, Henrik Ohlsson, Mallory Stephenson, Jan Sundquist, Kristina Sundquist, Kenneth S. Kendler, Alexis C. Edwards

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Abstract

Introduction

Suicidal behaviors are complex phenotypes, often studied in the context of psychiatric comorbidities. However, little is known about the specific roles of psychiatric disorders and the etiology of suicidal behaviors that occur outside the context of psychiatric comorbidities.

Methods

We included 926,040 individuals born 1980–1990 from the Swedish national registries. We conducted separate analyses for suicide attempt (SA) and suicide death (SD) and first tested whether family genetic risk scores (FGRS) for SA and SD differed across individuals with versus without a registration for psychiatric disorders. We then performed Cox proportional hazards models to evaluate the main effects of psychiatric disorders (alcohol use disorder, major depression, anxiety disorders, drug use disorders, attention-deficit/hyperactivity disorder) in risk of SA/SD, and their interaction with genetic liability (FGRS). The interaction was introduced to evaluate potential differential effects of genetic risk in those with versus without a prior psychiatric comorbidity.

Results

Only ~30% of individuals registered for SA/SD had a prior psychiatric diagnosis. FGRS for SA/SD was higher in those with prior psychiatric disorders. All psychiatric comorbidities were significantly related to SA (HRs 4.61-9.03) and SD (HRs 8.06-15.90). Interaction analyses indicated that, in those with no prior psychiatric disorder, the effect of genetic liability on SA/SD was higher.

Conclusions

Though psychiatric disorders were associated with increased risk of SA/SD, a substantial proportion of suicidal behaviors occurred outside the context of psychiatric disorders, urging the development of screening and prevention in non-psychiatric populations. Despite their low genetic liability for SA/SD, findings suggest that the effect of genetic risk on SA/SD risk is stronger in those with no psychiatric comorbidity.

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利用家庭遗传风险评分来了解自杀行为的病因及其与精神疾病的关系。

前言：自杀行为是一种复杂的表型，通常在精神合并症的背景下研究。然而，人们对精神疾病的具体作用和发生在精神合并症之外的自杀行为的病因知之甚少。方法：我们从瑞典国家登记处纳入了926,040名1980-1990年出生的个体。我们对自杀企图（SA）和自杀死亡（SD）进行了单独的分析，并首先测试了SA和SD的家庭遗传风险评分（FGRS）在有和没有精神疾病登记的个体之间是否存在差异。然后，我们使用Cox比例风险模型来评估精神疾病（酒精使用障碍、重度抑郁症、焦虑症、药物使用障碍、注意力缺陷/多动障碍）对SA/SD风险的主要影响，以及它们与遗传倾向（FGRS）的相互作用。相互作用的引入是为了评估有或没有精神疾病共病的遗传风险的潜在差异影响。结果：只有约30%登记为SA/SD的个体有先前的精神病学诊断。先前有精神障碍者的SA/SD FGRS较高。所有精神合并症与SA （HRs 4.61 ~ 9.03）和SD （HRs 8.06 ~ 15.90）显著相关。相互作用分析表明，在没有精神障碍的人群中，遗传倾向对SA/SD的影响更高。结论：尽管精神障碍与SA/SD风险增加有关，但相当大比例的自杀行为发生在精神障碍之外，这敦促在非精神疾病人群中开展筛查和预防。尽管他们对SA/SD的遗传倾向较低，但研究结果表明，遗传风险对SA/SD风险的影响在没有精神合并症的人群中更强。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Psychiatrica Scandinavica 医学-精神病学

CiteScore

11.20

自引率

3.00%

发文量

135

审稿时长

6-12 weeks

期刊介绍： Acta Psychiatrica Scandinavica acts as an international forum for the dissemination of information advancing the science and practice of psychiatry. In particular we focus on communicating frontline research to clinical psychiatrists and psychiatric researchers. Acta Psychiatrica Scandinavica has traditionally been and remains a journal focusing predominantly on clinical psychiatry, but translational psychiatry is a topic of growing importance to our readers. Therefore, the journal welcomes submission of manuscripts based on both clinical- and more translational (e.g. preclinical and epidemiological) research. When preparing manuscripts based on translational studies for submission to Acta Psychiatrica Scandinavica, the authors should place emphasis on the clinical significance of the research question and the findings. Manuscripts based solely on preclinical research (e.g. animal models) are normally not considered for publication in the Journal.