Suicide is the second cause of death among youths. Genetics may contribute to suicidal phenotypes and their co-occurrence in other neuropsychiatric and medical conditions. Our study aimed to investigate the association of polygenic risk scores (PRSs) for 24 neuropsychiatric, inflammatory, and cardio-metabolic traits/diseases with suicide attempt (SA) or treatment-worsening/emergent suicidal ideation (TWESI). PRSs were computed based on summary statistics of genome-wide association studies. Regression analyses were performed between PRSs and SA or TWESI in four clinical cohorts. Results were then meta-analyzed across samples, including a total of 688 patients with SA (N_eff = 2,258) and 214 with TWESI (N_eff = 785). Stratified genetic covariance analyses were performed to investigate functionally cross-phenotype PRS associations. After Bonferroni correction, PRS for major depressive disorder (MDD) was associated with SA (OR = 1.24; 95% CI = 1.11–1.38; p = 1.73 × 10⁻⁴). Nominal associations were shown between PRSs for coronary artery disease (CAD) (p = 4.6 × 10⁻³), loneliness (p = .009), or chronic pain (p = .016) and SA, PRSs for MDD or CAD and TWESI (p = .043 and p = .032, respectively). Genetic covariance between MDD and SA was shown in 86 gene sets related to drugs having antisuicidal effects. A higher genetic liability for MDD may underlie a higher SA risk. Further, but milder, possible modulatory factors are genetic risk for loneliness and CAD.

中文翻译：

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神经精神、炎症和心脏代谢特征的多基因风险评分突出了与自杀企图和治疗中出现的自杀意念可能的遗传重叠

自杀是青少年死亡的第二大原因。遗传学可能导致自杀表型及其在其他神经精神疾病和医学疾病中的共同发生。我们的研究旨在调查 24 种神经精神、炎症和心脏代谢特征/疾病的多基因风险评分 (PRS) 与自杀未遂 (SA) 或治疗恶化/紧急自杀意念 (TWESI) 的关系。PRS 是根据全基因组关联研究的汇总统计数据计算的。在四个临床队列中，在 PRS 和 SA 或 TWESI 之间进行了回归分析。然后对样本的结果进行荟萃分析，包括总共 688 名 SA 患者 ( N _eff  = 2,258) 和 214 名 TWESI ( N _eff = 785)。进行分层遗传协方差分析以研究功能上的跨表型 PRS 关联。在 Bonferroni 校正后，重度抑郁症 (MDD) 的 PRS 与 SA 相关（OR = 1.24；95% CI = 1.11–1.38；p  = 1.73 × 10 ^-4）。冠状动脉疾病 (CAD) ( p  = 4.6 × 10 ^-3 )、孤独 ( p  = .009) 或慢性疼痛 ( p  = .016) 的 PRS 与 SA、MDD 或 CAD 的 PRS 和 TWESI 之间显示名义关联( p  = .043 和p = .032，分别）。MDD 和 SA 之间的遗传协方差显示在 86 个与具有抗自杀作用的药物相关的基因组中。MDD 较高的遗传风险可能是较高 SA 风险的基础。此外，但更温和的可能调节因素是孤独和 CAD 的遗传风险。