Suicide accounts for >800,000 deaths annually worldwide; prevention is an urgent public health issue. Identification of risk factors remains challenging due to complexity and heterogeneity. The study of suicide deaths with increased extended familial risk provides an avenue to reduce etiological heterogeneity and explore traits associated with increased genetic liability. Using extensive genealogical records, we identified high-risk families where distant relatedness of suicides implicates genetic risk. We compared phenotypic and polygenic risk score (PRS) data between suicides in high-risk extended families (high familial risk (HFR), n = 1,634), suicides linked to genealogical data not in any high-risk families (low familial risk (LFR), n = 147), and suicides not linked to genealogical data with unknown familial risk (UFR, n = 1,865). HFR suicides were associated with lower age at death (mean = 39.34 years), more suicide attempts, and more PTSD and trauma diagnoses. For PRS tests, we included only suicides with >90% European ancestry and adjusted for residual ancestry effects. HFR suicides showed markedly higher PRS of suicide death (calculated using cross-validation), supporting specific elevation of genetic risk of suicide in this subgroup, and also showed increased PRS of PTSD, suicide attempt, and risk taking. LFR suicides were substantially older at death (mean = 49.10 years), had fewer psychiatric diagnoses of depression and pain, and significantly lower PRS of depression. Results suggest extended familiality and trauma/PTSD may provide specificity in identifying individuals at genetic risk for suicide death, especially among younger ages, and that LFR of suicide warrants further study regarding the contribution of demographic and medical risks.

中文翻译：

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自杀死亡的大家族风险与死亡年龄较小和多基因自杀风险升高有关

全世界每年有超过 800,000 人死于自杀；预防是一个紧迫的公共卫生问题。由于复杂性和异质性，识别风险因素仍然具有挑战性。对自杀死亡与扩大家族风险增加的研究提供了减少病因异质性和探索与增加的遗传责任相关的特征的途径。使用广泛的家谱记录，我们确定了高风险家庭，其中自杀的远亲关系涉及遗传风险。我们比较了高风险大家庭自杀（高家族风险 (HFR)，n  = 1,634）、与家谱数据相关的自杀（不在任何高风险家庭（低家族风险 (LFR) ), ñ = 147)，以及与家族风险未知的家谱数据无关的自杀（UFR，n = 1,865）。HFR 自杀与较低的死亡年龄（平均 = 39.34 岁）、更多的自杀企图以及更多的 PTSD 和创伤诊断有关。对于 PRS 测试，我们仅包括具有 >90% 欧洲血统的自杀者，并针对残余血统效应进行了调整。HFR 自杀显示显着更高的自杀死亡 PRS（使用交叉验证计算），支持该亚组自杀遗传风险的特定升高，并且还显示 PTSD、自杀企图和冒险行为的 PRS 增加。LFR 自杀者死亡时的年龄要大得多（平均年龄 = 49.10 岁），抑郁症和疼痛的精神病学诊断较少，抑郁症的 PRS 显着较低。结果表明，大家庭和创伤/创伤后应激障碍可能会在识别有自杀死亡遗传风险的个体方面提供特异性，尤其是在年轻人中，