Suicide is a major public health problem. The contribution of common genetic variants for major depressive disorder (MDD) independent of personal and parental history of MDD has not been established. Polygenic risk score (using PRS-CS) for MDD was calculated for US Army soldiers of European ancestry. Associations between polygenic risk for MDD and lifetime suicide attempt (SA) were tested in models that also included parental or personal history of MDD. Models were adjusted for age, sex, tranche (where applicable), and 10 principal components reflecting ancestry. In the first cohort, 417 (6.3%) of 6,573 soldiers reported a lifetime history of SA. In a multivariable model that included personal [OR = 3.83, 95% CI:3.09–4.75] and parental history of MDD [OR = 1.43, 95% CI:1.13–1.82 for one parent and OR = 1.64, 95% CI:1.20–2.26 for both parents), MDD PRS was significantly associated with SA (OR = 1.22 [95% CI:1.10–1.36]). In the second cohort, 204 (4.2%) of 4,900 soldiers reported a lifetime history of SA. In a multivariable model that included personal [OR = 3.82, 95% CI:2.77–5.26] and parental history of MDD [OR = 1.42, 95% CI:0.996–2.03 for one parent and OR = 2.21, 95% CI:1.33–3.69 for both parents) MDD PRS continued to be associated (at p = .0601) with SA (OR = 1.15 [95% CI:0.994–1.33]). A soldier's PRS for MDD conveys information about likelihood of a lifetime SA beyond that conveyed by two predictors readily obtainable by interview: personal or parental history of MDD. Results remain to be extended to prospective prediction of incident SA. These findings portend a role for PRS in risk stratification for suicide attempts.

中文翻译：

---

重度抑郁症的多基因风险与美国士兵一生的自杀未遂有关，与重度抑郁症的个人和父母史无关

自杀是一个重大的公共卫生问题。独立于 MDD 的个人和父母病史的常见遗传变异对重度抑郁症 (MDD) 的贡献尚未确定。为欧洲血统的美国陆军士兵计算了 MDD 的多基因风险评分（使用 PRS-CS）。MDD 的多基因风险与终生自杀未遂 (SA) 之间的关联在模型中进行了测试，该模型还包括父母或个人的 MDD 病史。模型针对年龄、性别、等级（如适用）和反映血统的 10 个主要成分进行了调整。在第一队列中，6,573 名士兵中有 417 名 (6.3%) 报告了 SA 的终生病史。在一个多变量模型中，包括个人 [OR = 3.83, 95% CI:3.09–4.75] 和父母的 MDD 病史 [OR = 1.43, 95% CI:1.13–1.82 对于一位父母和 OR = 1.64, 95% CI:1.20 –2.26（父母双方），MDD PRS 与 SA 显着相关 (OR = 1.22 [95% CI:1.10–1.36])。在第二队列中，4,900 名士兵中有 204 名 (4.2%) 报告了 SA 的终生病史。在一个多变量模型中，包括个人 [OR = 3.82，95% CI：2.77–5.26] 和父母的 MDD 病史 [OR = 1.42，95% CI：0.996–2.03 对于一位父母和 OR = 2.21，95% CI：1.33父母双方 –3.69）MDD PRS 继续相关（在p  = .0601) 与 SA (OR = 1.15 [95% CI:0.994–1.33])。一名士兵的 MDD PRS 传达了关于终生 SA 的可能性的信息，超出了通过采访很容易获得的两个预测因素所传达的信息：MDD 的个人或父母历史。结果仍有待扩展到事件 SA 的前瞻性预测。这些发现预示着 PRS 在自杀未遂风险分层中的作用。