Despite recent progress in the genetics of suicidal behavior, the pathway by which genetic liability increases suicide attempt risk is unclear. We investigated the mediational pathways from family/genetic risk for suicide attempt (FGRS_SA) to suicide attempt by considering the roles of psychiatric illnesses. In a Swedish cohort, we evaluated time to suicide attempt as a function of FGRS_SA and the mediational effects of alcohol use disorder, drug use disorder, attention-deficit/hyperactivity disorder, major depression, anxiety disorder, bipolar disorder, and non-affective psychosis. Analyses were conducted by sex in three age periods: 15–25 years (N_females = 850,278 and N_males = 899,366), 26–35 years (N_females = 800,189 and N_males = 861,774), and 36–45 years (N_females = 498,285 and N_males = 535,831). The association between FGRS_SA and suicide attempt was mediated via psychiatric disorders. The highest mediation effects were observed for alcohol use disorder in males (15–25 years, HR_total = 1.60 [1.59; 1.62], mediation = 14.4%), drug use disorder in females (25–36 years, HR_total = 1.46 [1.44; 1.49], mediation = 11.2%), and major depression (25–36 years) in females (HR_total = 1.46 [1.44; 1.49], mediation = 7%) and males (HR_total = 1.50 [1.47;1.52], mediation = 4.7%). While the direct effect of FGRS_SA was higher at ages of 15–25, the mediation via psychiatric disorders was more prominent in later adulthood. Our study informs about the psychiatric illnesses via which genetic liability operates to impact suicide attempt risk, with distinct contributions according to age and sex.

中文翻译：

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总体遗传责任与非致命自杀企图之间的中介途径：基于瑞典人群的队列

尽管最近在自杀行为遗传学方面取得了进展，但遗传倾向增加自杀未遂风险的途径尚不清楚。我们通过考虑精神疾病的作用，研究了从自杀企图的家庭/遗传风险（FGRS _SA ）到自杀企图的中介途径。在瑞典队列中，我们评估了自杀企图时间与 FGRS _SA的函数关系以及酒精使用障碍、药物使用障碍、注意力缺陷/多动障碍、重度抑郁症、焦虑症、双相情感障碍和非情感障碍的中介作用。精神病。按性别分三个年龄阶段进行分析：15-25 岁（N_名女性 = 850,278，N名_男性 = 899,366）、26-35 岁（N_名女性 = 800,189 和N 名_男性 = 861,774）和 36-45 岁（N_名女性= 861,774）  = 498,285 名_男性=  535,831 名）。 FGRS _SA与自杀未遂之间的关联是通过精神疾病介导的。观察到男性酒精使用障碍的中介效应最高（15-25 岁，HR_总计 = 1.60 [1.59; 1.62]，中介 = 14.4%），女性吸毒障碍（25-36 岁，HR_总计 = 1.46 [女性（HR 总计 = 1.46 [1.44; 1.49]，中介 = 11.2%）和重度抑郁症（25-36 岁）（HR_总计 = 1.46 [1.44; 1.49]，中介 = 7%）和男性（HR_总计 = 1.50 [1.47;1.52] ，中介 = 4.7%）。虽然 FGRS _SA的直接影响在 15-25 岁之间较高，但通过精神疾病的调节在成年后期更为突出。我们的研究揭示了遗传倾向影响自杀未遂风险的精神疾病，并且根据年龄和性别有不同的贡献。