Objective:

More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.

Methods:

The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.

Results:

Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R²=0.25%), bipolar disorder (R²=0.24%), and schizophrenia (R²=0.40%).

Conclusions:

This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.

中文翻译：

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精神疾病中自杀企图的 GWAS 以及与重度抑郁症多基因风险评分的关联。

客观的：

超过 90% 的自杀未遂者有精神病诊断；然而，双胞胎和家庭研究表明，自杀未遂的遗传病因部分不同于精神疾病本身。作者介绍了关于自杀未遂的最大的全基因组关联研究 (GWAS)，使用来自精神病学基因组学联合会的重度抑郁症、双相情感障碍和精神分裂症患者队列。

方法：

样本包括 1,622 名自杀未遂者和 8,786 名患有严重抑郁症的未自杀者；3,264 名尝试者和 5,500 名未尝试者患有躁郁症；以及 1,683 名尝试者和 2,946 名未尝试者患有精神分裂症。通过比较每种疾病的自杀未遂者和未自杀者，进行 GWAS 研究，然后对各种疾病进行荟萃分析。多基因风险评分用于研究自杀未遂与精神疾病之间的遗传关系。

结果：

发现了三个自杀未遂的全基因组显着位点：一个与重度抑郁症的自杀未遂相关，一个与双相情感障碍的自杀未遂相关，一个与情绪障碍自杀未遂的荟萃分析有关。这些关联并未在来自 UK Biobank 和 iPSYCH 的独立情绪障碍队列中得到复制。在所有三种疾病的荟萃分析中未发现显着关联。重度抑郁症的多基因风险评分与重度抑郁症 (R ² =0.25%)、双相情感障碍 (R ² =0.24%) 和精神分裂症 (R ² =0.40%) 的自杀未遂显着相关。

结论：

这项研究提供了有关遗传关联的新信息，并证明重度抑郁症的遗传责任会增加跨精神疾病的自杀未遂风险。为增加样本量而进行的进一步合作可能有助于有力地识别遗传关联，并为自杀未遂的病因学提供生物学见解。