Background

Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.

Methods

We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.

Results

Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.

Conclusions

Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

中文翻译：

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剖析自杀未遂、精神疾病和已知危险因素的共同遗传结构

背景

自杀是全世界死亡的主要原因，而非致命自杀企图的发生频率要高得多，是造成残疾以及社会和经济负担的主要原因。两者都有大量的遗传病因，与相关的精神疾病部分相同，部分不同。

方法

我们对国际自杀遗传学联盟 (ISGC) 的 29,782 例自杀未遂 (SA) 病例和 519,961 例对照进行了全基因组关联研究 (GWAS)。SA 的 GWAS 以精神疾病为条件，通过基于多特征的条件和联合分析使用 GWAS 摘要统计，以消除精神疾病介导的对 SA 的遗传影响。我们研究了 SA、精神疾病和其他已知危险因素的共同和不同的遗传结构。

结果

两个基因座对 SA 具有全基因组意义：主要组织相容性复合体和 7 号染色体上的基因间基因座，后者在精神疾病调节后仍与 SA 相关，并在百万退伍军人计划的独立队列中复制。该位点与冒险行为、吸烟和失眠有关。SA与精神疾病，特别是重度抑郁症，以及吸烟、疼痛、冒险行为、睡眠障碍、较低的教育程度、生殖特征、较低的社会经济地位和较差的总体健康状况具有很强的遗传相关性。在对精神疾病进行调节后，SA与精神疾病之间的遗传相关性降低，而那些具有非精神疾病特征的基因相关性基本保持不变。

结论

我们的结果确定了一个比其他表型对 SA 影响更大的风险位点，并表明 SA 与已知的非精神疾病介导的风险因素之间存在共同的基础生物学。