Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan.
Department of General Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
Psychol Med. 2024 Feb;54(3):488-494. doi: 10.1017/S0033291723002015. Epub 2023 Aug 10.
Suicide attempts are a moderately heritable trait, and genetic correlations with psychiatric and related intermediate phenotypes have been reported. However, as several mental disorders as well as major depressive disorder (MDD) are strongly associated with suicide attempts, these genetic correlations could be mediated by psychiatric disorders. Here, we investigated genetic correlations of suicide attempts with psychiatric and related intermediate phenotypes, with and without adjusting for mental disorders.
To investigate the genetic correlations, we utilized large-scale genome-wide association study summary statistics for suicide attempts (with and without adjusting for mental disorders), nine psychiatric disorders, and 15 intermediate phenotypes.
Without adjusting for mental disorders, suicide attempts had significant positive genetic correlations with risks of attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorder, MDD, anxiety disorders and posttraumatic stress disorder; higher risk tolerance; earlier age at first sexual intercourse, at first birth and at menopause; higher parity; lower childhood IQ, educational attainment and cognitive ability; and lower smoking cessation. After adjusting for mental disorders, suicide attempts had significant positive genetic correlations with the risk of MDD; earlier age at first sexual intercourse, at first birth and at menopause; and lower educational attainment. After adjusting for mental disorders, most of the genetic correlations with psychiatric disorders were decreased, while several genetic correlations with intermediate phenotypes were increased.
These findings highlight the importance of considering mental disorders in the analysis of genetic correlations related to suicide attempts and suggest that susceptibility to MDD, reproductive behaviors, and lower educational levels share a genetic basis with suicide attempts after adjusting for mental disorders.
自杀未遂是一种中度遗传的特征，并且已经报道了与精神疾病和相关中间表型的遗传相关性。然而，由于几种精神障碍以及重度抑郁症（MDD）与自杀未遂密切相关，这些遗传相关性可能由精神障碍介导。在这里，我们研究了自杀未遂与精神疾病和相关中间表型的遗传相关性，同时调整和不调整精神障碍。
为了研究遗传相关性，我们利用了自杀未遂（调整和不调整精神障碍）、九种精神障碍和 15 种中间表型的大规模全基因组关联研究汇总统计数据。
不调整精神障碍时，自杀未遂与注意缺陷/多动障碍、精神分裂症、双相情感障碍、MDD、焦虑症和创伤后应激障碍的风险、更高的风险容忍度、首次性行为、首次生育和绝经年龄更早、更高的生育次数、更低的儿童智商、教育程度和认知能力以及更低的戒烟率有显著的正遗传相关性。调整精神障碍后，自杀未遂与 MDD 的风险、首次性行为、首次生育和绝经年龄更早以及教育程度更低有显著的正遗传相关性。调整精神障碍后，与精神障碍相关的大多数遗传相关性降低，而与中间表型相关的几个遗传相关性增加。
这些发现强调了在分析与自杀未遂相关的遗传相关性时考虑精神障碍的重要性，并表明在调整精神障碍后，MDD、生殖行为和较低的教育水平与自杀未遂具有共同的遗传基础。
