Suicide attempts (SA), especially recurrent SA or serious SA, are common in substance use disorders (SUD). However, the genetic component of SA in SUD samples remains unclear. Brain-derived neurotrophic factor (BDNF) alleles and levels have been repeatedly involved in stress-related psychopathology. This investigation uses a within-cases study of BDNF and associated factors in three suicidal phenotypes (‘any’, ‘recurrent’, and ‘serious’) of outpatients seeking treatment for opiate and/or cocaine use disorder. Phenotypic characterization was ascertained using a semi-structured interview. After thorough quality control, 98 SNPs of BDNF and associated factors (the BDNF pathway) were extracted from whole-genome data, leaving 411 patients of Caucasian ancestry, who had reliable data regarding their SA history. Binary and multinomial regression with the three suicidal phenotypes were further performed to adjust for possible confounders, along with hierarchical clustering and compared to controls (N = 2504). Bayesian analyses were conducted to detect pleiotropy across the suicidal phenotypes. Among 154 (37%) ever suicide attempters, 104 (68%) reported at least one serious SA and 96 (57%) two SA or more. The median number of non-tobacco SUDs was three. The BDNF gene remained associated with lifetime SA in SNP-based (rs7934165, rs10835210) and gene-based tests within the clinical sample. rs10835210 clustered with serious SA. Bayesian analysis identified genetic correlation between ‘any’ and ‘serious’ SA regarding rs7934165. Despite limitations, ‘serious’ SA was shown to share both clinical and genetic risk factors of SA—not otherwise specified, suggesting a shared BDNF-related pathophysiology of SA in this population with multiple SUDs.

自杀未遂 (SA)，尤其是复发性 SA 或严重的 SA，在物质使用障碍 (SUD) 中很常见。然而，SUD 样本中 SA 的遗传成分仍不清楚。脑源性神经营养因子 (BDNF) 等位基因和水平已反复涉及与压力相关的精神病理学。这项调查使用了针对阿片类药物和/或可卡因使用障碍寻求治疗的门诊患者的三种自杀表型（“任何”、“复发”和“严重”）中的 BDNF 和相关因素的案例研究。使用半结构化访谈确定表型特征。经过彻底的质量控制，从全基因组数据中提取了 98 个 BDNF 和相关因子（BDNF 途径）的 SNP，留下了 411 名高加索血统患者，他们有关于其 SA 历史的可靠数据。N  = 2504)。进行贝叶斯分析以检测自杀表型的多效性。在 154 名 (37%) 曾经自杀未遂者中，104 名 (68%) 报告了至少一次严重的 SA，96 名 (57%) 报告了两次或更多的 SA。非烟草 SUD 的中位数为 3。在基于 SNP（rs7934165、rs10835210）和临床样本中基于基因的测试中，BDNF 基因仍然与寿命 SA 相关。rs10835210 与严重 SA 聚集。贝叶斯分析确定了关于 rs7934165 的“任何”和“严重”SA 之间的遗传相关性。尽管存在局限性，但“严重”SA 被证明具有 SA 的临床和遗传风险因素——未另行说明，这表明在具有多个 SUD 的人群中，SA 的共同 BDNF 相关病理生理学。