Substance dependence diagnoses (SDs) are important risk factors for suicidality. We investigated the associations of multiple SDs with different suicidality outcomes, testing how genetic background moderates these associations. The Yale-Penn cohort (N = 15,557) was recruited to investigate the genetics of SDs. The Army STARRS (Study to Assess Risk and Resilience in Servicemembers) cohort (N = 11,236) was recruited to evaluate mental health risk and resilience among Army personnel. We applied multivariate logistic regression to investigate the associations of SDs with suicidality and, in the Yale-Penn cohort, we used the structured linear mixed model (StructLMM) to study multivariate gene–environment interactions. In Yale-Penn, lifetime polysubstance dependence was strongly associated with lifetime suicidality: having five SDs showed an association with suicidality, from odds ratio (OR) = 6.77 (95% confidence interval, CI = 5.74–7.99) for suicidal ideation (SI) to OR = 3.61 (95% CI = 2.7–4.86) for suicide attempt (SA). In Army STARRS, having multiple substance use disorders for alcohol and/or drugs was associated with increased suicidality ranging from OR = 2.88 (95% CI = 2.6–3.19) for SI to OR = 3.92 (95% CI = 3.19–4.81) for SA. In Yale-Penn, we identified multivariate gene–environment interactions (Bayes factors, BF > 0) of SI with respect to a gene cluster on chromosome 16 (LCAT, p = 1.82 × 10^–7; TSNAXIP1, p = 2.13 × 10⁻⁷; CENPT, p = 2.32 × 10⁻⁷; PARD6A, p = 5.57 × 10⁻⁷) for opioid dependence (BF = 12.2), cocaine dependence (BF = 12.1), nicotine dependence (BF = 9.2), and polysubstance dependence (BF = 2.1). Comorbidity of multiple SDs is a significant associated with suicidality and heritability of suicidality is partially moderated by multivariate gene interactions.

物质依赖诊断（SDs）是自杀的重要危险因素。我们调查了多个 SD 与不同自杀结果的关联，测试遗传背景如何调节这些关联。Yale-Penn 队列 ( N  = 15,557) 被招募来研究 SDs 的遗传学。陆军 STARRS（服役人员风险和复原力评估研究）队列 ( N = 11,236) 被招募来评估陆军人员的心理健康风险和适应能力。我们应用多变量逻辑回归来研究 SD 与自杀的关联，并且在耶鲁大学-宾夕法尼亚大学队列中，我们使用结构化线性混合模型 (StructLMM) 来研究多变量基因 - 环境相互作用。在耶鲁大学，终生多物质依赖与终生自杀倾向密切相关：5 个 SD 显示与自杀倾向相关，对于自杀意念 (SI)，优势比 (OR) = 6.77（95% 置信区间，CI = 5.74–7.99）自杀未遂 (SA) 的 OR = 3.61 (95% CI = 2.7–4.86)。在陆军 STARRS 中，因酒精和/或药物而患有多种物质使用障碍与自杀性增加有关，范围从 SI 的 OR = 2.88（95% CI = 2.6-3.19）到 SI 的 OR = 3.92（95% CI = 3.19-4.81）萨。LCAT , p  = 1.82 × 10 ^–7；TSNAXIP1，p  = 2.13 × 10 ^-7；CENPT , p  = 2.32 × 10 ^-7；PARD6A , p  = 5.57 × 10 ^-7 ) 用于阿片类药物依赖 (BF = 12.2)、可卡因依赖 (BF = 12.1)、尼古丁依赖 (BF = 9.2) 和多物质依赖 (BF = 2.1)。多个 SD 的合并症与自杀性显着相关，并且自杀性的遗传性部分受多变量基因相互作用的影响。