Suicide-related behaviors are heterogeneous and transdiagnostic, and may demonstrate varying levels of genetic overlap with different substance use disorders (SUDs). We used linkage disequilibrium score regression, genomic structural equation models, and Mendelian randomization to examine the genetic relationships between several SUDs and suicide-related behaviors. Our analyses incorporated summary statistics from the largest genome-wide association studies (GWAS) of problematic alcohol use, the Fagerström test for nicotine dependence, cannabis use disorder, and opioid use disorder (Ns ranging from 46,213–435,563) and GWAS of ever self-harmed, suicide attempt, and suicide death (Ns ranging from 18,223–117,733). We also accounted for genetic liability to depression (N = 500,199) and risk tolerance (N = 315,894). Suicide-related behaviors were significantly genetically correlated with each other and each SUD, but there was little evidence of causal relationships between the traits. Simultaneously correlating a common SUD factor with each specific suicide indicator while controlling for depression and risk tolerance revealed significant, positive genetic correlations between the SUD factor and suicide-related behaviors (r_g = 0.26–0.45, SE = 0.08–0.09). In the model, depression's association with suicide death (β = 0.42, SE = 0.06) was weaker compared to ever-self harmed and suicide attempt (β = 0.58, SE = 0.05 and β = 0.50, SE = 0.06, respectively). We identify a general level of genetic overlap between SUDs and suicide-related behaviors, which is independent of depression and risk tolerance. Additionally, our findings suggest that genetic and behavioral contributions to suicide death may somewhat differ from nonlethal suicide-related behaviors.

中文翻译：

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探索自杀相关行为和药物滥用障碍的遗传重叠


自杀相关行为具有异质性和跨诊断性，并且可能表现出与不同物质使用障碍 (SUD) 不同程度的遗传重叠。我们使用连锁不平衡评分回归、基因组结构方程模型和孟德尔随机化来检查几种 SUD 与自杀相关行为之间的遗传关系。我们的分析纳入了关于有问题的酒精使用的最大全基因组关联研究 (GWAS) 的汇总统计数据、尼古丁依赖、大麻使用障碍和阿片类药物使用障碍的 Fagerström 测试（ N s 范围为 46,213–435,563）以及曾经自我的 GWAS - 受到伤害、自杀未遂和自杀死亡（ N范围为 18,223–117,733）。我们还考虑了抑郁症的遗传倾向（ N = 500,199）和风险承受能力（ N = 315,894）。自杀相关行为彼此之间以及每个 SUD 之间均存在显着的遗传相关性，但几乎没有证据表明这些特征之间存在因果关系。同时将常见的 SUD 因素与每个特定的自杀指标相关联，同时控制抑郁和风险承受能力，揭示了 SUD 因素与自杀相关行为之间存在显着的正遗传相关性（ r _g = 0.26-0.45， SE = 0.08-0.09）。在该模型中，与曾经自残和自杀未遂（分别为β = 0.58、 SE = 0.05 和β = 0.50、 SE = 0.06）相比，抑郁症与自杀死亡的关联（ β = 0.42， SE = 0.06）较弱。我们确定了 SUD 和自杀相关行为之间遗传重叠的总体水平，这与抑郁和风险承受能力无关。 此外，我们的研究结果表明，遗传和行为对自杀死亡的影响可能与非致命性自杀相关行为有所不同。