Colbert Sarah M C, Hatoum Alexander S, Shabalin Andrey, Li Qingqin S, Coon Hilary, Nelson Elliot C, Agrawal Arpana, Docherty Anna R, Johnson Emma C
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Am J Med Genet B Neuropsychiatr Genet. 2021 Dec;186(8):445-455. doi: 10.1002/ajmg.b.32880. Epub 2021 Nov 25.
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 = 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.
与自杀相关的行为具有异质性且跨越多种诊断范畴，并且可能与不同的物质使用障碍（SUDs）表现出不同程度的基因重叠。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方法来研究几种物质使用障碍与自杀相关行为之间的基因关系。我们的分析纳入了来自最大规模的全基因组关联研究（GWAS）的汇总统计数据，这些研究涉及问题性饮酒、尼古丁依赖的法格斯特罗姆测试、大麻使用障碍和阿片类药物使用障碍（样本量从46,213至435,563），以及曾经自我伤害、自杀未遂和自杀死亡的全基因组关联研究（样本量从18,223至117,733）。我们还考虑了抑郁症的遗传易感性（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与每种物质使用障碍都存在显著的基因相关性，但几乎没有证据表明这些特征之间存在因果关系。在控制抑郁症和风险承受能力的同时，将一个共同的物质使用障碍因素与每个特定的自杀指标进行相关性分析，结果显示物质使用障碍因素与自杀相关行为之间存在显著的正基因相关性（r = 0.26 - 0.45，标准误 = 0.08 - 0.09）。在该模型中，与曾经自我伤害和自杀未遂相比，抑郁症与自杀死亡的关联较弱（β = 0.42，标准误 = 0.06；曾经自我伤害和自杀未遂的β值分别为0.58，标准误 = 0.05和β = 0.50，标准误 = 0.06）。我们确定了物质使用障碍与自杀相关行为之间存在一般水平的基因重叠，这与抑郁症和风险承受能力无关。此外，我们的研究结果表明，基因和行为对自杀死亡的影响可能与非致命性自杀相关行为略有不同。
