Educational attainment reduces the risk of suicide attempt among individuals with and without psychiatric disorders independent of cognition: a bidirectional and multivariable Mendelian randomization study with more than 815,000 participants.
Educational attainment reduces the risk of suicide attempt among individuals with and without psychiatric disorders independent of cognition: a bidirectional and multivariable Mendelian randomization study with more than 815,000 participants.
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DOI：
10.1038/s41398-020-01047-2
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发表时间：
2020-11-09
影响因子：
6.8
通讯作者：
Lohoff FW
中科院分区：
文献类型：
--
作者：
Rosoff DB;Kaminsky ZA;McIntosh AM;Davey Smith G;Lohoff FW
在美国，自杀行为的发生率正在上升，确定因果风险因素仍然是公共卫生的优先事项。观察性文献表明，教育程度（EA）和认知能力（CP）影响自杀未遂风险;然而，这些关系的因果关系尚不清楚。使用来自EA、CP和自杀未遂风险的全基因组关联研究（GWAS）的汇总统计数据，我们进行了多变量孟德尔随机化（MR），以解开EA和CP对自杀未遂的影响，该研究共有超过815，000名欧洲血统的白色参与者。在单变量MR（SVMR）中，EA和CP似乎降低了自杀企图风险（EA比值比（OR）/标准差（SD）增加EA（4.2年），0.524，95%CI，0.412-0.666，P = 1.07 × 10−7; CP OR每SD标准化评分增加，0.714，95%CI，0.577-0.885，P = 0.002）。相反，双向分析发现自杀企图对EA或CP没有影响。使用各种多变量MR（MVMR）模型，EA似乎是自杀未遂风险的主要危险因素，具有独立效应（OR，0.342，95%CI，0.206-0.568，P = 1.61 × 10−4），而CP无影响（OR，1.182，95%CI，0.842-1.659，P = 0.333）。在额外的MVMR分析中，同时考虑了潜在的行为和精神介质（吸烟;饮酒;和自我报告的神经，紧张，焦虑或抑郁），EA的影响几乎没有变化（OR，0.541，95%CI，0.421-0.696，P = 3.33 × 10−6）。互补MR方法的结果的一致性，适应不同的假设遗传多效性加强因果推理。我们的研究结果表明，即使考虑到精神疾病和行为介质，EA，而不是CP，可能会影响欧洲血统的白色个体的自杀未遂风险，这可能对旨在降低自杀率上升的卫生政策和计划具有重要意义。未来的工作是必要的，以检查EA自杀关系人群的不同种族。
Rates of suicidal behavior are increasing in the United States and identifying causal risk factors continues to be a public health priority. Observational literature has shown that educational attainment (EA) and cognitive performance (CP) influence suicide attempt risk; however, the causal nature of these relationships is unknown. Using summary statistics from genome-wide association studies (GWAS) of EA, CP, and suicide attempt risk with > 815,000 combined white participants of European ancestry, we performed multivariable Mendelian randomization (MR) to disentangle the effects of EA and CP on attempted suicide. In single-variable MR (SVMR), EA and CP appeared to reduce suicide attempt risk (EA odds ratio (OR) per standard deviation (SD) increase in EA (4.2 years), 0.524, 95% CI, 0.412–0.666, P = 1.07 × 10−7; CP OR per SD increase in standardized score, 0.714, 95% CI, 0.577–0.885, P = 0.002). Conversely, bidirectional analyses found no effect of a suicide attempt on EA or CP. Using various multivariable MR (MVMR) models, EA seems to be the predominant risk factor for suicide attempt risk with the independent effect (OR, 0.342, 95% CI, 0.206–0.568, P = 1.61 × 10−4), while CP had no effect (OR, 1.182, 95% CI, 0.842–1.659, P = 0.333). In additional MVMR analyses accounting simultaneously for potential behavioral and psychiatric mediators (tobacco smoking; alcohol consumption; and self-reported nerves, tension, anxiety, or depression), the effect of EA was little changed (OR, 0.541, 95% CI, 0.421–0.696, P = 3.33 × 10−6). Consistency of results across complementary MR methods accommodating different assumptions about genetic pleiotropy strengthened causal inference. Our results show that even after accounting for psychiatric disorders and behavioral mediators, EA, but not CP, may causally influence suicide attempt risk among white individuals of European ancestry, which could have important implications for health policy and programs aimed at reducing the increasing rates of suicide. Future work is necessary to examine the EA–suicide relationship populations of different ethnicities.
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