Genomics-driven screening for causal determinants of suicide attempt
Genomics-driven screening for causal determinants of suicide attempt
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DOI：
10.1177/00048674221091499
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发表时间：
2022-04-11
影响因子：
4.6
通讯作者：
Renteria, Miguel E.
中科院分区：
文献类型：
--
作者：
Campos, Adrian, I;Garcia-Marin, Luis M.;Renteria, Miguel E.
目的：每年约有一百万人死于自杀。尽管自杀未遂被认为是一个公共卫生问题，但关于自杀未遂风险的因果决定因素的大规模研究却很少。在这里，我们利用最近的自杀企图全基因组关联研究（GWAS）的结果，对与自杀企图有因果关系的特征进行数据驱动的筛选。研究方法：我们对自杀企图风险与1520个性状之间的因果关系进行了假设生成表型筛选，这些性状已在复杂性状基因组学虚拟实验室平台上系统地汇总。我们采用了潜在因果变量（LCV）方法，该方法使用GWAS的结果来评估因果关系是否可以解释两个性状之间的遗传相关性。如果一个性状因果地影响另一个性状，那么增加因果性状风险的遗传变异也会增加导致遗传相关性的结果的风险。尽管如此，当性状共享共同的途径时，也可以观察到遗传相关性。LCV方法可以评估两个遗传相关性状的遗传效应模式是否支持因果关联而不是共同病因。结果：我们的方法确定了62个增加自杀企图风险的特征。确定的风险因素可大致分为（1）身体健康障碍，包括食管炎，纤维肌痛，疝气和癌症;（2）与心理健康相关的特征，如抑郁症，物质使用障碍和焦虑;（3）生活方式特征，包括参与战斗或暴露于战区，以及特定的工作类别，如卡车司机或机器操作员。结论：自杀未遂风险可能是由行为表型和身体和精神疾病的风险相结合来解释的。我们的研究结果还表明，物质使用行为和疼痛相关疾病与自杀企图风险增加有关，阐明了支撑这一重大公共卫生问题的重要因果机制。
Objective: Each year, around one million people die by suicide. Despite its recognition as a public health concern, large-scale research on causal determinants of suicide attempt risk is scarce. Here, we leverage results from a recent genome-wide association study (GWAS) of suicide attempt to perform a data-driven screening of traits causally associated with suicide attempt. Methods: We performed a hypothesis-generating phenome-wide screening of causal relationships between suicide attempt risk and 1520 traits, which have been systematically aggregated on the Complex-Traits Genomics Virtual Lab platform. We employed the latent causal variable (LCV) method, which uses results from GWAS to assess whether a causal relationship can explain a genetic correlation between two traits. If a trait causally influences another one, the genetic variants that increase risk for the causal trait will also increase the risk for the outcome inducing a genetic correlation. Nonetheless, a genetic correlation can also be observed when traits share common pathways. The LCV method can assess whether the pattern of genetic effects for two genetically correlated traits support a causal association rather than a shared aetiology. Results: Our approach identified 62 traits that increased risk for suicide attempt. Risk factors identified can be broadly classified into (1) physical health disorders, including oesophagitis, fibromyalgia, hernia and cancer; (2) mental health-related traits, such as depression, substance use disorders and anxiety; and (3) lifestyle traits including being involved in combat or exposure to a war zone, and specific job categories such as being a truck driver or machine operator. Conclusions: Suicide attempt risk is likely explained by a combination of behavioural phenotypes and risk for both physical and psychiatric disorders. Our results also suggest that substance use behaviours and pain-related conditions are associated with an increased suicide attempt risk, elucidating important causal mechanisms that underpin this significant public health problem.