Polygenic Prediction of Suicide: Clinical, Ethical and Psychosocial Impact

自杀是美国的主要死亡原因，也是一个主要的公共卫生问题，有数十万人自杀 每年有数以万计的人死于自杀未遂。与其他几个主要死因不同， 降低自杀率方面的进展有限，部分原因是预测能力极其有限。 哪些人会企图自杀或自杀而死。事实上，最近的一项研究的荟萃分析试图 根据假定的风险因素预测自杀发现，预测的准确性仅略高于偶然性 而且在过去的50年里没有表现出明显的进步。在这方面，近年来我们看到 人们对利用遗传信息预测自杀风险的前景越来越热情。特别是， 研究人员最近开发了多基因风险评分(PR)，它使用来自全基因组的数据 评估一个人对某一特定健康结果的相对遗传易感性的关联研究 (在这种情况下，自杀)通过聚合存在于个人基因组中的所有风险变量，按强度加权 每一个变种与相关结果的关联。早期的研究表明，用于自杀的PRS有 显著的预测能力，以及使用PRS预测个人自杀风险的前景已经产生 重大兴奋作为一种可能的精准医疗工具，用于识别需要干预和 最终防止自杀死亡。然而，也有重要的理由令人担忧。例如，如果 自杀的高比率被以宿命论的方式误解，这可能会导致患者的绝望 或过早依赖侵入性或强制性的方法来降低家庭成员的风险，以及 临床医生。低利率可能会导致错误的保证。PRS还可能影响与治疗相关的 信仰、患者与提供者的关系，以及对高危个体的污名化。拟议的研究将 调查人们对使用PRS预测自杀风险的前景和影响的态度和信念 临床护理，采用对有抑郁症状的初级保健患者的调查和定性访谈 (目标1)和初级保健医生和精神病学家(目标2)。在为患者检查的参数中 会愿意接受自杀风险的遗传预测和对收到这种预测的情绪反应 自杀倾向对自我知觉、生殖决策、生活规划的预期影响 家庭和人际关系、寻求治疗、患者-提供者关系和实际自杀 风险；以及其他可感知的风险和收益。医生将被问及感知的临床效用，并可能 对临床决策的影响，以及其他可感知的好处和风险。我们还将进行一次 医生的实验研究，检验基于PRS的自杀风险信息(即模拟)的效果 电子健康记录摘要)关于关于临床护理的假定决定(目标3)。通过调查该系统是如何 基于粗糙集的自杀预测的前景受到患者和医生的欢迎，拟议的研究将 有助于预测自杀的多基因预测的伦理、临床和社会影响。

Suicide is a leading cause of death in the U.S. and a major public health problem, with hundreds of thousands of suicide attempts and tens of thousands of deaths annually. Unlike several other leading causes of death, progress in reducing suicide rates has been limited, in part because of an extremely limited ability to predict which individuals will attempt or die by suicide. Indeed, a recent meta-analysis of studies that attempted to predict suicidality based on putative risk factors found that predictive accuracy was barely better than chance and had shown no significant improvement over five decades. In this context, recent years have seen increasing enthusiasm regarding the prospect of using genetic information to predict suicide risk. In particular, researchers have recently developed polygenic risk scores (PRS), which use data from genome-wide association studies (GWAS) to estimate a person's relative genetic susceptibility to a particular health outcome (in this case, suicide) by aggregating all risk variants present in the person's genome, weighted by the strength of each variant's association with the outcome in question. Early research suggests that PRS for suicide have significant predictive power, and the prospect of using PRS to predict individuals' risk of suicide has generated significant excitement as a possible precision medicine tool for identifying people in need of intervention and ultimately preventing suicide deaths. However, there are also significant reasons for concern. For instance, if high PRS for suicide are misinterpreted in a fatalistic manner, this could lead to hopelessness among patients or premature reliance on intrusive or coercive approaches to risk-reduction among family members and clinicians. Low PRS could potentially lead to false reassurance. PRS could also affect treatment-related beliefs, patient-provider relationships, and stigmatization of at-risk individuals. The proposed research will investigate attitudes and beliefs about the prospect and implications of using PRS to predict suicide risk in clinical care, using surveys and qualitative interviews of primary care patients with symptoms of depression (Aim 1) and of primary care physicians and psychiatrists (Aim 2). Among the parameters examined for patients will be willingness to receive genetic predictions of suicide risk and emotional reactions to the receipt of such predictions; anticipated impact of suicide PRS on self-perceptions, reproductive decision-making, life planning, familial and interpersonal relationships, treatment-seeking, patient-provider relationships, and actual suicide risk; and other perceived risks and benefits. Physicians will be asked about perceived clinical utility and likely impact on clinical decisions, along with other perceived benefits and risks. We will also conduct an experimental study of physicians, examining the effects of PRS-based suicide risk information (i.e., mock electronic health record summaries) on putative decisions about clinical care (Aim 3). By investigating how the prospect of PRS-based suicide prediction is received by patients and physicians, the proposed research will help to anticipate the ethical, clinical, and societal implications of polygenic prediction of suicide.