Polygenic Risk Scores in Child and Adolescent Psychiatry: Ethical, Clinical, and Legal Implications

项目摘要 最近，超过500个与各种精神疾病相关的基因组位点，包括精神分裂症， 抑郁症和自闭症谱系障碍已经被确定。这使得生成 多基因风险评分（PRS）对不同精神疾病风险的个体进行分层， 对大众来说。作为一种预测工具，精神病PRS可能是最有价值的， 适用于发病前的个人。在大约75%的病例中， 或前驱特征在成年早期发生，使得精神病PRS可能对儿童最有用， 青少年。减贫战略有可能改善早期识别，并导致加强监测和 干预措施，以潜在地预防或延迟发病，并尽量减少发病率和自杀风险，第二， 是美国10-24岁人群的主要死因尽管他们的承诺，PRS可能特别危险 在精神病学的背景下，我们的初步工作发现，PRS已经被用于 儿童和青少年精神病学精神疾病有很大的耻辱感，并且有滥用药物的历史。 美国“不良”行为或精神疾病的“预测因子”。因此，精神病PRS可能是另一种工具 用来对付精神病患者此外，精神病PRS可以说是第一个工具， 对任何个人的精神疾病进行风险预测的能力，并且存在关键的法律的空白 在保护这一信息的隐私和防止基因歧视方面。促进 为了在儿童和青少年中负责任地使用精神病PRS，我们将使用混合方法， 包括定性、定量和法律的分析，以：1）让利益相关者发表意见（即，病人， 父母/照顾者，临床医生），通过检查他们的观点，精神病PRS是否应该 使用，如果使用，如何使用;以及2）检查法律的和监管环境，以确定可能的保障措施 必要虽然其中一些差距也适用于其他遗传信息，但我们将专注于识别 针对患有或有风险的个人可能使用和滥用精神科PRS的潜在政策解决方案 精神疾病，几乎占美国人口的30%。这项研究的长期目标是开发 道德上合理和知情的指导方针，以应对使用 儿童和青少年的精神病PRS。建立在我们的NIH资助的儿童和青少年精神病学 遗传学调查（CAPGS），调查了儿童和青少年精神科医生对PRS的看法 （3R 00 HG 008689 - 05 S1），当前提案的目的是使用混合方法设计来检查： 1)2）主要持份者对精神科PRS的看法，以及 3)在防止侵犯隐私和基于精神病PRS的歧视的法律的保护方面存在差距。

PROJECT SUMMARY Recently, more than 500 genomic loci associated with various psychiatric disorders, including schizophrenia, depression, and autism spectrum disorders, have been identified. This makes it possible to generate polygenic risk scores (PRS) to stratify individuals by risk for different psychiatric disorders compared to the general population. As a prediction tool, psychiatric PRS would likely be most valuable when applied to individuals before the onset of illness. In about 75% of cases, the onset of psychiatric disorders or prodromal features occurs by early adulthood making psychiatric PRS likely most useful for children and adolescents. PRS have the potential to improve early identification, and lead to enhanced monitoring and interventions to potentially prevent or delay onset, and minimize morbidity and risk for suicide, the second leading cause of death in the U.S. in ages 10–24. Despite their promise, PRS could be especially perilous in the context of psychiatry, and our preliminary work has found that PRS are already being used in child and adolescent psychiatry. There is significant stigma around mental illness, and a history of misuse of “predictors” of “undesirable” behaviors or mental illness in the US. Thus, psychiatric PRS could be another tool used against patients with psychiatric disorders. Further, psychiatric PRS are arguably the first tool with the capacity to generate risk predictions about psychiatric disorders for any individual and there are key legal gaps in the protection of the privacy of this information and the prevention of genetic discrimination. To promote responsible use of psychiatric PRS in children and adolescents, we will use a mixed-methods approach that includes qualitative, quantitative, and legal analysis to: 1) give voice to stakeholders (i.e., patients, parents/caregivers, clinicians) by examining their perspectives regarding whether psychiatric PRS should be used and, if so, how; and 2) examine the legal and regulatory landscape to identify what safeguards may be necessary. Although some of these gaps also apply to other genetic information, we will focus on identifying potential policy solutions for the likely uses and misuses of psychiatric PRS against individuals with or at risk of psychiatric disorders, almost 30% of the US population. The long-term goal of this research is to develop ethically-justified and empirically-informed guidelines to address the ethical challenges raised by the use of psychiatric PRS with children and adolescents. Building on our NIH-funded Child and Adolescent Psychiatric Genetics Survey (CAPGS), which examined child and adolescent psychiatrists’ perspectives about PRS (3R00HG008689-05S1), the objective of the current proposal is to use a mixed-methods design to examine: 1) challenges in the clinical use of psychiatric PRS, 2) key stakeholders’ perspectives on psychiatric PRS, and 3) gaps in legal protections against privacy violations and discrimination based on psychiatric PRS.