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

儿童和青少年精神病学中的多基因风险评分：伦理、临床和法律意义

• 批准号: 10483181
• 负责人: Gabriel Lazaro-Munoz
• 金额: $ 62.22万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-07 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10483181
• 关键词: 18 year old; Address; Adolescent; Adolescent Psychiatry; Adult; Age; Behavior; Biomedical Technology; Caregivers; Cause of Death; Child; Child Psychiatry; Clinical; Data; Discrimination; Disease; Early Intervention; Early identification; Ethics; Funding; Future; General Population; Generations; Genetic; Goals; Guidelines; Individual; Information Protection; Intervention; Interview; Laws; Lead; Legal; Mental Depression; Mental disorders; Methods; Minor; Monitor; Morbidity - disease rate; Onset of illness; Other Genetics; Outcome; Parents; Patients; Persons; Policies; Population; Prevention; Privacy; Psychiatric therapeutic procedure; Psychiatrist; Psychiatry; Recording of previous events; Research; Risk; Schizophrenia; Schools; Surveys; United States National Institutes of Health; Work; adolescent patient; autism spectrum disorder; base; clinical care; court; design; disability; emerging adult; ethical legal social implication; experience; genetic discrimination; genetic information; genetic testing; genomic locus; improved; innovation; legal implication; polygenic risk score; prevent; privacy protection; psychogenetics; research study; risk prediction; social; social stigma; societal costs; stakeholder perspectives; suicidal risk; tool; working group

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.

项目摘要 最近，超过500个基因组基因座与包括精神分裂症在内的各种精神疾病相关， 抑郁症和自闭症谱系障碍已被发现。这使得生成 多基因风险评分（PRS）以不同的精神疾病的风险分层 向普通人群。作为一种预测工具，精神科PR可能是最有价值的 在疾病发作之前应用于个人。在大约75％的病例中，精神疾病的发作 或前瞻性特征通过成年早期而发生，使精神病PR可能对儿童和 青少年。 PR有可能改善早期识别，并导致增强的监测和 潜在的预防或延迟发作的干预措施，并最大程度地减少自杀的发病率和风险 美国的主要死因10-24岁。尽管承诺，PR可能特别危险 在精神病学的背景下，我们的初步工作发现PR已经被用于 儿童和青少年精神病学。精神疾病和滥用的历史存在很大的污名 美国“不良行为或精神​​疾病的“预测因素”。那就是精神病学可以是另一个工具 用于精神疾病患者。此外，精神病PR可以说是第一个使用 为任何个人产生有关精神疾病的风险预测的能力，并且存在关键的法律差距 在保护该信息的隐私和预防遗传歧视方面。促进 负责在儿童和青少年中使用精神病PR，我们将使用一种混合方法方法 包括定性，定量和法律分析至：1）向利益相关者（即患者， 父母/照顾者，临床医生）检查他们关于精神病PRS是否应该是的观点 使用的以及如何使用； 2）检查法律和监管格局，以确定可能是什么保障措施 尽管其中一些差距也适用于其他遗传信息，但我们将专注于确定 潜在的政策解决方案可能使用或遇到具有或有风险的人的精神病患者 精神疾病，近30％的美国人口。这项研究的长期目标是发展 通过道德约束和经验知觉的准则，以应对使用的道德挑战 具有儿童和青少年的精神病学PR。建立我们的NIH资助的孩子和青少年精神病学 遗传学调查（CAPG），研究了儿童和青少年精神科医生对PRS的观点 （3R00HG008689-05S1），当前建议的目的是使用混合方法设计： 1）临床使用精神病PR的挑战，2）关键利益相关者对精神病PR的观点以及 3）基于精神病PRS的法律保护措施的差距。