Department of Health Behavior & Health Education, University of Michigan School of Public Health, 1415 Washington Heights, SPH I Building, Room 3854, Ann Arbor, MI 48109, USA.
Prog Neurobiol. 2013 Nov;110:89-101. doi: 10.1016/j.pneurobio.2013.02.005. Epub 2013 Apr 9.
As the genetics of neurodegenerative disease become better understood, opportunities for genetic susceptibility testing for at-risk individuals will increase. Such testing raises important ethical and practice issues related to test access, informed consent, risk estimation and communication, return of results, and policies to prevent genetic discrimination. The advent of direct-to-consumer genetic susceptibility testing for various neurodegenerative disorders (including Alzheimer's disease (AD), Parkinson's disease, and certain prion diseases) means that ethical and practical challenges must be faced not only in traditional research and clinical settings, but also in broader society. This review addresses several topics relevant to the development and implementation of genetic susceptibility tests across research, clinical, and consumer settings; these include appropriate indications for testing, the implications of different methods for disclosing test results, clinical versus personal utility of risk information, psychological and behavioral responses to test results, testing of minors, genetic discrimination, and ethical dilemmas posed by whole-genome sequencing. We also identify future areas of likely growth in the field, including pharmacogenomics and genetic screening for individuals considering or engaged in activities that pose elevated risk of brain injury (e.g., football players, military personnel). APOE gene testing for risk of Alzheimer's disease is used throughout as an instructive case example, drawing upon the authors' experience as investigators in a series of multisite randomized clinical trials that have examined the impact of disclosing APOE genotype status to interested individuals (e.g., first-degree relatives of AD patients, persons with mild cognitive impairment).
随着神经退行性疾病遗传学的深入了解，对高危个体进行遗传易感性测试的机会将会增加。这种测试引发了与测试准入、知情同意、风险评估和沟通、结果回报以及防止遗传歧视的政策相关的重要伦理和实践问题。直接面向消费者的各种神经退行性疾病（包括阿尔茨海默病（AD）、帕金森病和某些朊病毒病）遗传易感性测试的出现意味着，不仅在传统的研究和临床环境中，而且在更广泛的社会中，都必须面对伦理和实践挑战。这篇综述讨论了与研究、临床和消费者环境中遗传易感性测试的开发和实施相关的几个主题；这些主题包括测试的适当指征、不同的测试结果披露方法的含义、风险信息的临床与个人效用、对测试结果的心理和行为反应、未成年人的测试、遗传歧视以及全基因组测序带来的伦理困境。我们还确定了该领域未来可能的增长领域，包括药物遗传学和考虑或从事增加脑损伤风险的活动（例如足球运动员、军人）的个体的遗传筛查。APOE 基因测试用于评估患阿尔茨海默病的风险，作为一个有益的案例示例，借鉴了作者作为一系列多地点随机临床试验的研究者的经验，这些试验研究了向感兴趣的个体（例如 AD 患者的一级亲属、轻度认知障碍患者）披露 APOE 基因型状态的影响。
