Returning Individual Genetic Results to Participants in Cohort Studies

总结/摘要 方法学的进步现在允许使用全基因组关联研究（GWAS） 发现新的基因型-表型关联。GWAS提供了一个强大的工具， 基因对常见和罕见疾病的贡献。同时，GWAS提高了 深刻而富有挑战性的伦理问题。最紧迫的问题来自于 GWAS将揭示具有临床潜力的遗传信息的可能性 对个人参与者有意义。因此，调查人员将不可避免地面临这样的问题： 是否应该向受试者披露全基因组扫描的个体遗传结果。 评论员和道德小组讨论了基因检测是否 研究结果应返还给研究参与者。大多数政策制定者主张谨慎 办法：披露应限于符合严格标准的一小部分成果 与风险程度、表型严重程度和预防、治疗和预防药物的可用性相关。 或生殖干预。另一方面，关于研究参与者观点的数据有限 另一方面，表明强烈倾向于披露测试结果。由于这些数据 是基于对单一问题的二分回答，他们不解决是否 与会者的意见对专家小组确定的对决策至关重要的因素很敏感 关于返回结果。没有这些信息，就不可能知道差距 参与者的观点和政策指导之间的关系正如数据所显示的那样深刻。 目前的建议旨在通过对1800名成员进行因子调查来弥补这一差距， 杰克逊和弗雷泽心脏研究，两个有影响力的心血管队列研究， 进行GWAS。具体而言，拟议的研究将评估标准是否强调 政策制定者对研究参与者对这一信息的需求的预测。研究 还将评估态度特征之间的关系（例如，看法和 关于遗传学的知识）和社会人口特征（例如，年龄、教育程度）和 参与者对结果回报的渴望。调查结果将有助于评估 专家和研究参与者的观点一致， 这个令人烦恼的话题。这些数据将有助于形成有关返回的做法和政策。 来自基因组研究的个别结果。

SUMMARY/ABSTRACT Methodological advances now permit the use of genome-wide association studies (GWAS) to discover novel genotype-phenotype associations. GWAS offer a powerful tool for identifying genetic contributions to both common and rare diseases. At the same time, GWAS raise profound and challenging ethical questions. The most pressing questions derive from the likelihood that GWAS will uncover genetic information with the potential to be clinically meaningful to individual participants. As a result, investigators will inevitably face the question of whether individual genetic results from genome-wide scans should be disclosed to subjects. Commentators and ethics panels have addressed the question of whether genetic test results should be returned to research participants. Most policymakers advocate a cautious approach: disclosure should be limited to a narrow subset of results that meet stringent criteria related to magnitude of risk, severity of phenotype, and availability of prophylactic, therapeutic or reproductive interventions. Limited data regarding research participants' views, on the other hand, suggest a strong preference for disclosure of test results. However, because these data are based upon dichotomous responses to single questions, they do not address whether participants' views are sensitive to the factors identified by expert panels as salient to decisions about return of results. Without such information, it is impossible to know whether the gap between participants' views and policy guidance is as profound as the data suggest. The present proposal aims to bridge this gap through a factorial survey of 1800 members of the Jackson and Framingham Heart Studies, two influential cardiovascular cohort studies that conduct GWAS. Specifically, the proposed study will evaluate whether the criteria highlighted by policymakers are predictive of research participants' desires for this information. The study will also evaluate the relationships between attitudinal characteristics (e.g., views on and knowledge about genetics) and sociodemographic characteristics (e.g., age, education) and participants' desires for return of results. The findings will permit assessment of the extent to which there is concordance between the views of experts and those of research participants on this vexing topic. These data will help shape practice and policy regarding the return of individual results from genomic research.