Certain large genome cohort studies attempt to return the individual genomic results to the participants; however, the implementation process and psychosocial impacts remain largely unknown. The Tohoku Medical Megabank Project has conducted large genome cohort studies of general residents. To implement the disclosure of individual genomic results, we extracted the potential challenges and obstacles. Major challenges include the determination of genes/disorders based on the current medical system in Japan, the storage of results, prevention of misunderstanding, and collaboration of medical professionals. To overcome these challenges, we plan to conduct multilayer pilot studies, which deal with different disorders/genes. We finally chose familial hypercholesterolemia (FH) as a target disease for the first pilot study. Of the 665 eligible candidates, 33.5% were interested in the pilot study and provided consent after an educational “genetics workshop” on the basic genetics and medical facts of FH. The genetics professionals disclosed the results to the participants. All positive participants were referred to medical care, and a serial questionnaire revealed no significant psychosocial distress after the disclosure. Return of genomic results to research participants was implemented using a well-prepared protocol. To further elucidate the impact of different disorders, we will perform multilayer pilot studies with different disorders, including actionable pharmacogenomics and hereditary tumor syndromes.

某些大型基因组队列研究试图将个体基因组结果返回给参与者；然而，实施过程和社会心理影响在很大程度上仍然未知。Tohoku Medical Megabank Project 对普通居民进行了大型基因组队列研究。为了实现个体基因组结果的披露，我们提取了潜在的挑战和障碍。主要挑战包括基于日本当前医疗系统的基因/疾病确定、结果的存储、防止误解以及医疗专业人员的协作。为了克服这些挑战，我们计划进行多层次的试点研究，处理不同的疾病/基因。我们最终选择家族性高胆固醇血症 (FH) 作为第一个试点研究的目标疾病。在 665 名符合条件的候选人中，33.5% 对试点研究感兴趣，并在关于 FH 的基本遗传学和医学事实的教育“遗传学研讨会”后表示同意。遗传学专家向参与者披露了结果。所有积极的参与者都被转诊到医疗机构，一系列问卷调查显示在披露后没有明显的社会心理困扰。使用精心准备的协议将基因组结果返回给研究参与者。为了进一步阐明不同疾病的影响，我们将对不同疾病进行多层试点研究，包括可操作的药物基因组学和遗传性肿瘤综合征。遗传学专家向参与者披露了结果。所有积极的参与者都被转诊到医疗机构，一系列问卷调查显示在披露后没有明显的社会心理困扰。使用精心准备的协议将基因组结果返回给研究参与者。为了进一步阐明不同疾病的影响，我们将对不同疾病进行多层试点研究，包括可操作的药物基因组学和遗传性肿瘤综合征。遗传学专家向参与者披露了结果。所有积极的参与者都被转诊到医疗机构，一系列问卷调查显示在披露后没有明显的社会心理困扰。使用精心准备的协议将基因组结果返回给研究参与者。为了进一步阐明不同疾病的影响，我们将对不同疾病进行多层试点研究，包括可操作的药物基因组学和遗传性肿瘤综合征。