ClinSeq - Clinical and Behavioral Aspects

在2013财年，我们通过开展以下正在进行的子研究，大幅推进了ClinSeq（c）临床和行为项目的目标和目的。 偶然发现。 偶然发现的主题已经成为临床和研究议程的一部分，ClinSeq（c）研究在很大程度上促进了这一主题。在前期，我们通过在ClinSeq（c）参与者中鉴定癌症易感性变体来试点偶然发现（约翰斯顿et al，2012）。在此期间，我们通过将其扩展到心肌病和心律失常变体的新项目（Ng et al，In Press）和恶性高热的第二个项目（Gonsalves et al，In Press）来扩展这项工作。我们正在将其扩展到一个更广泛的项目中，以探索已知以常染色体显性模式引起人类疾病的基因中的所有无效变体（新的和已知的），并将其与表型相关联。该项目将延续到下一个报告所述期间。实际上，ClinSeq（c）经验极大地促进了美国医学遗传学学会发布的关于偶然发现的建议（绿色等人，2013）。 调查参与者的态度和知情同意。 由于测序技术是新的，重要的是要了解患者将如何理解和采用这项技术。为此，我们对参与者进行了调查，以了解参与研究的动机（Facio et al，2012 a）和获得结果的意图（Facio et al，2012 b）。我们还调查了他们，以衡量他们的理解的深度，这是相当高的（Kaphingst等人，2013年）。最后，我们撰写了一篇理论论文，提出了一种新的知情同意方法，用于ClinSeq（c）等研究，这些研究为临床研究提供了假设（Facio et al，2013）。在即将到来的一年里，我们对这种测序技术的基线态度进行了广泛的调查。 返回结果。 我们目前正在确定参与者中已知的致病基因变异。对于已知的主要特征，我们正在返回那些被确定的特征，并对参与者进行定性访谈，以评估他们的反应以及他们计划如何使用结果。此外，我们计划进行一项大型对照实验，实验组采用不同的结果返回模式，以比较临床医生直接交互的经典模式与基于网络的结果返回新模式。

In FY2013 we have substantially advanced the goals and objectives for the ClinSeq(c) clinical and behavioral project by performing the following ongoing substudies. Incidental findings. The topic of incidental findings has exploded onto the clinical and research agenda, to no small extent facilitated by the ClinSeq(c) study. In the prior period, we piloted incidental findings by identifying cancer susceptibility variants in ClinSeq(c) participants (Johnston et al, 2012). In this period, we have expanded this effort by extending it into a new project on cardiomyopathy and dysrhythmia variants (Ng et al, In Press) and a second project on malignant hyperthermia (Gonsalves et al, In Press). We are extending this into a broader project to explore all null variants (novel and known) in genes known to cause human disease in an autosomal dominant pattern and correlating this with phenotype. This project will extend into the next reporting period. Indeed, the ClinSeq(c) experience substantially contributed to the recommendations issued by the American College of Medical Genetics on incidental findings (Green et al, 2013). Surveying participant attitudes and informed consent. As sequencing technology is new, it is important to understand how patients will understand and take up this technology. To that end, we have surveyed our participants to understand the motivations for participating in the study (Facio et al, 2012a) and the intentions to receive results (Facio et al 2012b). We have also surveyed them to gauge the depth of their understanding, which was quite high (Kaphingst et al., 2013). Finally, we have written a theoretical paper that proposes a novel approach to informed consent for studies like ClinSeq(c), which generate hypotheses for clinical research (Facio et al, 2013). For the upcoming year, we have developed an extensive survey of baseline attitudes towards this sequencing technology. Return of results. We are currently identifying known pathogenic gene variants in our participants. For the known dominant traits, we are returning those as they are identified and are performing qualitative interviews on the participants to gauge their reactions and how they plan to use the results. In addition, we are planning a large, controlled experiment with experimental arms that vary the mode of return of results to compare the classical model of direct clinician interaction with a new mode of web-based results return.