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.

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