In this highly collaborative multi-disciplinary initiative, we propose to explore and compare the impact of using WGS in clinical conditions that model pure forms of each of these approaches. To model General Genomic Medicine, 10 primary care physicians and 100 of their healthy middle-aged patients will be enrolled. To model Disease-Specific Genomic Medicine, 10 cardiologists and 100 of their patients presenting with familial hypertrophic cardiomyopathy (HCM) will be enrolled. We will conduct an exploratory clinical trial randomizing physicians and their patients within each of these models to receive clinically meaningful information derived from WGS versus current standard of care. Project 1 will create standards for variant disclosure, enroll physicians and patients into the protocol and safely monitor the use of genomic information in clinical practice. Project 2 will sequence, analyze and interpret WGS for the physicians to use. And Project 3 will examine preferences and motivations of physicians and patients enrolled, evaluate the flow and utilization of genomic information within the clinical interactions, and assess understanding, behavior, medical consequences and healthcare costs associated with the use of WGS in these models of medical practice. This initiative will significantly accelerate the use of genomics into clinical medicine by creating and safely testing novel ways of integrating information from WGS into physician care of patients.

Public Health Relevance

Physicians will soon use WGS to derive insight into future health risks and inform prevention efforts in healthy patients and to interrogate particular sets o genes known to be associated with disease in patients presenting with a family history and symptoms. The results of this study will accelerate the use of genomics in clinical medicine by creating and testing ways to integrate WGS into physician care of patients.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZHG1-HGR-N (O1))
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Hindorff, Lucia
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Brigham and Women's Hospital
United States
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MacRae, Calum A; Vasan, Ramachandran S (2014) Clinically relevant functional annotation of genotype. Circ Cardiovasc Genet 7:2-3
Hivert, Marie-France; Vassy, Jason L; Meigs, James B (2014) Susceptibility to type 2 diabetes mellitus--from genes to prevention. Nat Rev Endocrinol 10:198-205
Triedman, John K; MacRae, Calum (2014) Searching for a Rosetta Stone: genetic data and clinical patient management. Heart Rhythm 11:1714-5
Sharp, Aaron R; Ridge, Perry G; Bailey, Matthew H et al. (2014) Population substructure in Cache County, Utah: the Cache County study. BMC Bioinformatics 15 Suppl 7:S8
Holm, Ingrid A; Savage, Sarah K; Green, Robert C et al. (2014) Guidelines for return of research results from pediatric genomic studies: deliberations of the Boston Children's Hospital Gene Partnership Informed Cohort Oversight Board. Genet Med 16:547-52
Ziniel, S I; Savage, S K; Huntington, N et al. (2014) Parents' preferences for return of results in pediatric genomic research. Public Health Genomics 17:105-14
Walford, Geoffrey A; Porneala, Bianca C; Dauriz, Marco et al. (2014) Metabolite traits and genetic risk provide complementary information for the prediction of future type 2 diabetes. Diabetes Care 37:2508-14
Vassy, Jason L; Hivert, Marie-France; Porneala, Bianca et al. (2014) Polygenic type 2 diabetes prediction at the limit of common variant detection. Diabetes 63:2172-82
Jarvik, Gail P; Amendola, Laura M; Berg, Jonathan S et al. (2014) Return of genomic results to research participants: the floor, the ceiling, and the choices in between. Am J Hum Genet 94:818-26
Poggesi, Corrado; Ho, Carolyn Y (2014) Muscle dysfunction in hypertrophic cardiomyopathy: what is needed to move to translation? J Muscle Res Cell Motil 35:37-45

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