PROJECT NARRATIVE Though any single rare disease is by definition uncommon, together these diseases affect nearly 30 million individuals in the United States, two-thirds of whom are children, and contribute significantly to morbidity, mortality, and healthcare costs. Exome and whole genome sequencing have the potential to provide a diagnosis to an estimated 25 to 50 percent of those patients struggling with undiagnosed rare diseases, but the downstream costs and benefits of this testing beyond diagnosis remain largely unknown.

PROJECT NARRATIVE/ RELEVANCE OF PROJECT TO RESEARCH AND PUBLIC HEALTH Widespread utilization of genomic sequencing in medicine creates an urgent need to educate providers and patients. Currently, providers frequently misinterpret genomic information and patients often don't understand their own test results. In order to address this critical need, we propose to design and test multiple e-Health communication tools that will help providers and patients to better understand genomic data, lead to higher quality patient care, and facilitate genomic information sharing within families.

PROJECT NARRATIVE: Recent recommendations to return children?s results for adult-onset conditions to parents anytime whole exome or genome sequencing is performed, as well as growing expectations to return research results to participants on a large-scale basis, mean adolescents will increasingly be engaged in assenting (<age 18) and consenting (>age 18) to return of genomic research results. There is an urgent need to understand adolescents?

PROJECT NARRATIVE The central goal of the proposed research is to determine the cost-effectiveness of integrating whole genome sequencing into the care of healthy adults. We will assess the health impact and cumulative healthcare costs of participants of a randomized clinical trial of whole genome sequencing five years after they received results, and we will extend these analyses over patients' lifetimes using decision analytic models. Findings will inform development of clinical guidelines and reimbursement strategies to accelerate the integration of sequencing into medical care.

Prenatal screening and testing technologies using genetic methods are rapidly expanding, offering increasing amounts of genetic information about the fetus. However, research shows that women from underserved populations are less likely to receive or accept prenatal genetic services, leading to discordant birth outcomes. We propose to explore the barriers to access and acceptance of prenatal genetic care among women from underserved populations.

Project Narrative. Advances in psychiatric, neurologic and behavioral (PNB) genetics have brought the prospect of predictive and diagnostic genomic testing for many PNB conditions closer to clinical application. The potential for such findings to profoundly affect core elements of personhood?including identity, perceived responsibilities, and life trajectories?makes it essential to understand the impact of such information on individuals and families.