Precision medicine screening using whole-genome sequencing and advanced imaging to identify disease risk in adults

PNAS – Proceedings of the National Academy of Sciences of the United States
of America

http://www.pnas.org/content/early/
[Accessed 24 March 2018]

Precision medicine screening using whole-genome sequencing and advanced imaging to identify disease risk in adults
Bradley A. Perkins, C. Thomas Caskey, Pamila Brar, Eric Dec, David S. Karow, Andrew M. Kahn, Ying-Chen Claire Hou, Naisha Shah, Debbie Boeldt, Erin Coughlin, Gabby Hands, Victor Lavrenko, James Yu, Andrea Procko, Julia Appis, Anders M. Dale, Lining Guo, Thomas J. Jönsson, Bryan M. Wittmann, Istvan Bartha, Smriti Ramakrishnan, Axel Bernal, James B. Brewer, Suzanne Brewerton, William H. Biggs, Yaron Turpaz and J. Craig Venter
PNAS March 19, 2018. 201706096; published ahead of print March 19, 2018. https://doi.org/10.1073/pnas.1706096114
Significance
Advances in technology are enabling evaluation for prevention and early detection of age-related chronic diseases associated with premature mortality, such as cancer and cardiovascular diseases. These diseases kill about one-third of men and one-quarter of women between the ages of 50 and 74 years old in the United States. We used whole-genome sequencing, advanced imaging, and other clinical testing to screen 209 active, symptom-free adults. We identified a broad set of complementary age-related chronic disease risks associated with premature mortality.
Abstract
Reducing premature mortality associated with age-related chronic diseases, such as cancer and cardiovascular disease, is an urgent priority. We report early results using genomics in combination with advanced imaging and other clinical testing to proactively screen for age-related chronic disease risk among adults. We enrolled active, symptom-free adults in a study of screening for age-related chronic diseases associated with premature mortality. In addition to personal and family medical history and other clinical testing, we obtained whole-genome sequencing (WGS), noncontrast whole-body MRI, dual-energy X-ray absorptiometry (DXA), global metabolomics, a new blood test for prediabetes (Quantose IR), echocardiography (ECHO), ECG, and cardiac rhythm monitoring to identify age-related chronic disease risks. Precision medicine screening using WGS and advanced imaging along with other testing among active, symptom-free adults identified a broad set of complementary age-related chronic disease risks associated with premature mortality and strengthened WGS variant interpretation. This and other similarly designed screening approaches anchored by WGS and advanced imaging may have the potential to extend healthy life among active adults through improved prevention and early detection of age-related chronic diseases (and their risk factors) associated with premature mortality.