Precision Medicine Screening Using Whole Genome Sequencing and Advanced Imaging To Identify Disease Risk in Adults
Authors: Perkins Bradley A , Thomas Caskey C. , Brar Pamila , Dec Eric , Karow David , Kahn Andrew , Hou Claire , Shah Naisha , Boeldt Debbie , Coughlin Erin , Hands Gabby , Lavrenko Victor , Yu James , Procko Andrea , Appis Julia , Dale Anders , Guo Lining , Jönsson Thomas J. , Wittmann Bryan M. , Bartha Istvan , Ramakrishnan Smriti , Bernal Axel , Brewer James , Brewerton Suzanne , Biggs William H , Turpaz Yaron , Telenti Amalio , Venter J Craig 
Published: May 2017

BACKGROUND

Progress in science and technology have created the capabilities and alternatives to symptom-driven medical care. Reducing premature mortality associated with age-related chronic diseases, such as cancer and cardiovascular disease, is an urgent priority we address using advanced screening detection.

METHODS

We enrolled active adults for early detection of risk for age-related chronic disease associated with premature mortality. Whole genome sequencing together with: global metabolomics, 3D/4D imaging using non-contrast whole body magnetic resonance imaging and echocardiography, and 2-week cardiac monitoring were employed to detect age-related chronic diseases and risk for diseases.

RESULTS

We detected previously unrecognized age-related chronic diseases requiring prompt (<30 days) medical attention in 17 (8%, 1:12) of 209 study participants, including 4 participants with early stage neoplasms (2%, 1:50). Likely mechanistic genomic findings correlating with clinical data were identified in 52 participants (25%. 1:4). More than three-quarters of participants (n=164, 78%, 3:4) had evidence of age-related chronic diseases or associated risk factors.

CONCLUSIONS

Precision medicine screening using genomics with other advanced clinical data among active adults identified unsuspected disease risks for age-related chronic diseases associated with premature mortality. This technology-driven phenotype screening approach has the potential to extend healthy life among active adults through improved early detection and prevention of age-related chronic diseases. Our success provides a scalable strategy to move medical practice and discovery toward risk detection and disease modification thus achieving healthier extension of life.

SIGNIFICANCE STATEMENT

Advances in science and technology have enabled scientists to analyze the human genome cost-effectively and to combine genome sequencing with noninvasive imaging technologies for alternatives to symptom-driven medical care. Using whole genome sequencing and noninvasive 3D/4D imaging technologies we screened 209 adults to detect age-related chronic diseases, such as cancer and cardiovascular disease. We found unrecognized age-related chronic diseases requiring prompt (<30 days) medical attention in 1:12 study participants, likely genomic findings correlating with clinical data in 1:4 participants, and evidence of age-related chronic diseases or associated risk factors in more than 3 of 4 participants. These results demonstrate that genome sequencing with clinical imaging data can be used for screening and early detection of diseases associated with premature mortality.