Whole Genome Sequencing in support of Wellness and Health Maintenance.

Patel CJ, Sivadas A, Tabassum R, Preeprem T, Zhao J, Arafat D, Chen R, Morgan AA, Martin GS, Brigham KL, Butte AJ, Gibson G.

Abstract

BACKGROUND:

Whole genome sequencing is poised to revolutionize personalized medicine, providing the capacity to classify individuals into risk categories for a wide range of diseases. Here we begin to explore how whole genome sequencing (WGS) might be incorporated alongside traditional clinical evaluation as a part of preventive medicine. The present study illustrates novel approaches for integrating genotypic and clinical information for assessment of generalized health risks and to assist individuals in the promotion of wellness and maintenance of good health.

METHODS:

Whole genome sequences and longitudinal clinical profiles are described for eight middle-aged Caucasian participants (four men and four women) from the Center for Health Discovery and Well Being (CHDWB) at Emory University in Atlanta. We report multivariate genotypic risk assessments derived from common variants reported by genome-wide association studies (GWAS), single rare homozygous deleterious variants, and clinical measures in the domains of immune, metabolic, cardiovascular, musculoskeletal and mental health.

RESULTS:

Polygenic risk is assessed for each participant for over 100 diseases and reported relative to baseline population prevalence. Two approaches for combining clinical and genetic profiles for the purposes of health assessment are then discussed. First we propose conditioning individual disease risk assessments on observed clinical status for type 2 diabetes, coronary artery disease, hypertriglyceridemia and hypertension, and obesity. An excess of concordance between genetic prediction and observed sub-clinical disease is observed. Subsequently, we show how more holistic combination of genetic, clinical and family history data can be achieved by visualizing risk in eight sub-classes of disease. Having identified where their profiles are broadly concordant or discordant, an individual can focus on individual clinical results or genotypes as they develop personalized health action plans in consultation with a health partner.