Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging

The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), is an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences. The journal is global in scope and submission is open to all researchers worldwide.

RESEARCH ARTICLE | January 24, 2020 | https://doi.org/10.1073/pnas.1909378117

Significance

To understand the value and clinical impact of surveying genome-wide disease-causing genes and variants, we used a prospective cohort study design that enrolled volunteers who agreed to have their whole genome sequenced and to participate in deep phenotyping using clinical laboratory tests, metabolomics technologies, and advanced noninvasive imaging. The genomic results are integrated with the phenotype results. Approximately 1 in 6 adult individuals (17.3%) had genetic findings and, when integrated with deep phenotyping data, including family/medical histories with genetic findings, 1 in 9 (11.5%) had genotype and phenotype associations. Genomics and metabolomics association analysis revealed 5.1% of heterozygotes with phenotype manifestations affecting serum metabolite levels. We report observations from our study in which health outcomes and benefits were not measured.