Journal Article

Whole-genome sequencing as an investigational device for return of hereditary disease risk and pharmacogenomic results as part of the All of Us Research Program

Musick, Anjene, Rehm, Heidi L., Lockwood, Christina M., Venner, Eric, Gibbs, Richard A., Topper, Scott E., Metcalf, Ginger A., Gabriel, Stacey, Nickerson, Deborah, Muzny, Donna, Neben, Cynthia L., Lennon, Niall J., Smith, Joshua D., Empey, Phillip E., Walker, Kimberly, Kachulis, Chris, Doheny, Kimberly, Mian, Sana, Zhou, Alicia Y., Ozenberger, Bradley, Harrison, Steven

2022

Overview

Background The All of Us Research Program (AoURP, “the program”) is an initiative, sponsored by the National Institutes of Health (NIH), that aims to enroll one million people (or more) across the USA. Through repeated engagement of participants, a research resource is being created to enable a variety of future observational and interventional studies. The program has also committed to genomic data generation and returning important health-related information to participants. Methods Whole-genome sequencing (WGS), variant calling processes, data interpretation, and return-of-results procedures had to be created and receive an Investigational Device Exemption (IDE) from the United States Food and Drug Administration (FDA). The performance of the entire workflow was assessed through the largest known cross-center, WGS-based, validation activity that was refined iteratively through interactions with the FDA over many months. Results The accuracy and precision of the WGS process as a device for the return of certain health-related genomic results was determined to be sufficient, and an IDE was granted. Conclusions We present here both the process of navigating the IDE application process with the FDA and the results of the validation study as a guide to future projects which may need to follow a similar path. Changes to the program in the future will be covered in supplementary submissions to the IDE and will support additional variant classes, sample types, and any expansion to the reportable regions.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Accuracy / Automation / Biobanks / Bioinformatics / Biomedical and Life Sciences / Biomedicine / Cancer Research / Diseases / DNA sequencing / Ethylenediaminetetraacetic acid / FDA approval / Genetic aspects / Genetic disorders / Genetics / Genomes / Genomics / Hereditary diseases / Human Genetics / Humans / Medical colleges / Medicine / Medicine/Public Health / Metabolomics / Nucleotide sequencing / Pharmacogenetics / Pharmacogenomics / Population Health / Risk factors / Systems Biology / United States / Whole genome sequencing / Whole Genome Sequencing - methods