Genomic data in the All of Us Research Program
Authors:   The All of Us Research Program Genomics Investigators,   Manuscript Writing Group, Bick Alexander G. , Metcalf Ginger A. , Mayo Kelsey R. , Lichtenstein Lee , Rura Shimon , Carroll Robert J. , Musick Anjene , Linder Jodell E. , Jordan I. King , Nagar Shashwat Deepali , Sharma Shivam , Meller Robert ,   All of Us Research Program Genomics Principal Investigators, Basford Melissa , Boerwinkle Eric , Cicek Mine S. , Doheny Kimberly F. , Eichler Evan E. , Gabriel Stacey , Gibbs Richard A. , Glazer David , Harris Paul A. , Jarvik Gail P. , Philippakis Anthony , Rehm Heidi L. , Roden Dan M. , Thibodeau Stephen N. , Topper Scott ,   Biobank, Mayo, Blegen Ashley L. , Wirkus Samantha J. , Wagner Victoria A. , Meyer Jeffrey G. , Cicek Mine S. ,   Genome Center: Baylor-Hopkins Clinical Genome Center, Muzny Donna M. , Venner Eric , Mawhinney Michelle Z. , Griffith Sean M. L. , Hsu Elvin , Ling Hua , Adams Marcia K. , Walker Kimberly , Hu Jianhong , Doddapaneni Harsha , Kovar Christie L. , Murugan Mullai , Dugan Shannon , Khan Ziad , Boerwinkle Eric ,   Genome Center: Broad, Color, and Mass General Brigham Laboratory for Molecular Medicine, Lennon Niall J. , Austin-Tse Christina , Banks Eric , Gatzen Michael , Gupta Namrata , Henricks Emma , Larsson Katie , McDonough Sheli , Harrison Steven M. , Kachulis Christopher , Lebo Matthew S. , Neben Cynthia L. , Steeves Marcie , Zhou Alicia Y. ,   Genome Center: University of Washington, Smith Joshua D. , Frazar Christian D. , Davis Colleen P. , Patterson Karynne E. , Wheeler Marsha M. , McGee Sean , Lockwood Christina M. , Shirts Brian H. , Pritchard Colin C. , Murray Mitzi L. , Vasta Valeria , Leistritz Dru , Richardson Matthew A. , Buchan Jillian G. , Radhakrishnan Aparna , Krumm Niklas , Ehmen Brenna W. ,   Data and Research Center, Schwartz Sophie , Aster M. Morgan T. , Cibulskis Kristian , Haessly Andrea , Asch Rebecca , Cremer Aurora , Degatano Kylee , Shergill Akum , Gauthier Laura D. , Lee Samuel K. , Hatcher Aaron , Grant George B. , Brandt Genevieve R. , Covarrubias Miguel , Banks Eric , Able Ashley , Green Ashley E. , Carroll Robert J. , Zhang Jennifer , Condon Henry R. , Wang Yuanyuan , Dillon Moira K. , Albach C. H. , Baalawi Wail ,   All of Us Research Demonstration Project Teams, Choi Seung Hoan , Wang Xin , Rosenthal Elisabeth A. ,   NIH All of Us Research Program Staff, Ramirez Andrea H. , Lim Sokny , Nambiar Siddhartha , Ozenberger Bradley , Wise Anastasia L. , Lunt Chris , Ginsburg Geoffrey S. , Denny Joshua C. 
Published: February 2024

AbstractComprehensively mapping the genetic basis of human disease across diverse individuals is a long-standing goal for the field of human genetics1–4. The All of Us Research Program is a longitudinal cohort study aiming to enrol a diverse group of at least one million individuals across the USA to accelerate biomedical research and improve human health5,6. Here we describe the programme’s genomics data release of 245,388 clinical-grade genome sequences. This resource is unique in its diversity as 77% of participants are from communities that are historically under-represented in biomedical research and 46% are individuals from under-represented racial and ethnic minorities. All of Us identified more than 1 billion genetic variants, including more than 275 million previously unreported genetic variants, more than 3.9 million of which had coding consequences. Leveraging linkage between genomic data and the longitudinal electronic health record, we evaluated 3,724 genetic variants associated with 117 diseases and found high replication rates across both participants of European ancestry and participants of African ancestry. Summary-level data are publicly available, and individual-level data can be accessed by researchers through the All of Us Researcher Workbench using a unique data passport model with a median time from initial researcher registration to data access of 29 hours. We anticipate that this diverse dataset will advance the promise of genomic medicine for all.