Common and rare variants associated with cardiometabolic traits across 98,622 whole-genome sequences in the All of Us research program.

All of Us is a biorepository aiming to advance biomedical research by providing various types of data in diverse human populations. Here we present a demonstration project validating the program's genomic data in 98,622 participants. We sought to replicate known genetic associations for three diseases (atrial fibrillation [AF], coronary artery disease, type 2 diabetes [T2D]) and two quantitative traits (height and low-density lipoprotein [LDL]) by conducting common and rare variant analyses. We identified one known risk locus for AF, five loci for T2D, 143 loci for height, and nine loci for LDL. In gene-based burden tests for rare loss-of-function variants, we replicated associations between TTN and AF, GIGYF1 and T2D, ADAMTS17, ACAN, NPR2 and height, APOB, LDLR, PCSK9 and LDL. Our results are consistent with previous literature, indicating that the All of Us program is a reliable resource for advancing the understanding of complex diseases in diverse human populations.

The All of Us Data and Research Center: Creating a Secure, Scalable, and Sustainable Ecosystem for Biomedical Research.

The All of Us Research Program's Data and Research Center (DRC) was established to help acquire, curate, and provide access to one of the world's largest and most diverse datasets for precision medicine research. Already, over 500,000 participants are enrolled in All of Us, 80% of whom are underrepresented in biomedical research, and data are being analyzed by a community of over 2,300 researchers. The DRC created this thriving data ecosystem by collaborating with engaged participants, innovative program partners, and empowered researchers. In this review, we first describe how the DRC is organized to meet the needs of this broad group of stakeholders. We then outline guiding principles, common challenges, and innovative approaches used to build the All of Us data ecosystem. Finally, we share lessons learned to help others navigate important decisions and trade-offs in building a modern biomedical data platform.

Epidemiology of atrial fibrillation in the All of Us Research Program.

BACKGROUND: The prevalence, incidence and risk factors of atrial fibrillation (AF) in a large, geographically and ethnically diverse cohort in the United States have not been fully described. METHODS: We analyzed data from 173,099 participants of the All of Us Research Program recruited in the period 2017-2019, with 92,318 of them having electronic health records (EHR) data available, and 35,483 having completed a medical history survey. Presence of AF at baseline was identified from self-report and EHR records. Incident AF was obtained from EHR. Demographic, anthropometric and clinical risk factors were obtained from questionnaires, baseline physical measurements and EHR. RESULTS: At enrollment, mean age was 52 years old (range 18-89). Females and males accounted for 61% and 39% respectively. Non-Hispanic Whites accounted for 67% of participants, with non-Hispanic Blacks, non-Hispanic Asians and Hispanics accounting for 26%, 4% and 3% of participants, respectively. Among 92,318 participants with available EHR data, 3,885 (4.2%) had AF at the time of study enrollment, while the corresponding figure among 35,483 with medical history data was 2,084 (5.9%). During a median follow-up of 16 months, 354 new cases of AF were identified among 88,433 eligible participants. Individuals who were older, male, non-Hispanic white, had higher body mass index, or a prior history of heart failure or coronary heart disease had higher prevalence and incidence of AF. CONCLUSION: The epidemiology of AF in the All of Us Research Program is similar to that reported in smaller studies with careful phenotyping, highlighting the value of this new resource for the study of AF and, potentially, other cardiovascular diseases.