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The aim of this study is to examine the association of rurality with electronic health record-derived disease profiles and heart failure risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective observational study of 242\u00a0758 participants enrolled in the All of Us Research Program. Rurality status was estimated using 2010 Rural-Urban Commuting Area codes from participant home 3-digit zip code prefixes, and participants were grouped into rural, mixed, and urban arms. We compared the disease profiles with phenome-wide association studies and the risks of heart failure between arms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The final cohort included 5581 participants in the rural arm, 62\u00a0287 in the mixed arm, and 174\u00a0890 in the urban arm. Compared to the urban setting, 70 phecodes were significantly enriched in the rural arm including obesity (odds ratio [OR], 1.42, 95% confidence interval [CI], 1.34-1.51) and related diagnoses. Cancer screening-, dermatological-, and eye care-related diagnoses were significantly depleted in the rural arm. The rural arm also showed a greater risk of heart failure (adjusted hazard ratio [HR], 1.20, 95% CI, 1.10-1.31).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and Conclusion<\/jats:title>\n                    <jats:p>With the national dataset in All of Us, we found that rural participants had significantly higher risks for obesity-related diseases and heart failure in this study. Depleted phecodes in the rural participants suggested a lack of access to cancer screening, stressing the potential importance of targeted cancer disease management in rural communities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jamiaopen\/ooag086","type":"journal-article","created":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T11:32:19Z","timestamp":1779017539000},"source":"Crossref","is-referenced-by-count":0,"title":["A phenome-wide association study of rurality in the\n                    <i>All of Us<\/i>\n                    Research Program"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2168-8812","authenticated-orcid":false,"given":"Anas H","family":"Awan","sequence":"first","affiliation":[{"name":"Precision Health Informatics Section, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH) , Bethesda, MD, 20892,","place":["United States"]},{"name":"The Cohort Analytics Core (CAC), Center 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