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Here, we characterize a high impact AF-susceptibility allele, <jats:italic>KCNQ1<\/jats:italic> R231H, and describe its transcontinental geographic distribution and history. Induced pluripotent stem cell-derived cardiomyocytes procured from risk allele carriers exhibit abbreviated action potential duration, consistent with a gain-of-function effect. Using identity-by-descent (IBD) networks, we estimate the broad- and fine-scale population ancestry of risk allele carriers and their relatives. Analysis of ancestral migration routes reveals ancestors who inhabited Denmark in the 1700s, migrated to the Northeastern United States in the early 1800s, and traveled across the Midwest to arrive in Utah in the late 1800s. IBD\/coalescent-based allele dating analysis reveals a relatively recent origin of the AF risk allele (~5000 years). Thus, our approach broadens the scope of study for disease susceptibility alleles to the context of human migration and ancestral origins.<\/jats:p>","DOI":"10.1038\/s41467-021-26741-7","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T11:04:19Z","timestamp":1636369459000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The history and geographic distribution of a KCNQ1 atrial fibrillation risk 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