The history and geographic distribution of a KCNQ1 atrial fibrillation risk allele.

Autor: Hateley S; AncestryDNA, San Francisco, CA, USA., Lopez-Izquierdo A; Nora Eccles Harrison CVRTI, University of Utah School of Medicine, Salt Lake City, UT, USA., Jou CJ; Nora Eccles Harrison CVRTI, University of Utah School of Medicine, Salt Lake City, UT, USA.; Division of Pediatric Cardiology, University of Utah School of Medicine, Salt Lake City, UT, USA., Cho S; Nora Eccles Harrison CVRTI, University of Utah School of Medicine, Salt Lake City, UT, USA., Schraiber JG; AncestryDNA, San Francisco, CA, USA., Song S; AncestryDNA, San Francisco, CA, USA., Maguire CT; Nora Eccles Harrison CVRTI, University of Utah School of Medicine, Salt Lake City, UT, USA., Torres N; Nora Eccles Harrison CVRTI, University of Utah School of Medicine, Salt Lake City, UT, USA., Riedel M; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA., Bowles NE; Division of Pediatric Cardiology, University of Utah School of Medicine, Salt Lake City, UT, USA., Arrington CB; Division of Pediatric Cardiology, University of Utah School of Medicine, Salt Lake City, UT, USA., Kennedy BJ; Department of Human Genetics, University of Utah, Salt Lake City, UT, USA., Etheridge SP; Division of Pediatric Cardiology, University of Utah School of Medicine, Salt Lake City, UT, USA., Lai S; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA., Pribble C; Nora Eccles Harrison CVRTI, University of Utah School of Medicine, Salt Lake City, UT, USA., Meyers L; Division of Pediatric Cardiology, University of Utah School of Medicine, Salt Lake City, UT, USA., Lundahl D; Division of Pediatric Cardiology, University of Utah School of Medicine, Salt Lake City, UT, USA., Byrnes J; AncestryDNA, San Francisco, CA, USA., Granka JM; AncestryDNA, San Francisco, CA, USA., Kauffman CA; Nora Eccles Harrison CVRTI, University of Utah School of Medicine, Salt Lake City, UT, USA., Lemmon G; Department of Human Genetics, University of Utah, Salt Lake City, UT, USA., Boyden S; Department of Human Genetics, University of Utah, Salt Lake City, UT, USA., Scott Watkins W; Department of Human Genetics, University of Utah, Salt Lake City, UT, USA., Karren MA; Department of Human Genetics, University of Utah, Salt Lake City, UT, USA., Knight S; The Intermountain Medical Center, Murray, UT, USA., Brent Muhlestein J; The Intermountain Medical Center, Murray, UT, USA., Carlquist JF; The Intermountain Medical Center, Murray, UT, USA., Anderson JL; The Intermountain Medical Center, Murray, UT, USA., Chahine KG; AncestryDNA, San Francisco, CA, USA., Shah KU; Nora Eccles Harrison CVRTI, University of Utah School of Medicine, Salt Lake City, UT, USA., Ball CA; AncestryDNA, San Francisco, CA, USA., Benjamin IJ; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA., Yandell M; Department of Human Genetics, University of Utah, Salt Lake City, UT, USA., Tristani-Firouzi M; Nora Eccles Harrison CVRTI, University of Utah School of Medicine, Salt Lake City, UT, USA. martin.tristani@utah.edu.; Division of Pediatric Cardiology, University of Utah School of Medicine, Salt Lake City, UT, USA. martin.tristani@utah.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Nov 08; Vol. 12 (1), pp. 6442. Date of Electronic Publication: 2021 Nov 08.
DOI: 10.1038/s41467-021-26741-7
Abstrakt: The genetic architecture of atrial fibrillation (AF) encompasses low impact, common genetic variants and high impact, rare variants. Here, we characterize a high impact AF-susceptibility allele, KCNQ1 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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