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

Shannon Hateley, Angelica Lopez-Izquierdo, Chuanchau J. Jou, Scott Cho, Joshua G. Schraiber, Shiya Song, Colin T. Maguire, Natalia Torres, Michael Riedel, Neil E. Bowles, Cammon B. Arrington, Brett J. Kennedy, Susan P. Etheridge, Shuping Lai, Chase Pribble, Lindsay Meyers, Derek Lundahl, Jake Byrnes, Julie M. Granka, Christopher A. Kauffman, Gordon Lemmon, Steven Boyden, W. Scott Watkins, Mary Anne Karren, Stacey Knight, J. Brent Muhlestein, John F. Carlquist, Jeffrey L. Anderson, Kenneth G. Chahine, Khushi U. Shah, Catherine A. Ball, Ivor J. Benjamin, Mark Yandell and Martin Tristani-Firouzi ()
Additional contact information
Shannon Hateley: AncestryDNA
Angelica Lopez-Izquierdo: University of Utah School of Medicine
Chuanchau J. Jou: University of Utah School of Medicine
Scott Cho: University of Utah School of Medicine
Joshua G. Schraiber: AncestryDNA
Shiya Song: AncestryDNA
Colin T. Maguire: University of Utah School of Medicine
Natalia Torres: University of Utah School of Medicine
Michael Riedel: Medical College of Wisconsin
Neil E. Bowles: University of Utah School of Medicine
Cammon B. Arrington: University of Utah School of Medicine
Brett J. Kennedy: University of Utah
Susan P. Etheridge: University of Utah School of Medicine
Shuping Lai: Medical College of Wisconsin
Chase Pribble: University of Utah School of Medicine
Lindsay Meyers: University of Utah School of Medicine
Derek Lundahl: University of Utah School of Medicine
Jake Byrnes: AncestryDNA
Julie M. Granka: AncestryDNA
Christopher A. Kauffman: University of Utah School of Medicine
Gordon Lemmon: University of Utah
Steven Boyden: University of Utah
W. Scott Watkins: University of Utah
Mary Anne Karren: University of Utah
Stacey Knight: The Intermountain Medical Center
J. Brent Muhlestein: The Intermountain Medical Center
John F. Carlquist: The Intermountain Medical Center
Jeffrey L. Anderson: The Intermountain Medical Center
Kenneth G. Chahine: AncestryDNA
Khushi U. Shah: University of Utah School of Medicine
Catherine A. Ball: AncestryDNA
Ivor J. Benjamin: Medical College of Wisconsin
Mark Yandell: University of Utah
Martin Tristani-Firouzi: University of Utah School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26741-7

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DOI: 10.1038/s41467-021-26741-7

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