Brent D Wilson1, Stephen L Wasmund1, Frank B Sachse2, Gagandeep Kaur3, Nassir F Marrouche1, Lisa A Cannon-Albright4. 1. Division of Cardiovascular Medicine, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah; Comprehensive Arrhythmia Research and Management Center, University of Utah Health, Salt Lake City, Utah. 2. Comprehensive Arrhythmia Research and Management Center, University of Utah Health, Salt Lake City, Utah; Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah; Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah. 3. Comprehensive Arrhythmia Research and Management Center, University of Utah Health, Salt Lake City, Utah. 4. Comprehensive Arrhythmia Research and Management Center, University of Utah Health, Salt Lake City, Utah; Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah; Huntsman Cancer Institute, Salt Lake City, Utah; George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah. Electronic address: lisa.albright@utah.edu.
Abstract
OBJECTIVES: The aim of this study was to define the population-based familial clustering of atrial fibrillation (AF) that is associated with fibrosis and describe evidence for a heritable predisposition. BACKGROUND: Although a heritable contribution to AF is well-established and the association of fibrosis with AF is well-recognized, no studies have analyzed the genetic contribution to AF co-occurring with fibrosis. METHODS: AF patients with magnetic resonance imaging-confirmed fibrosis were identified in a population-based health sciences center database linked to a Utah genealogy. Familial clustering of AF/fibrosis was defined by analysis of pairwise case relatedness, estimation of relative risk of AF/fibrosis in relatives, and identification of high-risk AF/fibrosis pedigrees. RESULTS: The 694 individuals identified with AF/fibrosis who had at least 3 generations of genealogy data were found to have significantly elevated pairwise relatedness (p < 0.001), even when first- and second-degree relationships were ignored (p < 0.001). Significantly elevated risks for AF/fibrosis among first- (relative risk [RR]: 4.65), second- (RR: 3.14), and third-degree (RR: 2.70) relatives of individuals with AF/fibrosis were observed. We identified 157 extended Utah pedigrees with a significant excess of AF/fibrosis among descendants. CONCLUSIONS: There is a strong heritable contribution to predisposition to AF co-occurring with fibrosis. We suggest that this study provides a unique foundation for a search for predisposition genes, specifically for AF co-occurring with fibrosis.
OBJECTIVES: The aim of this study was to define the population-based familial clustering of atrial fibrillation (AF) that is associated with fibrosis and describe evidence for a heritable predisposition. BACKGROUND: Although a heritable contribution to AF is well-established and the association of fibrosis with AF is well-recognized, no studies have analyzed the genetic contribution to AF co-occurring with fibrosis. METHODS:AFpatients with magnetic resonance imaging-confirmed fibrosis were identified in a population-based health sciences center database linked to a Utah genealogy. Familial clustering of AF/fibrosis was defined by analysis of pairwise case relatedness, estimation of relative risk of AF/fibrosis in relatives, and identification of high-risk AF/fibrosis pedigrees. RESULTS: The 694 individuals identified with AF/fibrosis who had at least 3 generations of genealogy data were found to have significantly elevated pairwise relatedness (p < 0.001), even when first- and second-degree relationships were ignored (p < 0.001). Significantly elevated risks for AF/fibrosis among first- (relative risk [RR]: 4.65), second- (RR: 3.14), and third-degree (RR: 2.70) relatives of individuals with AF/fibrosis were observed. We identified 157 extended Utah pedigrees with a significant excess of AF/fibrosis among descendants. CONCLUSIONS: There is a strong heritable contribution to predisposition to AF co-occurring with fibrosis. We suggest that this study provides a unique foundation for a search for predisposition genes, specifically for AF co-occurring with fibrosis.
Authors: Laura Andreasen; Litten Bertelsen; Jonas Ghouse; Pia R Lundegaard; Gustav Ahlberg; Lena Refsgaard; Torsten B Rasmussen; Hans Eiskjær; Stig Haunsø; Niels Vejlstrup; Jesper H Svendsen; Morten S Olesen Journal: Sci Rep Date: 2020-06-22 Impact factor: 4.379
Authors: 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; Martin Tristani-Firouzi Journal: Nat Commun Date: 2021-11-08 Impact factor: 14.919