Author + information
- Received October 3, 2018
- Revision received January 5, 2019
- Accepted January 7, 2019
- Published online April 15, 2019.
- Brent D. Wilson, MD, PhDa,b,
- Stephen L. Wasmund, PhDa,b,
- Frank B. Sachse, PhDb,c,d,
- Gagandeep Kaur, BSb,
- Nassir F. Marrouche, MDa,b and
- Lisa A. Cannon-Albright, PhDb,e,f,g,∗ ()
- aDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah
- bComprehensive Arrhythmia Research and Management Center, University of Utah Health, Salt Lake City, Utah
- cNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah
- dDepartment of Biomedical Engineering, University of Utah, Salt Lake City, Utah
- eGenetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah
- fHuntsman Cancer Institute, Salt Lake City, Utah
- gGeorge E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah
- ↵∗Address for correspondence:
Dr. Lisa A. Cannon-Albright, Genetic Epidemiology, University of Utah, 391 Chipeta Way, Suite D, Salt Lake City, Utah 84108.
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.
Partial support for Dr. Cannon-Albright and for all datasets within the Utah Population Database was provided by Huntsman Cancer Institute, Huntsman Cancer Foundation, University of Utah, and the Huntsman Cancer Institute's Cancer Center Support grant P30 CA42014 from National Cancer Institute. Dr. Sachse is partially supported by the Nora Eccles Treadwell Foundation. Dr. Marrouche has ownership interest in Marrek, Inc. and Cardiac Designs; has performed contracted research for Biosense Webster, Medtronic, St. Jude, Biotronik, and Boston Scientific; and has received consulting fees from Biotronik and Preventice. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Received October 3, 2018.
- Revision received January 5, 2019.
- Accepted January 7, 2019.
- 2019 American College of Cardiology Foundation
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