Evidence for a Heritable Contribution to Atrial Fibrillation Associated 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: 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.