Association Between Family History and Early-Onset Atrial Fibrillation Across Racial and Ethnic Groups
Authors: Zain Alzahrani, Aylin Ornelas-Loredo, Sara D. Darbar, Abdullah Farooqui, Denise Mol, Brandon Chalazan, N. Elizabeth Villagrana, Mark McCauley, Sorin Lazar, Erik Wissner, Adarsh Bhan, Sreenivas Konda, Dawood Darbar
Journal: JAMA Network Open (2018)

<h3>Importance</h3> There is a genetic predisposition to early-onset atrial fibrillation (EOAF) in European American individuals. However, the role of family history in the pathogenesis of EOAF in racial and ethnic minorities remains unclear. <h3>Objective</h3> To determine whether probands with EOAF across racial and ethnic groups have a higher rate of AF in first-degree family members than racially and ethnically matched control patients with non–early-onset AF (non-EOAF). <h3>Design, Setting, and Participants</h3> In this cohort study, patients prospectively enrolled in a clinical and genetic biorepository were administered baseline questionnaires that included questions about family history of AF. Early-onset AF was defined as AF occurring in probands aged 60 years or younger in the absence of structural heart disease. All other forms were categorized as non-EOAF. Recruitment took place from July 2015 to December 2017. Analysis was performed in January 2018. <h3>Main Outcomes and Measures</h3> Primary analysis of reported family history of AF in first-degree relatives with sensitivity analysis restricted to those in whom a family history was confirmed by medical record review and electrocardiogram. <h3>Results</h3> Of 664 patients enrolled (mean [SD] age, 62 [12] years; 407 [61%] male), 267 (40%) were European American; 258 (39%), African American; and 139 (21%), Hispanic/Latino. There was a family history of AF in 36 probands with EOAF (49%) compared with 128 patients with non-EOAF (22%) (difference, 27%; 95% CI, 14%-40%;<i>P</i> &lt; .001). On multivariable analysis, the adjusted odds of a proband with EOAF who was of African descent (odds ratio [OR], 2.69; 95% CI, 1.06-6.91;<i>P</i> &lt; .001) or Hispanic descent (OR, 9.25; 95% CI, 2.37-36.23;<i>P</i> = .002) having a first-degree relative with AF were greater than those of European descent (OR, 2.51; 95% CI, 1.29-4.87;<i>P</i> = .006). Overall, probands with EOAF were more likely to have a first-degree relative with AF compared with patients with non-EOAF (adjusted OR, 3.02; 95% CI, 1.82-4.95;<i>P</i> &lt; .001) across the 3 racial and ethnic groups. Atrial fibrillation in a first-degree family member was confirmed in 32% of probands with EOAF vs 11% of those with non-EOAF (difference, 21%; 95% CI, 11%-33%; P &lt; .001). Furthermore, African American (28% vs 5%; difference, 23%; 95% CI, 4%-43%;<i>P</i> = .001), European American (35% vs 20%; difference, 15%; 95% CI, 1%-30%;<i>P</i> = .03), and Hispanic/Latino (30% vs 5%; difference, 25%; 95% CI, 4%-54%;<i>P</i> = .02) probands with EOAF were more likely to have a first-degree relative with confirmed AF vs racially and ethnically matched control patients with non-EOAF. The positive and negative predictive values for a family history of confirmed AF were both 89%. <h3>Conclusions and Relevance</h3> Probands of African or Hispanic/Latino descent with EOAF were more likely to have a first-degree relative with AF when compared with European American individuals. These findings support genetic predisposition to EOAF across all 3 races.