Title | Population-Level Prevalence of Rare Variants Associated With Atrial Fibrillation and its Impact on Patient Outcomes. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Kandola MS, Kulm S, Kim LK, Markowitz SM, Liu CF, Thomas G, Ip JE, Lerman BB, Elemento O, Cheung JW |
Journal | JACC Clin Electrophysiol |
Date Published | 2023 Jan 11 |
ISSN | 2405-5018 |
Abstract | BACKGROUND: Whole exome sequencing may identify rare pathogenic/likely pathogenic variants (LPVs) that are linked to atrial fibrillation (AF). The impact of LPVs associated with AF on a population level on outcomes is unclear. OBJECTIVES: This study sought to examine the association of LPVs with AF and their impact on clinical outcomes using the UK Biobank, a national repository of participants with available whole exome sequencing data. METHODS: A total of 200,631 individuals in the UK Biobank were studied. Incident and prevalent AF, comorbidities, and outcomes were identified using self-reported assessments and hospital stay operative, and death registry records. LPVs were determined using arrhythmia and cardiomyopathy gene panels with LOFTEE and ClinVar to predict variants of functional significance. RESULTS: Compared with control subjects, there was a modestly increased prevalence of LPVs among 9,585 patients with AF (2.0% vs 1.7%, respectively; P = 0.01). Among those with prevalent AF at <45 years of age, 4.2% were LPV carriers. LPVs in TTN and PKP2 were associated with AF with adjusted odds ratios of 2.69 (95% CI: 1.57-4.61) and 2.69 (95% CI: 1.54-4.68), respectively. There was no significant difference in combined ischemic stroke, heart failure hospitalization, and mortality among patients who have AF with and without LPVs (25.1% vs 23.8%; P = 0.49). Among participants with AF and available cardiac magnetic resonance imaging data, LPV carriers had lower left ventricular ejection fractions than non-LPV carriers (42% vs 52%; P = 0.027). CONCLUSIONS: Patients with AF had a modestly increased prevalence of LPVs. Among reference arrhythmia and cardiomyopathy genes, the contribution of rare variants to AF risk at a population level is modest and its impact on outcomes appears to be limited, despite an association of LPVs with reduced left ventricular ejection fraction among patients with AF. |
DOI | 10.1016/j.jacep.2022.11.022 |
Alternate Journal | JACC Clin Electrophysiol |
PubMed ID | 36669898 |