Population-Level Prevalence of Rare Variants Associated With Atrial Fibrillation and its Impact on Patient Outcomes

Kandola, Manjinder Singh; Kulm, Scott; Kim, Luke K.; Markowitz, Steven M.; Liu, Christopher F.; Thomas, George J.; Ip, James E.; Lerman, Bruce B.; Elemento, Olivier; Cheung, Jim W.

doi:10.1016/j.jacep.2022.11.022

Cited by 5 publications

(2 citation statements)

References 35 publications

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“…In total, 7% of our cohort were carriers of at least one actionable P/LP rare variant (N = 91 variants) identified as being associated with arrhythmias, and 4.4% of the actionable variant carriers had AF, emphasizing the potential clinical significance and prevalence of such variants within this specific population cohort. Studies including an analysis of the UK Biobank have reported 4.2% of the population with AF were P/LP carriers [22]. Rare actionable variants were examined within the Middle Eastern population, comparing their prevalence against the gnomAD dataset.…”

Section: Discussionmentioning

confidence: 99%

Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals

Qafoud,

Elshrif,

Kunji

et al. 2024

JCM

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Background: The current study explores the genetic underpinnings of cardiac arrhythmia phenotypes within Middle Eastern populations, which are under-represented in genomic medicine research. Methods: Whole-genome sequencing data from 14,259 individuals from the Qatar Biobank were used and contained 47.8% of Arab ancestry, 18.4% of South Asian ancestry, and 4.6% of African ancestry. The frequency of rare functional variants within a set of 410 candidate genes for cardiac arrhythmias was assessed. Polygenic risk score (PRS) performance for atrial fibrillation (AF) prediction was evaluated. Results: This study identified 1196 rare functional variants, including 162 previously linked to arrhythmia phenotypes, with varying frequencies across Arab, South Asian, and African ancestries. Of these, 137 variants met the pathogenic or likely pathogenic (P/LP) criteria according to ACMG guidelines. Of these, 91 were in ACMG actionable genes and were present in 1030 individuals (~7%). Ten P/LP variants showed significant associations with atrial fibrillation p < 2.4 × 10−10. Five out of ten existing PRSs were significantly associated with AF (e.g., PGS000727, p = 0.03, OR = 1.43 [1.03, 1.97]). Conclusions: Our study is the largest to study the genetic predisposition to arrhythmia phenotypes in the Middle East using whole-genome sequence data. It underscores the importance of including diverse populations in genomic investigations to elucidate the genetic landscape of cardiac arrhythmias and mitigate health disparities in genomic medicine.

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Section: Discussionmentioning

confidence: 99%

Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals

Qafoud,

Elshrif,

Kunji

et al. 2024

JCM

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“…However, few large-scale WES of arrhythmias in the general population have been published. 3 We have used 2 published UK Biobank portals ( https://azphewas.com/ and https://app.genebass.org/ ) to access gene collapsing analysis of rare variations for different types of cardiac arrhythmias. 4 , 5 Identified genes were further analyzed using bioinformatic sources.…”

Section: Introductionmentioning

confidence: 99%

Rare-variant collapsing and bioinformatic analyses for different types of cardiac arrhythmias in the UK Biobank reveal novel susceptibility loci and candidate amyloid-forming proteins

Zöller,

Manderstedt,

Lind-Halldén

et al. 2024

Cardiovascular Digital Health Journal

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Atrial cardiomyopathy in endurance athletes

Spencer,

D’Ambrosio,

Ohanian

et al. 2024

npj Cardiovasc Health

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Atrial cardiomyopathy is characterized by electrical and structural remodeling of the atria, which can predispose to arrhythmias and thromboembolic stroke. Changes in atrial size and function are frequently observed in athletes engaged in endurance sports, a phenomenon known as “athlete’s heart.” Common left atrial observations in athletes may include larger left atrial volumes but lower left atrioventricular volume ratios, mildly reduced left atrial strain, possible mild left atrial fibrosis, longer P-wave duration, and greater atrial ectopic activity. However, it remains unclear whether these changes represent physiological adaptations to endurance exercise or disease-promoting pathology. While the athlete’s heart is considered a benign physiological phenomenon, endurance athletes have an established risk of atrial fibrillation. Therefore, atrial cardiomyopathy represents a significant consideration in disease prognostication and the development of management strategies for athletes. This review examines current literature with respect to the clinical features, causes, and consequences of atrial cardiomyopathy in athletes.

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Population-Level Prevalence of Rare Variants Associated With Atrial Fibrillation and its Impact on Patient Outcomes

Cited by 5 publications

References 35 publications

Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals

Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals

Rare-variant collapsing and bioinformatic analyses for different types of cardiac arrhythmias in the UK Biobank reveal novel susceptibility loci and candidate amyloid-forming proteins

Atrial cardiomyopathy in endurance athletes

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