DECIPHERING THE GENETIC UNDERPINNINGS OF ATRIAL FIBRILLATION IN ARAB PATIENTS THROUGH WHOLE EXOME SEQUENCING

Abstract

Atrial Fibrillation (AF) is a type of cardiac arrhythmia characterized by high-frequency excitation of the atrium. The role of genetic variability in the etiology and pathogenesis of AF is being increasingly recognized. 37 genes were previously implicated in AF susceptibility. Despite significant advancements in unraveling the genetic basis of AF, significant gaps remain in this field, necessitating further research, particularly within Arab populations. The aim of this study is to bridge the gaps in AF genetic research within the Arab population by investigating the genetic underpinnings of AF and identifying rare genetic variants associated with AF in an Arab cohort comprising 30 patients of diverse nationalities recruited from Qatar and Lebanon. Initially, 175 patient samples were recruited from Lebanon, and from previous studies in Qatar. DNA extraction was performed on blood and saliva samples from Qatar, using Invitrogen gDNA and prepIT protocols, respectively. Nanodrop 2000c spectrophotometer was utilized to assess DNA quality, purity, and quantity. In this study, a total of 89 samples underwent Whole Exome Sequencing (WES). Quality assessment before and after WES was performed. Results of WES were uploaded into Franklin by Geenox, and filtration of variants was conducted. Due to time limitations, analysis for only 30 samples was completed, through two different approaches. The systematic analysis approach that relied on a list of genes previously implicated in AF, and resulted in eighteen variants identified in ten genes that were in the list of genes previously implicated in AF. These genes were CAV3, ZFHX3, KCNA5, SYNE2, SCN10A, SCN5A, KCNH2, GATA5, SCN2B, and ANK2. The unbiased approach relied on software, tools, and clinical judgment. It yielded 30.2% of variants related to AF, 32.4% of uncertain relation and significance to AF, and 37.4% unrelated to AF. The lack of parental genomic data represents a significant limitation, restricting the ability to confirm the pathogenicity of identified variants in AF. This study is the first to unravel the genetic underpinnings of AF in the Arab region through WES, addressing a significant gap in AF genetic studies. It marks a significant advancement in understanding the genetic basis of AF within the Arab population, paving the way for future research on AF genetic predisposition in the region.

Date of Award	2025
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences