Manara - Qatar Research Repository
Browse
DOCUMENT
jcm-13-01102.pdf (4.35 MB)
DOCUMENT
supp_jcm-2850970-SI.pdf (302.1 kB)
DATASET
supp_SupplementaryTables.xlsx (553.07 kB)
1/0
3 files

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

journal contribution
submitted on 2024-08-06, 11:29 and posted on 2024-08-06, 11:30 authored by Fatima Qafoud, Mohamed Elshrif, Khalid Kunji, Asma Althani, Amar Salam, Jassim Al Suwaidi, Nidal Asaad, Dawood Darbar, Mohamad Saad

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.

Other Information

Published in: Journal of Clinical Medicine
License: https://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.3390/jcm13041102

Funding

Qatar National Research Fund (PPM 03-0322-190036), Personalizing Therapy for Atrial Fibrillation in Qataris.

History

Language

  • English

Publisher

MDPI

Publication Year

  • 2024

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • Qatar Computing Research Institute - HBKU
  • Qatar University
  • Qatar University Health - QU
  • College of Health Sciences - QU HEALTH
  • Hamad Medical Corporation
  • Hamad General Hospital - HMC
  • Al Khor Hospital - HMC

Geographic coverage

Middle East