AUTHOR=Akawi Nadia , Al Mansoori Ghadeera , Al Zaabi Anwar , Badics Andrea , Al Dhaheri Noura , Al Shamsi Aisha , Al Tenaiji Amal , Alzohily Bashar , Almesmari Fatmah S. A. , Al Hammadi Hamad , Al Dhahouri Nahid , Irshaid Manal , Kizhakkedath Praseetha , Al Shibli Fatema , Tabouni Mohammed , Allam Mushal , Baydoun Ibrahim , Alblooshi Hiba , Ali Bassam R. , Foo Roger S. , Al Jasmi Fatma TITLE=Profiling genetic variants in cardiovascular disease genes among a Heterogeneous cohort of Mendelian conditions patients and electronic health records JOURNAL=Frontiers in Molecular Biosciences VOLUME=11 YEAR=2024 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1451457 DOI=10.3389/fmolb.2024.1451457 ISSN=2296-889X ABSTRACT=Introduction

This study addresses the rising cardiovascular disease (CVD) rates in the United Arab Emirates (UAE) by investigating the occurrence and impact of genetic variants in CVD-related genes.

Methods

We collected all genes linked to heritable CVD from public and diagnostic databases and mapped them to their corresponding biological processes and molecular pathways. We then evaluated the types and burden of genetic variants within these genes in 343 individuals from the Emirati Mendelian Study Cohort and 3,007 national electronic health records.

Results

We identified a total of 735 genes associated with heritable CVD, covering a range of cardiovascular conditions. Enrichment analysis revealed key biological processes and pathways, including Apelin, FoxO, and Ras signaling, that are implicated across all forms of heritable CVD. Analysis of a UAE cohort of 3,350 individuals showed a predominance of rare and unique CVD variants specific to the population. The study found a significant burden of pathogenic variants in families with CVD within the Emirati Mendelian cohort and re-assessed the pathogenicity of 693 variants from national health records, leading to the discovery of new CVD-causing variants.

Discussion

This study underscores the importance of continuously updating our understanding of genes and pathways related to CVD. It also highlights the significant underrepresentation of the UAE population in public databases and clinical literature on CVD genetics, offering valuable insights that can inform future research and intervention strategies.