Table1_Profiling genetic variants in cardiovascular disease genes among a Heterogeneous cohort of Mendelian conditions patients and electronic health records.XLSX

IntroductionThis 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.MethodsWe 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.ResultsWe 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.DiscussionThis 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.

引言本项研究旨在探讨阿拉伯联合酋长国（UAE）心血管疾病（CVD）发病率上升的现状，通过研究CVD相关基因中的遗传变异的发生及其影响。方法我们收集了所有与遗传性CVD相关的基因，并从公共和诊断数据库中映射它们对应的生物学过程和分子通路。随后，我们在343名来自阿联酋孟德尔研究队列的个体和3,007份国家电子健康记录中评估了这些基因内遗传变异的类型和负担。结果我们鉴定出总共735个与遗传性CVD相关的基因，涵盖了多种心血管疾病。富集分析揭示了关键的生物学过程和通路，包括Apelin、FoxO和Ras信号通路，这些通路在所有遗传性CVD形式中均有涉及。对3,350名阿联酋个体的队列分析显示，罕见且独特的CVD变异在该人群中占主导地位。研究发现在阿联酋孟德尔队列中CVD家族存在显著的致病性变异负担，并对国家健康记录中的693个变异的致病性进行了重新评估，从而发现了新的CVD致病变异。讨论本研究强调了持续更新我们对与CVD相关的基因和通路理解的重要性。同时，它也突显了阿联酋人口在公共数据库和CVD遗传学临床文献中的代表性不足，提供了对未来研究和干预策略具有价值的见解。