Ischemic Heart Disease Clinical Trial
Official title:
The National Heart Centre Singapore Prospective CABG Cohort: Multi- Level and Integrated Analysis of Mechanisms Underlying Atrial Dysfunction
Integrated and cross-disciplinary analysis of human physiology and disease provides unbiased
and deeply informative insights into human health and disease. In this study the
investigators will recruit patients undergoing coronary artery bypass surgery to study the
atrium of the heart or the aortic wall that when diseased can cause strokes.
Hypothesis: Systems-level analysis of the left atrium and aorta cells that integrates
imaging, histological, cellular and molecular data will identify new mechanism for
cardiovascular form and function.
While there are many sub-aims to this study, the overarching goal is to define molecular
mechanisms underlying atrial dysfunction. Here the investigator provide a power calculation
based on detecting the genetic control points of gene expression (eQTLs) in the human atrial
fibroblast. The investigator and many others have shown that tissue-specific eQTLs can be
robustly identified at genome-wide significance in segregating populations of ~200. In this
study the investigator propose eQTL association analysis in humans, which have previously
been successfully performed in cohorts of less than 1000 subjects. The general applicability
of this approach has been validated in multiple studies across multiple tissues in cohorts
of between 200-1000 subjects.Based on published imaging genetic studies that have been
successfully applied in small cohorts (<500) and the success of echo-based,
semi-quantitative studies of ventricular dimensions, the investigator are confident that our
quantitative studies of 750 individuals are powered to detect genome wide significant loci
for the traits under study.
Despite intensive research there is a critical gap in our knowledge in the mechanisms
underlying atrial fibrillation, which is a major cause of stroke and heart failure and
increasingly common as it is a disease of the elderly. This project will address this
important gap in our knowledge and provide new insights into disease pathogenesis with the
goal of stratifying participants to prevent strokes and for treating the underlying
substrate.
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