Projects per year
Abstract / Description of output
There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, D f, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of D f is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of D f and analyse its relationship with CAD. We replicated 5 D f loci and found 4 additional loci with suggestive significance (P < 1e−05) to contribute to D f variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between D f and CAD, and between D f and myocardial infarction (MI), one of CAD’s fatal outcomes. Fine-mapping of D f loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, D f, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC = 0.770 ± 0.001) when comparing with an established risk model, SCORE, (AUC = 0.741 ± 0.002) and extensions thereof leveraging the PRS (AUC = 0.728 ± 0.001). This evidences that D f provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of D f, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.
Keywords / Materials (for Non-textual outputs)
- Genome-Wide Association Study
- Genetic Predisposition to Disease
- Myocardial Infarction/genetics
- Coronary Artery Disease/genetics
- Risk Factors
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Novel Models for Haemodynamics and Transport in Complex Media: Towards Precision Healthcare for Placental Disorders
1/05/20 → 31/10/23
Work Enabled by Edinburgh Clinical Research Facility