thesis_access.pdf (2.19 MB)
Download file

The Clinical Utility of Genetic Risk Scores Following Myocardial Infarction

Download (2.19 MB)
thesis
posted on 22.11.2021, 15:31 by Northcott, Hadley

Current risk assessment for the development of coronary artery disease (CAD) in an individual relies on a combination of clinical characteristics. These well-established CAD risk factors include consideration of age, gender, hypertension, dyslipidemia, diabetes, smoking and obesity. However there are a proportion of patients that experience an acute coronary syndrome (ACS) event despite being deemed as low risk based on the current New Zealand risk model. These patients present with an absence of the traditional risk factors, or they fall below the age threshold where CAD screening is initiated.  The lack of association with disease development and presence of the traditional risk factors in these patients has led to the hypothesis that genetics play a significant role in the etiology of their disease. The conduction of family-based hereditary studies has supported the hypothesis that CAD risk is associated with genetic markers. A method of analyzing this genetic risk has been developed in the form of calculating a genetic risk score (GRS). The GRS is comprised of a panel of single nucleotide polymorphisms (SNPs) discovered through genome wide association studies in CAD patients. Currently, there is controversy in the clinical utility of different GRS calculation methods, and as yet, there has been no research conducted on the potential benefits of a GRS in a New Zealand setting.  Our study measured genetic risk through a weighted GRS calculated from a 27 SNP panel in 420 patients in a New Zealand based population. In looking at whether we could determine a difference in GRS values between premature (young) MI patients and older control patients, we found that the mean GRS was not significantly elevated in the premature MI cohort (p = 0.156). However, in assessing GRS differences between ethnicities and in relation to specific risk factors we saw that mean GRS was higher in patients with a family history of coronary disease (p = 0.003), in Māori patients (p = 0.013) and in patients with fewer than 2 traditional risk features (p = 0.001). GRS was not associated with individual traditional risk factors, including dyslipidaemia, hypertension, diabetes, obesity or gender. Our results showed that genetic risk for CAD is identifiable with this GRS, and indicates that further research into ethnic differences and identifying genetic risk in young CAD patients with low traditional risk would provide interesting insights.

History

Copyright Date

01/01/2016

Date of Award

01/01/2016

Publisher

Te Herenga Waka—Victoria University of Wellington

Rights License

Author Retains Copyright

Degree Discipline

Cardiology

Degree Grantor

Te Herenga Waka—Victoria University of Wellington

Degree Level

Masters

Degree Name

Master of Biomedical Science

ANZSRC Type Of Activity code

970111 Expanding Knowledge in the Medical and Health Sciences

Victoria University of Wellington Item Type

Awarded Research Masters Thesis

Language

en_NZ

Victoria University of Wellington School

School of Biological Sciences

Advisors

Larsen, Peter; Harding, Scott