Abstract
Background
We investigated whether a multi-locus genetic risk scores (GRS) was associated with
presence and progression of abdominal aortic aneurysm (AAA) in a case - control study.
Methods and Results
The study comprised of 1124 patients with AAA (74 ± 8 years, 83% men, 52% of them
with a maximal AAA size ≤ 5 cm) and 6524 non-cases (67 ± 11 years, 58% men) from the
Mayo Vascular Disease Biorepository. AAA was defined as infrarenal abdominal aorta
diameter ≥3.0 cm or history of AAA repair. Non-cases were participants without known
AAA. A GRS was calculated using 4 SNPs associated with AAA at genome-wide significance
(P ≤ 10−8). The GRS was associated with the presence of AAA after adjustment for age, sex,
cardiovascular risk factors, atherosclerotic cardiovascular diseases and family history
of aortic aneurysm: odds ratio (OR, 95% confidence interval, CI) 1.06 (1.04–1.09,
p < 0.001). Adding GRS to conventional risk factors improved the association of presence
of AAA (net reclassification index 14%, p < 0.001). In a subset of patients with AAA
who had ≥2 imaging studies (n = 651, mean (SE) growth rate 2.47 (0.11) mm/year during
a mean time interval of 5.41years), GRS, baseline size, diabetes and family history
were each associated with aneurysm growth rate in univariate association (all p < 0.05).
The estimated mean aneurysm growth rate was 0.50 mm/year higher in those with GRS > median
(5.78) than those with GRS ≤ median (p = 0.01), after adjustment for baseline size (p < 0.001), diabetes (p = 0.046) and
family history of aortic aneurysm (p = 0.02).
Conclusions
A multi-locus GRS was associated with presence of AAA and greater aneurysm expansion.
Keywords
Abbreviations:
AAA (abdominal aortic aneurysm), ASCVD (atherosclerotic cardiovascular disease), CHD (coronary heart disease), CI (confidence interval), EHR (electronic health record), GWAS (Genome-wide association studies), OR (odds ratio), SNP (Single nucleotide polymorphism), T2D (Type 2 diabetes)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: January 05, 2016
Accepted:
December 21,
2015
Received in revised form:
October 2,
2015
Received:
May 28,
2015
Identification
Copyright
© 2015 Published by Elsevier Inc.
