A multi-locus genetic risk score for abdominal aortic aneurysm

Zi Ye, Erin Austin, Daniel J Schaid, Iftikhar Jan Kullo

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)274-279
Number of pages6
JournalAtherosclerosis
Volume246
DOIs
StatePublished - Mar 1 2016

Fingerprint

Genetic Loci
Abdominal Aortic Aneurysm
Aortic Aneurysm
Abdominal Aorta
Vascular Diseases
Aneurysm
Single Nucleotide Polymorphism
Case-Control Studies
Cardiovascular Diseases
Odds Ratio
Genome
Confidence Intervals

Keywords

  • Abdominal aortic aneurysm
  • Genetic risk score
  • Genetics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

A multi-locus genetic risk score for abdominal aortic aneurysm. / Ye, Zi; Austin, Erin; Schaid, Daniel J; Kullo, Iftikhar Jan.

In: Atherosclerosis, Vol. 246, 01.03.2016, p. 274-279.

Research output: Contribution to journalArticle

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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.",
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