A multi-locus genetic risk score for abdominal aortic aneurysm

Atherosclerosis. 2016 Mar:246:274-9. doi: 10.1016/j.atherosclerosis.2015.12.031. Epub 2016 Jan 5.

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 5.41 years), 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: Abdominal aortic aneurysm; Genetic risk score; Genetics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aorta, Abdominal* / diagnostic imaging
  • Aortic Aneurysm, Abdominal / diagnostic imaging
  • Aortic Aneurysm, Abdominal / genetics*
  • Dilatation, Pathologic
  • Disease Progression
  • Female
  • Genetic Loci*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Models, Genetic
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors
  • Time Factors

Substances

  • Genetic Markers