title: A multi-locus genetic risk score for abdominal aortic aneurysm.
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.
  
  
  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.
authors.affiliation: Division of Cardiovascular Diseases and the Gonda Vascular Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: Zi
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Division of Cardiovascular Diseases and the Gonda Vascular Center, Mayo Clinic, Rochester, MN, USA; Department of Health Science Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Austin
authors.affiliation: Department of Health Science Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Schaid
authors.affiliation: Division of Cardiovascular Diseases and the Gonda Vascular Center, Mayo Clinic, Rochester, MN, USA. Electronic address: kullo.iftikhar@mayo.edu.
authors.forename: Iftikhar J
authors.initials: IJ
authors.lastname: Kullo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging / Q000235:genetics*; D004108:Dilatation, Pathologic; D018450:Disease Progression; D005260:Female; D056426:Genetic Loci; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D005819:Genetic Markers
keywords: Abdominal aortic aneurysm; Genetic risk score; Genetics
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