A multi-locus genetic risk score for abdominal aortic aneurysm



      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).


      A multi-locus GRS was associated with presence of AAA and greater aneurysm expansion.



      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)
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        • Go A.S.
        • et al.
        Heart disease and stroke statistics–2014 update: a report from the american heart association.
        Circulation. 2014; 129: e28-e292
        • Pande R.L.
        • Beckman J.A.
        Abdominal aortic aneurysm: populations at risk and how to screen.
        J. Vasc. Interv. Radiol. 2008; 19: S2-8
        • Nordon I.M.
        • Hinchliffe R.J.
        • Loftus I.M.
        • Thompson M.M.
        Pathophysiology and epidemiology of abdominal aortic aneurysms.
        Nat. Rev. Cardiol. 2011; 8: 92-102
        • Guirguis-Blake J.M.
        • Beil T.L.
        • Senger C.A.
        • Whitlock E.P.
        Ultrasonography screening for abdominal aortic aneurysms: a systematic evidence review for the u.S. Preventive services task force.
        Ann. Intern Med. 2014; 160: 321-329
        • Powell J.T.
        • Greenhalgh R.M.
        Multifactorial inheritance of abdominal aortic aneurysm.
        Eur. J. Vasc. Surg. 1987; 1: 29-31
        • Bown M.J.
        • et al.
        Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1.
        Am. J. Hum. Genet. 2011; 89: 619-627
        • Bradley D.T.
        • et al.
        A variant in LDLR is associated with abdominal aortic aneurysm.
        Circ. Cardiovasc Genet. 2013; 6: 498-504
        • Elmore J.R.
        • et al.
        Identification of a genetic variant associated with abdominal aortic aneurysms on chromosome 3p12.3 by genome wide association.
        J. Vasc. Surg. 2009; 49: 1525-1531
        • Gretarsdottir S.
        • et al.
        Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm.
        Nat. Genet. 2010; 42: 692-697
        • Helgadottir A.
        • et al.
        The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm.
        Nat. Genet. 2008; 40: 217-224
        • Jones G.T.
        • et al.
        A sequence variant associated with sortilin-1 (sort1) on 1p13.3 is independently associated with abdominal aortic aneurysm.
        Hum. Mol. Genet. 2013; 22: 2941-2947
        • Tragante V.
        • et al.
        The impact of susceptibility loci for coronary artery disease on other vascular domains and recurrence risk.
        Eur. Heart J. 2013; 34: 2896-2904
        • Ye Z.
        • Kalloo F.S.
        • Dalenberg A.K.
        • Kullo I.J.
        An electronic medical record-linked biorepository to identify novel biomarkers for atherosclerotic cardiovascular disease.
        Glob. Cardiol. Sci. Pract. 2013; 2013: 82-90
        • Devaraj S.
        • Dodds S.R.
        Ultrasound surveillance of ectatic abdominal aortas.
        Ann. R. Coll. Surg. Engl. 2008; 90: 477-482
        • Freiberg M.S.
        • et al.
        Abdominal aortic aneurysms, increasing infrarenal aortic diameter, and risk of total mortality and incident cardiovascular disease events: 10-year follow-up data from the cardiovascular health study.
        Circulation. 2008; 117: 1010-1017
        • Ding K.
        • Bailey K.R.
        • Kullo I.J.
        Genotype-informed estimation of risk of coronary heart disease based on genome-wide association data linked to the electronic medical record.
        BMC Cardiovasc Disord. 2011; 11: 66
        • Kullo I.J.
        • et al.
        Leveraging informatics for genetic studies: use of the electronic medical record to enable a genome-wide association study of peripheral arterial disease.
        J. Am. Med. Inf. Assoc. 2010; 17: 568-574
      1. State-specific Secondhand Smoke Exposure and Current Cigarette Smoking Among Adults – United States. 2008: 1232-1235 (MMWR Morb Mortal Wkly Rep. 2009;58)
        • LeFevre M.L.
        Screening for abdominal aortic aneurysm: U.S. Preventive services task force recommendation statement.
        Ann. Intern Med. 2014; 161: 281-290
        • Sidloff D.
        • et al.
        Aneurysm global epidemiology study: public health measures can further reduce abdominal aortic aneurysm mortality.
        Circulation. 2014; 129: 747-753
        • McPhee J.T.
        • Hill J.S.
        • Eslami M.H.
        The impact of gender on presentation, therapy, and mortality of abdominal aortic aneurysm in the united states, 2001-2004.
        J. Vasc. Surg. 2007; 45: 891-899
        • Mureebe L.
        • Egorova N.
        • McKinsey J.F.
        • Kent K.C.
        Gender trends in the repair of ruptured abdominal aortic aneurysms and outcomes.
        J. Vasc. Surg. 2010; 51: 9S-13S
        • Kent K.C.
        • et al.
        Analysis of risk factors for abdominal aortic aneurysm in a cohort of more than 3 million individuals.
        J. Vasc. Surg. 2010; 52: 539-548
        • Mega J.L.
        • et al.
        Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials.
        Lancet. 2015 Jun 6; 385: 2264-2271
        • van 't Hof F.N.
        • et al.
        Impact of inherited genetic variants associated with lipid profile, hypertension, and coronary artery disease on the risk of intracranial and abdominal aortic aneurysms.
        Circ. Cardiovasc Genet. 2013; 6: 264-270
        • Schlosser F.J.
        • et al.
        Growth predictors and prognosis of small abdominal aortic aneurysms.
        J. Vasc. Surg. 2008; 47: 1127-1133
        • Sweeting M.J.
        • Thompson S.G.
        • Brown L.C.
        • Powell J.T.
        Meta-analysis of individual patient data to examine factors affecting growth and rupture of small abdominal aortic aneurysms.
        Br. J. Surg. 2012; 99: 655-665
        • Brady A.R.
        • Thompson S.G.
        • Fowkes F.G.
        • Greenhalgh R.M.
        • Powell J.T.
        Abdominal aortic aneurysm expansion: risk factors and time intervals for surveillance.
        Circulation. 2004; 110: 16-21
        • Kullo I.J.
        • et al.
        Return of results in the genomic medicine projects of the emerge network.
        Front. Genet. 2014; 5: 50
        • Kullo I.J.
        • Jarvik G.P.
        • Manolio T.A.
        • Williams M.S.
        • Roden D.M.
        Leveraging the electronic health record to implement genomic medicine.
        Genet. Med. 2013; 15: 270-271