Zi Ye1, Erin Austin2, Daniel J Schaid3, Iftikhar J Kullo4. 1. Division of Cardiovascular Diseases and the Gonda Vascular Center, Mayo Clinic, Rochester, MN, USA. 2. Division of Cardiovascular Diseases and the Gonda Vascular Center, Mayo Clinic, Rochester, MN, USA; Department of Health Science Research, Mayo Clinic, Rochester, MN, USA. 3. Department of Health Science Research, Mayo Clinic, Rochester, MN, USA. 4. Division of Cardiovascular Diseases and the Gonda Vascular Center, Mayo Clinic, Rochester, MN, USA. Electronic address: kullo.iftikhar@mayo.edu.
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.
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.
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