TY - JOUR
T1 - A multi-locus genetic risk score for abdominal aortic aneurysm
AU - Ye, Zi
AU - Austin, Erin
AU - Schaid, Daniel J.
AU - Kullo, Iftikhar J.
N1 - Publisher Copyright:
© 2015.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - Abdominal aortic aneurysm
KW - Genetic risk score
KW - Genetics
UR - http://www.scopus.com/inward/record.url?scp=84955308330&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955308330&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2015.12.031
DO - 10.1016/j.atherosclerosis.2015.12.031
M3 - Article
C2 - 26820802
AN - SCOPUS:84955308330
SN - 0021-9150
VL - 246
SP - 274
EP - 279
JO - Atherosclerosis
JF - Atherosclerosis
ER -