TY - JOUR
T1 - Impact of carotid atherosclerosis loci on cardiovascular events
AU - Hemerich, Daiane
AU - van der Laan, Sander W.
AU - Tragante, Vinicius
AU - den Ruijter, Hester M.
AU - de Borst, Gert Jan
AU - Pasterkamp, Gerard
AU - de Bakker, Paul I W
AU - Asselbergs, Folkert W.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Background: Genome-wide association studies (GWAS) have identified six single-nucleotide polymorphisms (SNPs) related to carotid intima media thickness (cIMT) or plaque. However, whether these loci relate to other vascular diseases and subsequent vascular events is unclear. Methods and results: We tested six SNPs (rs4888378, rs11781551, rs445925, rs6601530, rs17398575 and rs1878406) for association with subclinical atherosclerotic measures (cIMT, plaque presence and ankle-brachial index), as well as ischemic stroke, abdominal aortic aneurysm, peripheral or coronary artery disease (CAD) in the Second Manifestations of ARTerial disease (SMART) cohort. Four SNPs were associated with cIMT and two with plaque (p < 0.05). One SNP was also significantly associated to CAD (rs1878406, OR = 1.24, 95% CI = 1.08-1.42, p = 2 × 10-3). A genetic risk score (GRS) based on the cIMT-related SNPs was associated to increased risk of cIMT itself (p = 1 × 10-3), but not to other secondary outcomes or vascular events during follow-up (p = 0.86). Conclusions: In addition to replicating previously published associations for cIMT, we confirmed a nominally significant effect between the GRS and cIMT.
AB - Background: Genome-wide association studies (GWAS) have identified six single-nucleotide polymorphisms (SNPs) related to carotid intima media thickness (cIMT) or plaque. However, whether these loci relate to other vascular diseases and subsequent vascular events is unclear. Methods and results: We tested six SNPs (rs4888378, rs11781551, rs445925, rs6601530, rs17398575 and rs1878406) for association with subclinical atherosclerotic measures (cIMT, plaque presence and ankle-brachial index), as well as ischemic stroke, abdominal aortic aneurysm, peripheral or coronary artery disease (CAD) in the Second Manifestations of ARTerial disease (SMART) cohort. Four SNPs were associated with cIMT and two with plaque (p < 0.05). One SNP was also significantly associated to CAD (rs1878406, OR = 1.24, 95% CI = 1.08-1.42, p = 2 × 10-3). A genetic risk score (GRS) based on the cIMT-related SNPs was associated to increased risk of cIMT itself (p = 1 × 10-3), but not to other secondary outcomes or vascular events during follow-up (p = 0.86). Conclusions: In addition to replicating previously published associations for cIMT, we confirmed a nominally significant effect between the GRS and cIMT.
KW - Atherosclerosis
KW - Carotid intima-media thickness
KW - Plaque
KW - Single-nucleotide polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=84946236335&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2015.10.017
DO - 10.1016/j.atherosclerosis.2015.10.017
M3 - Article
AN - SCOPUS:84946236335
SN - 0021-9150
VL - 243
SP - 466
EP - 468
JO - Atherosclerosis
JF - Atherosclerosis
IS - 2
ER -