TY - JOUR
T1 - The impact of susceptibility loci for coronary artery disease on other vascular domains and recurrence risk
AU - Tragante, Vinicius
AU - Doevendans, Pieter A. F. M.
AU - Nathoe, Hendrik M.
AU - van der Graaf, Yolanda
AU - Spiering, Wilko
AU - Algra, Ale
AU - de Borst, Gert Jan
AU - de Bakker, Paul I. W.
AU - Asselbergs, Folkert W.
PY - 2013/10/1
Y1 - 2013/10/1
N2 - AimsGenome-wide association studies (GWAS) have identified many genetic loci related to coronary artery disease (CAD) and myocardial infarction (MI). However, the extent to which these loci are related to other vascular diseases is not clear. The aim of this study is to investigate the cumulative effects of risk alleles associated with CAD/MI on ischaemic stroke (IS), abdominal aortic aneurysm (AAA), and peripheral artery disease (PAD).Methods and resultsWe calculated a multi-locus genetic risk score (GRS) in 8446 participants of the SMART (Second Manifestations of ARTerial disease) study based on the lead single-nucleotide polymorphisms (SNPs) at 30 CAD/MI loci, and tested this GRS for cross-sectional association with CAD/MI, IS, AAA and PAD, adjusting for age and sex. We also investigated whether this GRS was associated with recurrent vascular events using Cox regression, adjusting for age, sex, body mass index, type 2 diabetes, low-density lipoprotein-cholesterol, smoking, and hypertension. We found that the GRS was significantly associated with CAD (P = 1.31 × 10-9), IS (P = 0.030), and PAD (P = 6.93 × 10-04), but not with AAA (P = 0.057). The lead SNP at the 9p21 locus (rs4977574) was associated with all four vascular diseases (P < 4 × 10-3), illustrating the functional pleiotropy of this locus. The GRS was associated with recurrent risk of MI (P = 0.026), with a hazard ratio of 1.13 (95% CI 1.00-1.28) for individuals in the top quartile of the GRS distribution (n = 30 recurrent events) compared with those in the bottom quartile (n = 8 recurrent events). Finally, we found a significant positive relationship between the GRS and the number of vascular events (P = 3.26 × 10-05). ConclusionsThese findings suggest that CAD/MI-associated risk alleles play an aetiological role in different types of atherosclerotic disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013.
AB - AimsGenome-wide association studies (GWAS) have identified many genetic loci related to coronary artery disease (CAD) and myocardial infarction (MI). However, the extent to which these loci are related to other vascular diseases is not clear. The aim of this study is to investigate the cumulative effects of risk alleles associated with CAD/MI on ischaemic stroke (IS), abdominal aortic aneurysm (AAA), and peripheral artery disease (PAD).Methods and resultsWe calculated a multi-locus genetic risk score (GRS) in 8446 participants of the SMART (Second Manifestations of ARTerial disease) study based on the lead single-nucleotide polymorphisms (SNPs) at 30 CAD/MI loci, and tested this GRS for cross-sectional association with CAD/MI, IS, AAA and PAD, adjusting for age and sex. We also investigated whether this GRS was associated with recurrent vascular events using Cox regression, adjusting for age, sex, body mass index, type 2 diabetes, low-density lipoprotein-cholesterol, smoking, and hypertension. We found that the GRS was significantly associated with CAD (P = 1.31 × 10-9), IS (P = 0.030), and PAD (P = 6.93 × 10-04), but not with AAA (P = 0.057). The lead SNP at the 9p21 locus (rs4977574) was associated with all four vascular diseases (P < 4 × 10-3), illustrating the functional pleiotropy of this locus. The GRS was associated with recurrent risk of MI (P = 0.026), with a hazard ratio of 1.13 (95% CI 1.00-1.28) for individuals in the top quartile of the GRS distribution (n = 30 recurrent events) compared with those in the bottom quartile (n = 8 recurrent events). Finally, we found a significant positive relationship between the GRS and the number of vascular events (P = 3.26 × 10-05). ConclusionsThese findings suggest that CAD/MI-associated risk alleles play an aetiological role in different types of atherosclerotic disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84885350397&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/23828831
U2 - https://doi.org/10.1093/eurheartj/eht222
DO - https://doi.org/10.1093/eurheartj/eht222
M3 - Article
C2 - 23828831
SN - 0195-668X
VL - 34
SP - 2896
EP - 2904
JO - European Heart journal
JF - European Heart journal
IS - 37
ER -