AIMS: Genome-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 RESULTS: We 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)). CONCLUSIONS: These findings suggest that CAD/MI-associated risk alleles play an aetiological role in different types of atherosclerotic disease.
AIMS: Genome-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 RESULTS: We 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)). CONCLUSIONS: These findings suggest that CAD/MI-associated risk alleles play an aetiological role in different types of atherosclerotic disease.
Authors: Yisong Huang; Miina Ollikainen; Maheswary Muniandy; Shaoyong Su; James Wilson; Harold Snieder; Jaakko Kaprio; Xiaoling Wang; Tao Zhang; Jenny van Dongen; Guang Hao; Peter J van der Most; Yue Pan; Natalia Pervjakova; Yan V Sun; Qin Hui; Jari Lahti; Eliza Fraszczyk; Xueling Lu; Dianjianyi Sun; Melissa A Richard; Gonneke Willemsen; Kauko Heikkila; Irene Mateo Leach; Nina Mononen; Mika Kähönen; Mikko A Hurme; Olli T Raitakari; Amanda J Drake; Markus Perola; Marja-Liisa Nuotio; Yunfeng Huang; Batbayar Khulan; Katri Räikkönen; Bruce H R Wolffenbuttel; Alexandra Zhernakova; Jingyuan Fu; Haidong Zhu; Yanbin Dong; Jana V van Vliet-Ostaptchouk; Lude Franke; Johan G Eriksson; Myriam Fornage; Lili Milani; Terho Lehtimäki; Viola Vaccarino; Dorret I Boomsma; Pim van der Harst; Eco J C de Geus; Veikko Salomaa; Shengxu Li; Wei Chen Journal: Hypertension Date: 2020-06-10 Impact factor: 10.190
Authors: Christopher Labos; Sara C Martinez; Rui Hao Leo Wang; Petra A Lenzini; Louise Pilote; Peter Bogaty; James M Brophy; James C Engert; Sharon Cresci; George Thanassoulis Journal: Atherosclerosis Date: 2015-07-17 Impact factor: 5.162
Authors: Eythor Bjornsson; Daniel F Gudbjartsson; Anna Helgadottir; Thorarinn Gudnason; Tomas Gudbjartsson; Kristjan Eyjolfsson; Riyaz S Patel; Nima Ghasemzadeh; Gudmar Thorleifsson; Arshed A Quyyumi; Unnur Thorsteinsdottir; Gudmundur Thorgeirsson; Kari Stefansson Journal: Arterioscler Thromb Vasc Biol Date: 2015-04-16 Impact factor: 8.311
Authors: J L Mega; N O Stitziel; S Kathiresan; M S Sabatine; J G Smith; D I Chasman; M Caulfield; J J Devlin; F Nordio; C Hyde; C P Cannon; F Sacks; N Poulter; P Sever; P M Ridker; E Braunwald; O Melander Journal: Lancet Date: 2015-03-04 Impact factor: 79.321
Authors: Vincent G Haver; Niek Verweij; John Kjekshus; Jayne C Fox; Hans Wedel; John Wikstrand; Wiek H van Gilst; Rudolf A de Boer; Dirk J van Veldhuisen; Pim van der Harst Journal: BMC Med Genet Date: 2014-12-21 Impact factor: 2.103