The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm

Helgadóttir, Anna; Þorleifsson, Guðmar; Magnússon, Kristinn P.; Grétarsdóttir, Sólveig; Steinthórsdóttir, Valgerður; Manolescu, Andrei; Jones, Gregory T.; Rinkel, Gabriël J.E.; Blankensteijn, Jan D.; Ronkainen, Antti; Jääskeläinen, Juha E.; Kyo, Yoshiki; Lenk, Guy M.; Sakalihasan, Natzi; Kostulas, Konstantinos; Gottsäter, Anders; Flex, Andrea; Stefánsson, Hreinn; Hansen, Torben; Andersen, Gitte; Weinsheimer, Shantel; Borch‐Johnsen, Knut; Jørgensen, Torben; Shah, Svati H.; Quyyumi, Arshed A.; Granger, Christopher B.; Reilly, Muredach P.; Austin, Harland; Levey, Aĺlan I.; Vaccarino, Viola; Pálsdóttir, Ebba; Walters, G. Bragi; Jónsdóttir, Þorbjörg; Snorradóttir, Steinunn; Magnusdottir, Dana; Guðmundsson, Guðmundur A.; Ferrell, Robert E.; Sveinbjörnsdóttir, Sigurlaug; Hernesniemi, Juha; Niemelä, Mika; Limet, Raymond; Andersen, Karl; Sigurðsson, Gunnar; Benediktsson, Rafn; Verhoeven, Eric L.G.; Teijink, Joep A.W.; Grobbee, Diederick E.; Rader, Daniel J.; Collier, David; Pedersen, Oluf; Pola, Roberto; Hillert, Jan; Lindblad, Bengt; Valdimarsson, Einar Már; Magnadottir, Hulda B.; Wijmenga, Cisca; Tromp, Gerard; Baas, Annette F.; Ruigrok, Ynte M.; Rij, André M. van; Kuivaniemi, Helena; Powell, J.T.; Matthíasson, Stefán E.; Gulcher, Jeffrey R.; Þorgeirsson, Guðmundur; Kong, Augustine; Þorsteinsdóttir, Unnur; Stefánsson, Kári

doi:10.1038/ng.72

Cited by 651 publications

(586 citation statements)

References 29 publications

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“…Similarly, the association of rs10811661-T allele with T2D does not apply to CAD and other arterial diseases that they have investigated. 42 Although this study confirmed the specificity of the SNP associations to CAD and T2D respectively, it is still unclear whether the two risk alleles residing in the same locus will eventually affect the same gene or functional element leading to a defect or alteration of a biological pathway that is responsible for the diseases. Therefore, the pleiotropic effect of 9p21 locus warrants further investigation.…”

Section: Gwas After Hapmap-the Progress Over the Past 5 Years The Firsupporting

confidence: 62%

“…As the two SNPs are independent, it was unclear at that time whether the SNP that is associated with T2D is also associated with CAD/MI and vice versa. To further investigate this, Helgadottir et al 42 examined the association of these two SNPs with T2D, CAD and four other arterial diseases, and found that rs10757278-G allele is associated with CAD, abdominal aortic aneurysm and intracranial aneurysm, but not with T2D. Similarly, the association of rs10811661-T allele with T2D does not apply to CAD and other arterial diseases that they have investigated.…”

Section: Gwas After Hapmap-the Progress Over the Past 5 Years The Firmentioning

confidence: 99%

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The pursuit of genome-wide association studies: where are we now?

et al. 2010

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It is now 5 years since the first genome-wide association studies (GWAS), published in 2005, identified a common risk allele with large effect size for age-related macular degeneration in a small sample set. Following this exciting finding, researchers have become optimistic about the prospect of the genome-wide association approach. However, most of the risk alleles identified in the subsequent GWAS for various complex diseases are common with small effect sizes (odds ratio o1.5). So far, more than 450 GWAS have been published and the associations of greater than 2000 single nucleotide polymorphisms (SNPs) or genetic loci were reported. The aim of this review paper is to give an overview of the evolving field of GWAS, discuss the progress that has been made by GWAS and some of the interesting findings, and summarize what we have learned over the past 5 years about the genetic basis of human complex diseases. This review will focus on GWAS of SNPs association for complex diseases but not studies of copy number variations.

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Section: Gwas After Hapmap-the Progress Over the Past 5 Years The Firsupporting

confidence: 62%

Section: Gwas After Hapmap-the Progress Over the Past 5 Years The Firmentioning

confidence: 99%

The pursuit of genome-wide association studies: where are we now?

et al. 2010

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“…Recently, genome-wide association studies have demonstrated a locus on chromosome 9p21 for CAD susceptibility in Caucasians (3)(4)(5)(6)(7). Chromosome 9p21 was found to also be associated with other atherosclerotic diseases such as stroke and aneurysm (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Chromosome 9p21 polymorphism is associated with myocardial infarction but not with clinical outcome in Han Chinese

Peng¹,

Lü²,

Zhang³

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: rs1333049 polymorphism on chromosome 9p21 has been shown to affect susceptibility to coronary artery disease (CAD) in Caucasians. This study examined the association of rs1333049 with myocardial infarction (MI), angiographic severity of CAD and clinical outcome after a first acute MI in Han Chinese. Methods: rs1333049 polymorphism was genotyped in 520 patients with a first acute MI and in 560 controls. The number of angiographically documented diseased coronary arteries (luminal diameter stenosis G50%), echocardiographic left ventricular ejection fraction (LVEF), and major adverse cardiac events (MACE) during follow-up (mean, 29"15 months) were recorded. Results: Patients with MI had higher frequencies of the CC genotype (30.0% vs. 20.7%) or C allele (55.5% vs. 46.2%) compared with controls (all p-0.01). rs1333049 polymorphism was strongly associated with MI wodds ratio (OR) 1.48, 95% confidence interval (CI) 1.22-1.79x after adjusting for traditional risk factors. Although longer hospitalization stay was observed in patients with the rs1333049-C allele, this polymorphism was not related to angiographic severity of CAD, LVEF, and occurrence of MACE after MI. Conclusions: This study demonstrates an association of rs1333049 polymorphism locus on chromosome 9p21 with risk for MI, but not with post-MI prognosis in Han Chinese. Clin Chem Lab Med 2009;47:917-22.

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“…An example of the clinical application of SNPs is the recent description of an SNP associated with coronary heart disease (CHD). 14,15 Using appropriate sample sizes, these groups found that homozygous individuals for one specific allele have an B20-40% increased risk of developing CHD and that B20-25% of individuals analyzed are homozygous for this variant. This kind of data can identify subjects with a higher risk for specific diseases, helping to design better strategies for the management of the patients and contributing to decipher the molecular basis of this disease.…”

Section: Discussionmentioning

confidence: 99%

DNA polymorphisms as tools for spinal cord injury research

et al. 2008

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Study Design: Data mining of single nucleotide polymorphisms (SNPs) in gene pathways related to spinal cord injury (SCI). Objectives: To identify gene polymorphisms putatively implicated with neuronal damage evolution pathways, potentially useful to SCI study. Setting: Departments of Psychiatry and Orthopedics, Faculdade de Medicina, Universidade de São Paulo, Brazil. Methods: Genes involved with processes related to SCI, such as apoptosis, inflammatory response, axonogenesis, peripheral nervous system development and axon ensheathment, were determined by evaluating the 'Biological Process' annotation of Gene Ontology (GO). Each gene of these pathways was mapped using MapViewer, and gene coordinates were used to identify their polymorphisms in the SNP database. As a proof of concept, the frequency of subset of SNPs, located in four genes (ALOX12, APOE, BDNF and NINJ1) was evaluated in the DNA of a group of 28 SCI patients and 38 individuals with no SC lesions. Results: We could identify a total of 95 276 SNPs in a set of 588 genes associated with the selected GO terms, including 3912 nucleotide alterations located in coding regions of genes. The five nonsynonymous SNPs genotyped in our small group of patients, showed a significant frequency, reinforcing their potential use for the investigation of SCI evolution. Conclusion: Despite the importance of SNPs in many aspects of gene expression and protein activity, these gene alterations have not been explored in SCI research. Here we describe a set of potentially useful SNPs, some of which could underlie the genetic mechanisms involved in the post trauma spinal cord damage.

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The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm

Cited by 651 publications

References 29 publications

The pursuit of genome-wide association studies: where are we now?

The pursuit of genome-wide association studies: where are we now?

Chromosome 9p21 polymorphism is associated with myocardial infarction but not with clinical outcome in Han Chinese

DNA polymorphisms as tools for spinal cord injury research

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