Helgadottir, A., Thorleifsson, G., Magnusson, K. P., Grétarsdottir, S., Steinthorsdottir, V., Manolescu, A. et al. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat. Genet. 40, 217-224

deCODE Genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
Nature Genetics (Impact Factor: 29.35). 03/2008; 40(2):217-24. DOI: 10.1038/ng.72
Source: PubMed


Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.

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Available from: Roberto Pola, Oct 08, 2015
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    • "The mediator between 9p21 and downstream genes may be ANRIL, a noncoding RNA in the region, which can alter downstream gene expression [19, 20]. 9p21 has also been found to be associated with coronary calcification levels, abdominal aortic aneurysms, and intracranial aneurysms, suggesting a broader role for this variant in vessel function [21–24]. "
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    ABSTRACT: Coronary artery disease (CAD) is a complex disease driven by myriad interactions of genetics and environmental factors. Traditionally, studies have analyzed only 1 disease factor at a time, providing useful but limited understanding of the underlying etiology. Recent advances in cost-effective and high-throughput technologies, such as single nucleotide polymorphism (SNP) genotyping, exome/genome/RNA sequencing, gene expression microarrays, and metabolomics assays have enabled the collection of millions of data points in many thousands of individuals. In order to make sense of such 'omics' data, effective analytical methods are needed. We review and highlight some of the main results in this area, focusing on integrative approaches that consider multiple modalities simultaneously. Such analyses have the potential to uncover the genetic basis of CAD, produce genomic risk scores (GRS) for disease prediction, disentangle the complex interactions underlying disease, and predict response to treatment.
    Current Cardiology Reports 06/2014; 16(6):488. DOI:10.1007/s11886-014-0488-1 · 1.93 Impact Factor
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    • "AAA is among a number of vascular disorders to be recently associated with a common allelic variant situated on chromosome 9p21 [72, 73]. A significant association between rs10757278-G and the presence of AAA was found (P = 0.03), an effect size completely consistent with that originally reported [73]. "
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    ABSTRACT: Abdominal aortic aneurysm (AAA) is a prevalent and potentially life-threatening disease. Early detection by screening programs and subsequent surveillance has been shown to be effective at reducing the risk of mortality due to aneurysm rupture. The aim of this review is to summarize the developments in the literature concerning the latest biomarkers (from 2008 to date) and their potential screening and therapeutic values. Our search included human studies in English and found numerous novel biomarkers under research, which were categorized in 6 groups. Most of these studies are either experimental or hampered by their low numbers of patients. We concluded that currently no specific laboratory markers allow screeing for the disease and monitoring its progression or the results of treatment. Further studies and studies in larger patient groups are required in order to validate biomarkers as cost-effective tools in the AAA disease.
    BioMed Research International 05/2014; 2014:925840. DOI:10.1155/2014/925840 · 3.17 Impact Factor
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    • "If sufficiently large case-control groups are used, GWAS is an efficient method to identify reproducible risk alleles predisposing to the disease of interest [9, 40]. GWAS has proven a powerful instrument to identify genetic risk factors associated with the presence of cardiovascular disease and has been carried out by international consortia to identify susceptibility loci for AAA [28, 41–44]. "
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    ABSTRACT: An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta with a diameter of at least 3.0 cm. AAAs are often asymptomatic and are discovered as incidental findings in imaging studies or when the AAA ruptures leading to a medical emergency. AAAs are more common in males than females, in individuals of European ancestry, and in those over 65 years of age. Smoking is the most important environmental risk factor. In addition, a positive family history of AAA increases the person's risk for AAA. Interestingly, diabetes has been shown to be a protective factor for AAA in many large studies. Hallmarks of AAA pathogenesis include inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. Autoimmunity may also play a role in AAA development and progression. In this Outlook paper, we summarize our recent studies on AAA including clinical studies related to surgical repair of AAA and genetic risk factor and large-scale gene expression studies. We conclude with a discussion on our research projects using large data sets available through electronic medical records and biobanks.
    04/2014; 2014:564734. DOI:10.1155/2014/564734
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