Repeated Replication and a Prospective Meta-Analysis of the Association Between Chromosome 9p21.3 and Coronary Artery Disease

Schunkert, Heribert; Götz, Anika; Braund, Peter S.; McGinnis, Ralph; Trégouët, David‐Alexandre; Mangino, Massimo; Linsel-Nitschke, Patrick; Cambien, François; Hengstenberg, Christian; Stark, Klaus; Blankenberg, Stefan; Tiret, Laurence; Ducimetière, Pierre; Keniry, Andrew; Ghori, Mohammed J. R.; Schreiber, Stefan; Mokhtari, Nour Eddine El; Hall, Alistair S.; Dixon, Richard J.; Goodall, Alison H.; Liptau, Henrike; Pollard, Helen Perlstein; Schwarz, Dániel; Hothorn, Ludwig A.; Wichmann, H‐Erich; König, Inke R.; Fischer, Marcus; Meisinger, Christa; Ouwehand, Willem H.; Deloukas, Panos; Thompson, John R.; Erdmann, Jeanette; Ziegler, Andreas; Samani, Nilesh J.

doi:10.1161/circulationaha.107.730614

Cited by 353 publications

(346 citation statements)

References 23 publications

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“…This locus became the first claim of what has later been called a gold rush of CAD genetics. Interestingly, the chromosome 9p21 locus still has an outstanding position as it depicts the genetic variant with the highest population‐attributable risk (Table 2; Schunkert et al , 2008). …”

Section: Genome‐wide Association Studies In Coronary Artery Disease Amentioning

confidence: 99%

The impact of genome‐wide association studies on the pathophysiology and therapy of cardiovascular disease

2016

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Cardiovascular diseases are leading causes for death worldwide. Genetic disposition jointly with traditional risk factors precipitates their manifestation. Whereas the implications of a positive family history for individual risk have been known for a long time, only in the past few years have genome‐wide association studies (GWAS) shed light on the underlying genetic variations. Here, we review these studies designed to increase our understanding of the pathophysiology of cardiovascular diseases, particularly coronary artery disease and myocardial infarction. We focus on the newly established pathways to exemplify the translation from the identification of risk‐related genetic variants to new preventive and therapeutic strategies for cardiovascular disease.

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Section: Genome‐wide Association Studies In Coronary Artery Disease Amentioning

confidence: 99%

The impact of genome‐wide association studies on the pathophysiology and therapy of cardiovascular disease

2016

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“…Although numerous candidate genes have been implicated in the development and progression of atherosclerosis, the genes that are responsible remain largely unknown. 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%

“…Studies on chromosome 9p21 were performed primarily in Caucasians, while similar studies in Asians are less common (7). As variants and their frequencies of chromosome 9p21 in various ethnic groups might be different, replication is needed to confirm the potential effects of chromosome 9p21 in other groups.…”

Section: Introductionmentioning

confidence: 99%

“…However, little data is available regarding the impact of chromosome 9p21 on the prognosis of Asian patients with CAD. The present study was conducted to assess the association of rs1333049 polymorphism, one representative polymorphism on chromosome 9p21 (7), with MI, angiographic severity of CAD, and occurrence of major adverse cardiac events (MACE) after acute MI in Han Chinese.…”

Section: Introductionmentioning

confidence: 99%

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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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“…This technological advance led the Wellcome Trust Case Control Consortium and others to perform SNP-based GWAS on patients with CAD compared with matched controls [23]. The most reproducible locus conferring increased risk of CAD is situated on chromosome 9 (locus 9p21.3) [24][25][26][27], increasing risk by approximately 1.2 for a single copy (1.5 in the 25% of the population who carry two copies) [28]. Interestingly, unlike other regions associated with surrogate risk factors for CAD, such as CRP [29], adiposity [30] and LV mass [31], the 9p21.3 locus does not affect such risk factors, suggesting that it promotes CAD in a non-canonical manner.…”

Section: Genome-wide Association Studies: Getting Closer To the Genetmentioning

confidence: 99%

The genetics of cardiovascular disease: new insights from emerging approaches

Chico¹,

Milo²,

Crossman³

2009

The Journal of Pathology

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The prospect that sequencing the human genome would see rapid translation of a greater understanding of cardiovascular genetics into novel diagnostics and therapeutics has so far met with only limited success. However, diverse technological advances and exploitation of novel animal models of cardiovascular development and disease are providing ever more insight into cardiovascular diseases and development, and bring closer the prospect of 'postgenomic' diagnostics and therapies. Here we review some of these emerging approaches (genome wide association studies, deep sequencing, microRNA regulation, and zebrafish as a model of cardiovascular disease and development) and discuss their potential for finally fulfilling the promise of application to clinical cardiovascular medicine.

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Repeated Replication and a Prospective Meta-Analysis of the Association Between Chromosome 9p21.3 and Coronary Artery Disease

Abstract: This broad replication provides unprecedented evidence for association between genetic variants at chromosome 9p21.3 and risk of CAD.

Cited by 353 publications

References 23 publications

The impact of genome‐wide association studies on the pathophysiology and therapy of cardiovascular disease

The impact of genome‐wide association studies on the pathophysiology and therapy of cardiovascular disease

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

The genetics of cardiovascular disease: new insights from emerging approaches

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