Genomewide Association Studies of Stroke

Ikram, M. Arfan; Seshadri, Sudha; Bis, Joshua C.; Fornage, Myriam; DeStefano, Anita L.; Aulchenko, Yurii S.; Debette, Stéphanie; Lumley, Thomas; Folsom, Aaron R.; Herik, Evita G. van den; Bos, Michiel J.; Beiser, Alexa; Cushman, Mary; Launer, Lenore J.; Shahar, Eyal; Struchalin, Maksim; Du, Yangchun; Glazer, Nicole L.; Rosamond, Wayne D.; Rivadeneira, Fernando; Kelly-Hayes, Margaret; López, Oscar L.; Coresh, Josef; Hofman, Albert; DeCarli, Charles; Heckbert, Susan R.; Koudstaal, Peter J.; Yang, Qiong; Smith, Nicholas L.; Kase, Carlos S.; Rice, Kenneth; Haritunians, Talin; Roks, Gerwin; Kort, Paul L.M. de; Taylor, Kent D.; Lau, Lonneke Ml de; Oostra, Ben A.; Uitterlinden, André G.; Rotter, Jerome I.; Boerwinkle, Eric; Psaty, Bruce M.; Mosley, Thomas H.; Duijn, Cornelia M. van; Breteler, Monique M.B.; Longstreth, W. T.; Wolf, Philip A.

doi:10.1056/nejmoa0900094

Cited by 409 publications

(261 citation statements)

References 37 publications

Supporting

Mentioning

241

Contrasting

Unclassified

Order By: Relevance

“…However, the association of variants on chromosome 9p21.3 with ischemic stroke has not been fully verified. Several studies found a positive association [10,11,12,13,14,15,16], but results have been inconsistent [8,9,17,18,19,20] leading to uncertainty about this relationship [21]. …”

Section: Introductionmentioning

confidence: 99%

Exploration of a Hypothesized Independent Association of a Common 9p21.3 Gene Variant and Ischemic Stroke in Patients with and without Angiographic Coronary Artery Disease

Plant

Samsa

Shah³

et al. 2010

Cerebrovasc Dis

View full text Add to dashboard Cite

Background: Single-nucleotide polymorphisms (SNPs) at the chromosome 9p21.3 locus are associated with coronary artery disease (CAD). An association of this genomic region with ischemic stroke independent of its effect on CAD could suggest an additional, stroke-specific pathophysiological relationship. Methods: Medical record review was used to identify 548 patients without a history of cerebrovascular disease and 232 who had a verified ischemic stroke or transient ischemic attack (TIA) from the Duke CATHGEN biorepository of patients who had a cardiac catheterization. ANCOVA and multivariable logistic regression modeling were performed to determine independent genetic associations between the key chromosome 9p21.3 SNP, rs10757278, and ischemic stroke by comparing allele frequencies between 229 patients with stroke or TIA and an equal number of matched nonstroke controls, adjusting for other risk factors. In a secondary analysis, controls were further divided based on the presence (n = 353) or absence (n = 195) of angiographic CAD. Results: Allele frequencies were similar between patients with and without a history of ischemic stroke in both additive (p = 0.83) and dominant (p = 0.92) models of genetic risk. There was no association between rs10757278 allele frequency and stroke status based on the presence or absence of angiographically demonstrated CAD in nonstroke controls (ANCOVA, p = 0.99). Conclusion: These results provide no evidence of a stroke-specific association of the 9p21.3 locus regardless of the presence or absence of angiographic CAD and highlight the need for larger studies to further evaluate this hypothesized relationship.

show abstract

Section: Introductionmentioning

confidence: 99%

Exploration of a Hypothesized Independent Association of a Common 9p21.3 Gene Variant and Ischemic Stroke in Patients with and without Angiographic Coronary Artery Disease

Plant

Samsa

Shah³

et al. 2010

Cerebrovasc Dis

View full text Add to dashboard Cite

show abstract

“…Since 2010, a total of 5,970 DNA samples have been registered belonging to patients (2,688) and controls (3,282). The mean ages of patients and controls were 64.6 ± 19.3 and 56.9 ± 14.9 years, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Genome-wide association study approaches have been adopted for investigating many complex diseases, such as stroke, and have been effective in identifying new genetic variants associated with the risk of disease. However, for stroke studies, genome-wide association studies have so far been applied principally in European, North American and Japanese populations 3,23 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Joinville stroke biobank: study protocol and first year’s results

Ferreira¹,

França²,

Nagel³

et al. 2017

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

Aiming to contribute to studies that use detailed clinical and genomic information of biobanks, we present the initial results of the first Latin American Stroke Biobank. Methods: Blood samples were collected from patients included in the Joinville Stroke Registry and four Brazilian cities. Demographic socio-economic data, cardiovascular risk factors, Causative Classification System for Ischemic Stroke, Trial of Org 10172 in Acute Stroke Treatment and National Institutes of Health scores, functional stroke status (modified Rankin) and brain images were recorded. Additionally, controls from both geographic regions were recruited. High-molecular-weight genomic DNA was obtained from all participants. Results: A total of 2,688 patients and 3,282 controls were included. Among the patients, 76% had ischemic stroke, 12% transient ischemic attacks, 9% hemorrhagic stroke and 3% subarachnoid hemorrhage. Patients with undetermined ischemic stroke were most common according the Trial of Org 10172 in Acute Stroke Treatment (40%) and Causative Classification System for Ischemic Stroke (47%) criteria. A quarter of the patients were under 55 years of age at the first-ever episode. Conclusions: We established the Joinville Stroke Biobank and discuss its potential for contributing to the understanding of the risk factors leading to stroke.

show abstract

“…With regard to stroke prevalence, about 85% is IS, 9% is ICH, and 4% to 5% is due to SAH (Petrea et al, 2009). Environmental factors, such as hypertension, diabetes mellitus, and cigarette smoking, contribute to the risk of stroke, and several lines of evidence indicate that genetic factors are also involved in the development of stroke (Gil-Núñez, 2007;Grysiewicz et al, 2008;Ikram et al, 2009;Lanktree et al, 2010;Matarin et al, 2007). Several candidate genes for the susceptibility to stroke have been studied.…”

Section: Introductionmentioning

confidence: 99%

A Promoter SNP (rs1800682, -670C/T) of FAS Is Associated with Stroke in a Korean Population

Kang¹,

Chung²,

Kim³

et al. 2010

Genomics & Informatics

View full text Add to dashboard Cite

The Fas (TNF receptor superfamily, member 6) (FAS)/ FAS ligand (FASLG) interaction plays a central role in the regulation of programmed cell death. FAS and FASLG polymorphisms in promoter regions affect transcriptional activities. To investigate whether FAS and FASLG polymorphisms are associated with the development and clinical phenotypes of stroke, 2 promoter single nucleotide polymorphisms (SNPs) in FAS (rs1800682, −670C/T) and FASLG (rs763110, −844C/T) were selected and genotyped by direct sequencing in 220 stroke patients [107 ischemic stroke (IS), 77 intracerebral hemorrhage (ICH), and 36 subarachnoid hemorrhage (SAH)] and 369 control subjects. For the analysis of clinical symptoms, all stroke patients were divided into 3 clinical phenotypes according to the respective results of the National Institutes of Health Stroke Survey (NIHSS) and the Modified Barthel Index (MBI) and the presence or absence of complex regional pain syndrome (CRPS). The SNPStats, SNPAnalyzer, and Helixtree programs were used to analyze the genetic data. Multiple logistic regression models (codominant, dominant, and recessive) were used to estimate odds ratios (ORs), 95% confidence intervals (CIs), and p-values. The promoter SNP rs1800682 was associated with stroke in the codominant (OR=0.48, 95% CI=0.25-0.94, p=0.04) and dominant models (OR=0.51, 95% CI=0.30-0.87, p=0.011). However, a FASLG SNP (rs763110) was not in Hardy-Weinberg equilibrium (p＜0.05). In the analysis of stroke types, rs1800682 was associated with IS in the codominant (OR=0.30, 95% CI=0.12-0.74, p=0.025), dominant (OR=0.44, p=0.018), and recessive models (OR=0.45, 95% CI=0.21-0.99, p=0.042).The genotype frequencies of rs1800682 were different between ICH and controls in the dominant model (OR=0.49, 95% CI=0.26-0.94, p=0.031) but not between SAH and controls. In the analysis of clinical symptoms, however, rs1800682 was not related to the 3 clinical phenotypes (NIHSS, MBI, and CRPS). These results suggest that a promoter SNP (rs1800682, −670C/T) in FAS may be associated with the development of stroke in the Korean population.

show abstract

Genomewide Association Studies of Stroke

Abstract: BACKGROUND-The genes underlying the risk of stroke in the general population remain undetermined.

Cited by 409 publications

References 37 publications

Exploration of a Hypothesized Independent Association of a Common 9p21.3 Gene Variant and Ischemic Stroke in Patients with and without Angiographic Coronary Artery Disease

Exploration of a Hypothesized Independent Association of a Common 9p21.3 Gene Variant and Ischemic Stroke in Patients with and without Angiographic Coronary Artery Disease

Joinville stroke biobank: study protocol and first year’s results

A Promoter SNP (rs1800682, -670C/T) of FAS Is Associated with Stroke in a Korean Population

Contact Info

Product

Resources

About