Dataset Information

Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12.

ABSTRACT:

Objectives

To perform a genome-wide association study (GWAS) using the Immunochip array in 3,420 cases of ischemic stroke and 6,821 controls, followed by a meta-analysis with data from more than 14,000 additional ischemic stroke cases.

Methods

Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 cases and 5,972 controls recruited from the ischemic stroke WTCCC2 study, and with summary statistics from a further 8,480 cases and 56,032 controls in the METASTROKE consortium. A final in silico "look-up" of 2 single nucleotide polymorphisms in 2,522 cases and 1,899 controls was performed. Associations were also examined in 1,088 cases with intracerebral hemorrhage and 1,102 controls.

Results

In an overall analysis of 17,970 cases of ischemic stroke and 70,764 controls, we identified a novel association on chromosome 12q24 (rs10744777, odds ratio [OR] 1.10 [1.07-1.13], p = 7.12 × 10(-11)) with ischemic stroke. The association was with all ischemic stroke rather than an individual stroke subtype, with similar effect sizes seen in different stroke subtypes. There was no association with intracerebral hemorrhage (OR 1.03 [0.90-1.17], p = 0.695).

Conclusion

Our results show, for the first time, a genetic risk locus associated with ischemic stroke as a whole, rather than in a subtype-specific manner. This finding was not associated with intracerebral hemorrhage.

SUBMITTER: Kilarski LL

PROVIDER: S-EPMC4150131 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Publications

Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12.

Kilarski Laura L LL Achterberg Sefanja S Devan William J WJ Traylor Matthew M Malik Rainer R Lindgren Arne A Pare Guillame G Sharma Pankaj P Slowik Agniesczka A Thijs Vincent V Walters Matthew M Worrall Bradford B BB Sale Michele M MM Algra Ale A Kappelle L Jaap LJ Wijmenga Cisca C Norrving Bo B Sandling Johanna K JK Rönnblom Lars L Goris An A Franke Andre A Sudlow Cathie C Rothwell Peter M PM Levi Christopher C Holliday Elizabeth G EG Fornage Myriam M Psaty Bruce B Gretarsdottir Solveig S Thorsteinsdottir Unnar U Seshadri Sudha S Mitchell Braxton D BD Kittner Steven S Clarke Robert R Hopewell Jemma C JC Bis Joshua C JC Boncoraglio Giorgio B GB Meschia James J Ikram M Arfan MA Hansen Bjorn M BM Montaner Joan J Thorleifsson Gudmar G Stefanson Kari K Rosand Jonathan J de Bakker Paul I W PI Farrall Martin M Dichgans Martin M Markus Hugh S HS Bevan Steve S

Neurology 20140716 8

<h4>Objectives</h4>To perform a genome-wide association study (GWAS) using the Immunochip array in 3,420 cases of ischemic stroke and 6,821 controls, followed by a meta-analysis with data from more than 14,000 additional ischemic stroke cases.<h4>Methods</h4>Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 cases and 5,972 controls recruited from the ischemic stroke WTCCC2 study, and ...[more]

PMID: 25031287

Similar Datasets

Project description:BackgroundIschemic stroke (IS) is a complex polygenic disease with a strong genetic background. The relationship between the ANRIL (antisense non-coding RNA in the INK4 locus) in chromosome 9p21 region and IS has been reported across populations worldwide; however, these studies have yielded inconsistent results. The aim of this study is to clarify the types of single-nucleotide polymorphisms on the ANRIL locus associated with susceptibility to IS using meta-analysis and comprehensively assess the strength of the association.MethodsRelevant studies were identified by comprehensive and systematic literature searches. The quality of each study was assessed using the Newcastle-Ottawa Scale. Allele and genotype frequencies were extracted from each of the included studies. Odds ratios with corresponding 95% confidence intervals of combined analyses were calculated under three genetic models (allele frequency comparison, dominant model, and recessive model) using a random-effects or fixed-effects model. Heterogeneity was tested using the chi-square test based on the Cochran Q statistic and I2 metric, and subgroup analyses and a meta-regression model were used to explore sources of heterogeneity. The correction for multiple testing used the false discovery rate method proposed by Benjamini and Hochberg. The assessment of publication bias employed funnel plots and Egger's test.ResultsWe identified 25 studies (15 SNPs, involving a total of 11,527 cases and 12,216 controls maximum) and performed a meta-analysis. Eight SNPs (rs10757274, rs10757278, rs2383206, rs1333040, rs1333049, rs1537378, rs4977574, and rs1004638) in ANRIL were significantly associated with IS risk. Six of these SNPs (rs10757274, rs10757278, rs2383206, rs1333040, rs1537378, and rs4977574) had a significant relationship to the large artery atherosclerosis subtype of IS. Two SNPs (rs2383206 and rs4977574) were associated with IS mainly in Asians, and three SNPs (rs10757274, rs1333040, and rs1333049) were associated with susceptibility to IS mainly in Caucasians. Sensitivity analyses confirmed the reliability of the original results. Ethnicity and individual studies may be the main sources of heterogeneity in ANRIL.ConclusionsOur results suggest that some single-nucleotide polymorphisms on the ANRIL locus may be associated with IS risk. Future studies with larger sample numbers are necessary to confirm this result. Additional functional analyses of causal effects of these polymorphisms on IS subtypes are also essential.

Dataset Information

Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12.

Objectives

Methods

Results

Conclusion

Publications

Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12.

Similar Datasets

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