Evidence for association of A allele of rs660599 (chromosome 11; Base position 102,234,967) with large artery atherosclerotic stroke and all ischaemic stroke.

<p>LAA, large artery stroke; IS, all ischaemic stroke; SNP, single nucleotide polymorphism; RAF, risk allele frequency; OR, odds ratio; 95% CI, 95% confidence interval; EUR, meta-analysis in individuals of European ancestry alone; ALL, trans-ethnic meta-analysis of all individuals. Forest plots of effect sizes and standard errors for each replication centre are given in Figures S3, S4.</p

Sample size of replication populations.

<p>LAA, large artery stroke; IS, all ischaemic stroke; ARIC, the Atherosclerosis Risk in communities study; ASGC, the Australian Stroke Genetics collaboration; deCODE, deCODE genetics; GEOS, the Genetics of early onset stroke study; HVH, the heart and vascular health study; ISGS/SWISS, the Ischaemic stroke genetics study/Siblings with Ischaemic stroke study; MGH-GASROS, Massachusetts General Hospital – Genetics affecting stroke risk and outcome; PROMISe, Prognostic modeling in ischaemic stroke study <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004469#pgen.1004469-Achterberg1" target="_blank">[55]</a>; RACE, Risk Assessment of Cerebrovascular Events study. For further details of these populations please see the original METASTROKE publication <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004469#pgen.1004469-Traylor2" target="_blank">[16]</a>.</p

LocusZoom plot of <i>MMP12</i> association using age-at-onset informed approach.

<p>SNPs are colored based on their correlation (r²) with the labeled top SNP, which has the smallest P value in the region. The fine-scale recombination rates estimated from 1000 Genomes (EUR) data are marked in light blue, with genes marked below by horizontal blue lines. Arrows on the horizontal blue lines show the direction of transcription, and rectangles are exons. SNP p-values are from the discovery meta-analysis only with the exception of rs660599, for which the given p-value indicates the overall evidence for association from the discovery and replication cohorts.</p

Sample size of discovery populations.

<p>IS, all ischaemic stroke; CE, cardioembolic stroke; LAA, large artery stroke; SVD, small vessel disease.</p

Evaluation of evidence genome-wide for SNPs exhibiting greater significance using the age-at-onset informed approach compared to permutations.

<p>-log10(p value) from permutations for evidence of age-at-onset effect at given SNP p-value selection threshold shown in red; median proportion of SNPs (with IQR) more significant in observed age-at-onset informed meta-analysis compared to permutations shown in blue; horizontal line at p = 0.05 in red; horizontal line at median proportion of SNP = 0.5 in blue; IS, all ischaemic stroke; CE, cardioembolic stroke; LAA, large artery atherosclerotic stroke; SVD, small vessel disease. See <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004469#pgen.1004469.s009" target="_blank">Table S5</a> for number of SNPs included at each p-value selection threshold.</p

Regional association plot of SNP rs12155400 on chromosome 7 for Caucasians.

<p>This figure is the regional association plot of SNP rs12155400 on chromosome 7 that reached genome-wide significance in the meta-analysis of GWAS results in participants of European ancestry without diabetes or hypertension. The lead and surrounding SNPs are color coded according to the pair-wise linkage disequilibrium (LD) with the lead SNP (presented as a diamond) on a scale of r² from 0 to 1. Estimated recombination rates reflect the local LD structure in the 500 kb buffer around the index SNP and plotted based on values from HapMap II Centre d’Etude du Polymorphisme Humain collection samples from a Utah (CEU) population.</p

Subject characteristics by study site.

*<p>Sample size of cohort used for primary analysis.</p>†<p>Presented as mean (standard deviation).</p>‡<p>Random glucose. HTN: Current use of blood pressure medication or systolic/diastolic blood pressure ≥140/90. AGES: Age, Gene/Environment Susceptibility-Reykjavik Study. ARIC: Atherosclerosis Risk in Communities study. BMES: Blue Mountains Eye Study. CHS: Cardiovascular Health Study. MESA: Multi-Ethnic Study of Atherosclerosis. RS: Rotterdam Study.</p

Regional association plot of SNP rs10486302 on chromosome 7 for Singapore Asian Indians.

<p>This figure is the regional association plot of SNP rs10486302 on chromosome 7 that reached gene-wide significance (p&lt;4.9×10⁻⁴) in the testing of transferability of the discovery SNP, rs12155400, to other SNPs in the histone deacetylase 9 gene in a cohort of Singapore Asian Indians without diabetes or hypertension. The lead and surrounding SNPs are color coded according to the pair-wise linkage disequilibrium (LD) with the lead SNP (presented as a diamond) on a scale of r² from 0 to 1. Estimated recombination rates reflect the local LD structure in the 500kb buffer around the index SNP and plotted based on values from HapMap II Han Chinese of Beijing China (HCT)/Japanese in Tokyo, Japan (JPT) populations.</p

Regional association plot of SNP rs213276 on chromosome 7 for African Americans.

<p>This figure is the regional association plot of SNP rs213276 on chromosome 7 that reached gene-wide significance (p&lt;5.2×10⁻⁵) in the testing of transferability of the discovery SNP, rs12155400, to other SNPs in the histone deacetylase 9 gene in a cohort of African Americans without diabetes or hypertension. The lead and surrounding SNPs are color coded according to the pair-wise linkage disequilibrium (LD) with the lead SNP (presented as a diamond) on a scale of r² from 0 to 1. Estimated recombination rates reflect the local LD structure in the 500 kb buffer around the index SNP and plotted based on values from HapMap II Yoruba in Ibadan, Nigeria (YRI) population.</p

The association between SNP rs12155400 on chromosome 7 and various micro- and macrovascular diseases.

*<p>The Wellcome Trust Case Control Consortium 2.</p>†<p>The Heart and Vascular Health Study.</p>#<p>No results.</p>‡<p>Chronic Kidney Diseases Genetics Consortium. MAF: Minor Allele Frequency. SE: Standard Error. UACR: Urinary Albumin to Creatinine Ratio. eGFRcrea: estimated Glomerular Filtration Rate using creatinine.</p