Summary of polymorphisms and classification for the genetic risk score.

<p>Summary of polymorphisms and classification for the genetic risk score.</p

Adjusted association between individual dopamine variants and depressive symptoms.

<p>Cell entries are beta coefficients, standard errors (s.e.), p-values and 95% confidence intervals (CI). The HS model controlled for race/ethnicity.</p

Adjusted association between dopamine score and depressive symptoms.

<p>Cell entries are beta coefficients, standard errors (s.e.), p-values and 95% confidence intervals (CI). The HS model controlled for race/ethnicity. The STAR*D model contained controls for age (continuous), sex (0 = male; 1 = female); marital status (0 = married/cohabiting; 1 = never married; 2 = divorced, widowed, or separated); and five principle components for genetic ancestry/population stratification. The GSP model controlled for age (continuous), sex (0 = male; 1 = female), and four principle components for genetic ancestry/population stratification. Depressive symptoms were measured by 3 scales: CES-D (HS), HAM-D (STAR*D), POMS short form (GSP).</p

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