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

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

Effects of disrupted <i>GRB10</i> through knock-down on islet function.

<p>(A) Disrupted <i>GRB10</i> in INS-1 rat β-cells markedly reduced glucose-stimulated insulin secretion. (B) <i>GRB10</i> knock-down showed reduced glucose-stimulated insulin secretion at 20 mM glucose and glucagon secretion at 1 mM glucose in human pancreatic islets (N_insulin = 7, N_glucagon = 6 donors of human pancreatic islets; 3–6 measurements in each experiment for each donor). (C) <i>GRB10</i> knock-down resulted in a reduction of insulin and glucagon mRNA expression (N = 3 donors of human pancreatic islets; 3 measurements in each experiment for each donor). * <i>p</i><0.05; ** <i>p</i><0.01, *** <i>p</i><0.001. Error bars denote SEM.</p

Parent-of-origin effect of <i>GRB10</i> rs933360 on insulin secretion and glucose levels.

<p>(A) No significant effect for CIR was observed from the paternally transmitted A-allele. (B) Carriers of the maternally transmitted A-allele showed lower CIR compared to the G-allele. (C) Carriers of the paternally transmitted A-allele had elevated fasting plasma glucose levels, whereas (D) the maternally transmitted A-allele was associated with lower fasting plasma glucose levels. Fin-Swe = Trios from Finland and Sweden, Amish = Amish Family Diabetes Study, Kuopio = Kuopio Offspring Study.</p

Genes of biological interest within 500 kb of lead SNPs associated with WC_adjBMI or WHR_adjBMI.

<p>Genes of biological interest within 500 kb of lead SNPs associated with WC_adjBMI or WHR_adjBMI.</p

Forty-four WHR_adjBMI loci showing significant sex-differences.

<p>Chr: Chromosome; Pos: position; EAF: Effect Allele Frequency; EA: Effect allele; OA: Other allele</p><p>^a ‘Yes’ if the locus is mentioned as WHR_adjBMI locus for the first time</p><p>^b ‘Yes’ if the sex-difference in the effect on WHR_adjBMI is reported for the first time</p><p>^c Effect allele is according to the WHR_adjBMI increasing allele according to the associated sex.</p><p>The table shows the sex-specific (age-group combined) results, ordered by largest, positive effect in women to largest, negative effect in women. The age- and sex-specific results (four strata), more detailed information on the loci and on the screens for which they were detected are given in <b><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005378#pgen.1005378.s021" target="_blank">S5 Table</a></b>.</p