Boxplot of methylation values for the 7 CpGs in <i>INS</i> promoter with respect to SNPs other than rs689 in T1D patients.

<p>Methylation at CpGs -69, −102, −180 and −206 are associated with rs3842748. More distant SNPs showed a much weaker correlation with methylation at CpG -69 and -102 for rs4320932 and with methylation at CpGs -102, -135, -180 and −206 for rs6356. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036278#pone.0036278.s001" target="_blank">Figure S1</a> for SNP locations. P-values are calculated by Krukal-Wallis test.</p

CpG methylation in the <i>INS</i> promoter in T2D patients and controls.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036278#s2" target="_blank">Results</a> are expressed as mean ± sd. <i>P</i>-values are calculated by Wilcoxon rank sum test.</p

Lack of correlation between age and <i>INS</i> promoter methylation in T1D patients (green) and Controls (red).

<p>Only CpG -180 methylation showed a slight downward trend with age (r = 0.09, p = 0.01). The figure also shows the distribution of individual methylation values, and the differences between T1D and control subjects for CpGs -19, -135, -180, and -234.</p

Heatmap analysis of the relationship between DNA methylation of the whole proximal <i>INS</i> promoter and disease status.

<p>Each row represents one individual.</p

Correlation matrix of the methylation values (%) at the <i>INS</i> promoter CpG sites in T1D patients (R in bold, p-value below).

<p>The T1D-associated hypomethylated CpGs -19, -135 and -234 are highly correlated (<10⁻¹⁶).</p

UCSC Genome Browser map of the <i>INS</i> locus : localization of genes, CpG islands (CGI), variants and CpG sites.

<p>Genes are represented by blue boxes (exons) and lines (intron). Under genes, CGI are in green. Green intensity and size of the box is function of the size and the number of CpG included in CGI. Polymorphisms are represented by black boxes, under CGI. Below, a zoom of the <i>INS</i> promoter allowing the localization and representation of the isolated CpG sites, according to the TSS, represented by the red arrow.</p

Main characteristics of T1D patients and age-matched non diabetic controls.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036278#s2" target="_blank">Results</a> are expressed as mean ± sd.</p

Association of haplotypes derived from rs2856650, rs3740689 and rs10769258 with VT risk in two GWAS.

<p>The meta-analysis of the AGT haplotype-associated ORs obtained in the two GWAS samples lead to an overall OR of 2.78 [2.01–3.81] (p = 4.72 10⁻¹⁰). In a combined analysis of the individual-level genotype data of the two GWAS, the AGT haplotype frequency was estimated to 0.054 and 0.019 in cases and controls, respectively. This led to a combined OR of 3.03 [2.23–4.10] (p = 8.96 10⁻¹³) compared to the most frequent GGT haplotype (with estimated frequency 0.330 and 0.343 in cases and controls, respectively).</p

Pairwise linkage disequilibrium r² between genotyped SNPs at the 11p11.2 locus over the 47,373,425–48,064,194 bp region in the second GWAS study (Germain et al. Plos One 2011).

<p>Pairwise linkage disequilibrium r² between genotyped SNPs at the 11p11.2 locus over the 47,373,425–48,064,194 bp region in the second GWAS study (Germain et al. Plos One 2011).</p

Pairwise linkage disequilibrium r² between genotyped SNPs mapping from <i>F2</i> to <i>PTPRJ</i> genes at the 11p11.2 locus in a sample of 1,542 VT cases.

<p>Pairwise linkage disequilibrium r² between genotyped SNPs mapping from <i>F2</i> to <i>PTPRJ</i> genes at the 11p11.2 locus in a sample of 1,542 VT cases.</p