SYNPLOT [38] for a section of the intergenic region (NCBI Build 37: 87,140,000bp to 87,190,000bp) ~94kb upstream of <i>NTRK2</i> on chromosome 9q21.33.
<p>Since regulatory elements are usually found with conserved regions of the genome, we interrogated the region of our top hits using this <i>in silico</i> analysis to look for conserved regions across multiple species. The multiple alignments of (top to bottom) human, cow and mouse sequences were performed across the complete intergenic region <i>SLC28A3</i> to <i>NTRK2</i> using LAGAN. The segment of the alignments shown here is the region that contains the top association hits (<i>P</i><5×10<sup>-6</sup>). The central plotted curves show the degree of conservation of sequence across all three species, on a vertical scale 0–1 (= 100%), such that the peaks represent CNS. CNS are defined here as regions with a nucleotide sequence conservation level of ≥0.7, i.e. ≥ to the least conserved exon sequence in the two genes (not shown on this plot) <i>SLC28A3</i> and <i>NTRK2</i> flanking the intergenic region of interest. Blue boxes indicate repetitive sequence in all 3 species. The human sequence is also annotated with positions of: (i) LINE-1 elements (yellow); (ii) the top genotyped SNPs (red vertical bars) including the top SNP rs1086204, and the SNP of interest rs1866439; (iii) the top imputed SNPs (blue vertical bars) including the top SNP rs1140653; (iv) the CpG island-like element identified using CpG Island Seacher (green); and (v) positions of peaks of mono-methylation of lysine 4 of histone H3 (H3K4Me1) as measured in NHEK or NHLF cell lines (mauve) or in H1-hESC human embryonic stem cells (orange) by the ENCODE project, as identified using the UCSC browser (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119333#pone.0119333.s009" target="_blank">S9 Fig</a>.).</p
