Figure 2: Regional association plot for the 9q22.23 PTCH1 locus, potential functional elements and genotype-dependent expression.

(a) Regional association plot for the 9q22.23 PTCH1 locus. P values (−log10) of SNP association with spine BMD in the Icelandic discovery samples are plotted against their positions at the 9q22.23 locus. SNPs are coloured to reflect their linkage disequilibrium (LD) with rs28377268 in the data set. The red line indicates recombination rates, based on the Icelandic recombination map for males and females combined⁴⁷, with the peaks indicating recombination hotspots defining LD blocks in Icelanders. Known genes in the region are shown underneath the plot, taken from the UCSC genes track in the UCSC Genome Browser. All positions are in NCBI Build 36 coordinates. The plot was created using a stand-alone version of LocusZoom software⁴⁸. (b) Functional annotation of potential functional elements in the region. Transcription factor binding sites and DNase hypersensitive areas from the ENCODE data is shown^43,44 and enhancer and promoter states from the Roadmap consortium²⁶. Location of rs28377268 is indicated by a green vertical line. (c) Genotype-dependent gene expression or the PTCH1 gene in blood samples. The P value is derived from regression of the MLR on the carrier status of rs28377268, adjusting for age and sex, and differential cell counts.