Association of HK1 with Glycated Hemoglobin Table 1. SNPs with a P-Value Lower than 1026 for Association with Adjusted Glycated Hemoglobin. 6.8E-10 1.2E-08 2.5E-07 1.7E-07 2.3E-08 2.8E-12 6.2E-12 9.8E-08 5.5E-08 6.4E-09 FDRe 7.8E-05 8.1E-04 7.8E-03 5.8E-03 1.3E-03 9.6E-07 1.1E-06 3.8E-03 2.7E-03 5.5E-04 SNP rs1402837 rs560887 rs563694 rs552976 rs6709087 rs730497 rs4607517 rs13266634 rs906216 rs7072268 Locus 2q24.3 2q24.3 2q24.3 2q24.3 2q24.3 7p13 7p13 8q24.11 10q21.3 10q21.3 aMAF: Minor Allele Frequency. bHW: Deviation from Hardy-Weinberg equilibrium P-value. cAll analyses were performed using adjusted glycated hemoglobin values (see text for details). dNSC: Non-Synonymous Coding SNP. eFDR: False Discovery Rate. doi:10.1371/journal.pgen.1000312.t001 Position (kb) Nearest Gene Function MAFa HWb Beta (%HbA1c)c P-Valuec 169466 169471 169482 169500 169507 44190 44202 118254 70768 70770 G6PC2 G6PC2 G6PC2 G6PC2 G6PC2 GCK GCK SLC30A8 HK1 HK1 - - - intron intron intron intron NSCd intron intron 0.23 0.29 0.34 0.35 0.23 0.17 0.17 0.30 0.44 0.50 0.87 0.88 0.76 0.97 0.68 0.82 0.67 0.50 0.15 0.10 0.023 20.020 20.017 20.018 0.021 0.030 0.029 20.019 20.017 0.018 Figure 1. Genetic Context of Significant Associations. Genomic context for each of four loci with significant association with glycated hemoglobin levels. (A) G6PC2 locus (2q24.3); (B) GCK locus (19p13.2); (C) SLC30A8 locus (8q24.11); (D) HK1 locus (10q21.3). Upper panel: Genes from RefSeq release 25. Only one isoform is shown when multiple splicing variants are known. Lower Panel: SNPs are shown according to their physical location and 2log10 P-values for association with glycated hemoglobin. At each locus, the SNP with the lowest P-value is represented by a black dot. The color of each other SNP was determined according to its linkage disequilibrium (r2) with the SNP with the lowest P-value, with colors varying from blue (r2 = 0) to red (r2 = 1). In Figure 1-D, the chromosomal position of rs2305198 is shown as this SNP was selected by the model selection algorithm in addition to the SNP with the lowest P-value (see text for details). The red line represents the genome-wide significance threshold of 561028. Also shown is the genetic distance in cM from the lowest P-value SNP (light grey line) along with the position of recombination hotspots (light grey vertical bars). Recombination rates and hotspots are based on HapMap data, as described by McVean et al.[46] and Winckler et al.[47]. doi:10.1371/journal.pgen.1000312.g001 PLoS Genetics | www.plosgenetics.org 4 December 2008 | Volume 4 | Issue 12 | e1000312