Meta-analysis of genetic association between two HLA SNPs and knee OA.

<p>Forest plot of study-specific estimates and random-effects summary effect size and 95% confidence intervals (95%CIs) for the genetic association with knee OA of (<b>A</b>) the major allele (T) at rs7775228 in three published studies and the deCODE case-control study (<b>B</b>) the major allele (C) at rs10947262 in three published studies and seven additional European studies. Square sizes are proportional to the number of cases in each study.</p

Map of the HLA class II region in harboring markers rs7775228 and rs10947262.

<p>The frequency of haplotype DRB1*1502 DQA1*0103 DQB1*0601 and its linkage disequilibrium with rs7775228 and rs10947262 in three ethnic groups is shown.</p

Characteristics of cases and controls of unpublished studies included in the analysis.

<p>MAF =  minor allele frequency.</p><p>(1) <b>Minor allele = C, major allele = T.</b></p><p>(2) <b>Minor allele = T, major allele = C.</b></p

Regional association plot for the locus of rs2862851 rs12206662/rs10948155.

<p>SNPs are plotted by position in a 800-kb window versus association with mJSW (−log10 P) for A. rs2862851 (TGFA locus) and B. rs12206662/rs10948155 (SUPT3H/RUNX2 locus). The purple dot highlights the most significant SNP in discovery analysis. Blue peaks indicate recombination rates. The SNPs surrounding the most significant SNP are color coded to reflect their LD with this SNP (from pairwise r² values from the HapMap CEU). Genes, exons and the direction of transcription from the University of California at Santa Cruz genome browser are depicted. Plots were generated using Locus Zoom [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006260#pgen.1006260.ref009" target="_blank">9</a>]</p

mJSW and OA associated variants are co-localized with potential gene regulatory markers.

<p>We examined the epigenetic histone marks in Chondrogenic cells, osteoblasts, hMSC, K562, HUVEC, HeLA and NHEK cells. This heatmap of the percentage of variants in gene regulatory regions (enhancer/promoter associated regions) in high LD (r² >0.8) with lead GWAS SNP. Enrichment was calculated according [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006260#pgen.1006260.ref025" target="_blank">25</a>].</p

Manhattan plot for association of mJSW in the discovery phase.

<p>The -log10 P values, for each of the 2.5 million tests performed as part of the genome wide association of minimal joint space width of the hip (mJSW), plotted against their position per chromosome. Full results of the discovery GWAS are accessible through <a href="http://www.glimdna.org" target="_blank">www.glimdna.org</a>. The gray solid horizontal line corresponds to the genome-wide significant threshold (P = 5x10-8). The dotted grey line corresponds to the selection for replication threshold (P = 1x10^-5).</p

Association of mJSW loci with previously reported phenotypes

<p>Association of mJSW loci with previously reported phenotypes</p

Association between protein coding variants identified by exome-sequencing and mJSW.

<p>Association between protein coding variants identified by exome-sequencing and mJSW.</p

Association of mJSW loci with Hip OA

<p>Association of mJSW loci with Hip OA</p

Results from the minimal Joint Space Width genome-wide association study; discovery, replication and joint meta-analysis

<p>Results from the minimal Joint Space Width genome-wide association study; discovery, replication and joint meta-analysis</p