PMC

Manhattan plot of the exome-array single-variant meta-analysis results including all endometriosis cases. Red line indicates our exome-wide significance threshold (P = 8.5 × 10^–7) and the orange line represents the threshold for suggestive association (P = 1 × 10^–4). SNP rs1801232 (red font) on chromosome 10 achieved our exome-wide significance threshold. Two other SNPs rs6542095 and rs13394619 (light orange font) on chromosome 2 also showed strong, albeit not exome-wide significant, association in the exome-array meta-analysis of discovery cohorts. These two SNPs represent the previously identified GWA association signals at IL1A and GREB1, respectively and of these rs13394619 achieved genome-wide significance in total association analysis including all cases from both the discovery and the replication cohorts.

Evidence of association with all endometriosis from the total association analysis across the 2p25.1 (GREB1) region. SNPs are shown as circles, triangles or squares, and different shapes denote the different categories of the SNPs: up-triangle for frameshift or splice SNPs, down-triangle for nonsynonymous SNPs, square for coding or untranslated region (UTR) SNPs; star for SNPs in tfbscons region (in a conserved region predicted to be a transcription factor binding site), square filled with ‘X’ symbol for SNPs located in mcs44placental region (in a region highly conserved in placental mammals) and circle for SNPs with no annotation information. The lead SNP at each known GWA risk locus reported by Nyholt et al., if present in our exome-array single-variant meta-analysis, is represented by a purple triangle. All other SNPs are color coded according to the strength of LD with the top genotyped SNP (as measured by r ² in the European 1000 Genomes data).