Research Article Identification of Susceptibility Genes for Peritoneal, Ovarian, and Deep Infiltrating Endometriosis Using a Pooled Sample-Based Genome-Wide Association Study

Copyright © 2015 Bruno Borghese et al.This is an open access article distributed under theCreative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Characterizing genetic contributions to endometriosis might help to shorten the time to diagnosis, especially in the most severe forms, but represents a challenge. Previous genome-wide association studies (GWAS) made no distinction between peritoneal endometriosis (SUP), endometrioma (OMA), and deep infiltrating endometriosis (DIE).We therefore conducted a pooled sample-based GWAS and distinguished histologically confirmed endometriosis subtypes. We performed an initial discovery step on 10-individual pools (two pools per condition). After quality control filtering, aMonte-Carlo simulationwas used to rank the significant SNPs according to the ratio of allele frequencies and the coefficient of variation. Then, a replication step of individual genotyping was conducted in an independent cohort of 259 cases and 288 controls. Our approachwas very stringent but probablymissed a lot of information due to theMonte-Carlo simulation, which likely explained why we did not replicate results from “classic ” GWAS. Four variants (rs227849, rs4703908, rs2479037, and rs966674) were significantly associated with an increased risk of OMA. Rs4703908,