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BioMed Research International
Volume 2015, Article ID 461024, 8 pages
Research Article

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

1Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, CNRS (UMR 8104), 75014 Paris, France
2Inserm, U1016, 75014 Paris, France
3Université Paris Descartes, Sorbonne Paris Cité, Service de Gynécologie Obstétrique 2 et Médecine de la Reproduction, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, AP-HP, 74014 Paris, France
4Laboratoire Epigénétique et Environnement, Centre National de Génotypage, Institut de Génomique/CEA, 91000 Evry, France

Received 3 September 2014; Revised 17 December 2014; Accepted 15 January 2015

Academic Editor: Mariela Bilotas

Copyright © 2015 Bruno Borghese et al. This is an open access article distributed under the Creative Commons Attribution 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, a Monte-Carlo simulation was 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 approach was very stringent but probably missed a lot of information due to the Monte-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, located close to ZNF366, provided a higher risk of OMA (OR = 2.22; 95% CI: 1.26–3.92) and DIE, especially with bowel involvement (OR = 2.09; 95% CI: 1.12–3.91). ZNF366, involved in estrogen metabolism and progression of breast cancer, is a new biologically plausible candidate for endometriosis.