Identification of susceptibility genes for peritoneal, ovarian, and deep infiltrating endometriosis using a pooled sample-based genome-wide association study.

Content Provider	Europe PMC
Author	Borghese, Bruno Tost, Jörg de Surville, Magalie Busato, Florence Letourneur, Frank Mondon, Françoise Vaiman, Daniel Chapron, Charles
Copyright Year	2015
Abstract	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.
ISSN	23146133
Journal	Biomed Research International
Volume Number	2015
PubMed Central reference number	PMC4334615
PubMed reference number	25722978
e-ISSN	23146141
DOI	10.1155/2015/461024
Language	English
Publisher	Hindawi
Publisher Date	2015-02-04
Access Restriction	Open
Rights License	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. Copyright © 2015 Bruno Borghese et al.
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology