Genome-wide association study link novel loci to endometriosis.

Endometriosis is a common gynecological condition with complex etiology defined by the presence of endometrial glands and stroma outside the womb. Endometriosis is a common cause of both cyclic and chronic pelvic pain, reduced fertility, and reduced quality-of-life. Diagnosis and treatment of endome...

Full description

Bibliographic Details
Main Authors: Hans M Albertsen, Rakesh Chettier, Pamela Farrington, Kenneth Ward
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23472165/pdf/?tool=EBI
_version_ 1818701300195393536
author Hans M Albertsen
Rakesh Chettier
Pamela Farrington
Kenneth Ward
author_facet Hans M Albertsen
Rakesh Chettier
Pamela Farrington
Kenneth Ward
author_sort Hans M Albertsen
collection DOAJ
description Endometriosis is a common gynecological condition with complex etiology defined by the presence of endometrial glands and stroma outside the womb. Endometriosis is a common cause of both cyclic and chronic pelvic pain, reduced fertility, and reduced quality-of-life. Diagnosis and treatment of endometriosis is, on average, delayed by 7-10 years from the onset of symptoms. Absence of a timely and non-invasive diagnostic tool is presently the greatest barrier to the identification and treatment of endometriosis. Twin and family studies have documented an increased relative risk in families. To identify genetic factors that contribute to endometriosis we conducted a two-stage genome-wide association study (GWAS) of a European cohort including 2,019 surgically confirmed endometriosis cases and 14,471 controls. Three of the SNPs we identify associated at P<5×10(-8) in our combined analysis belong to two loci: LINC00339-WNT4 on 1p36.12 (rs2235529; P = 8.65×10(-9), OR = 1.29, CI = 1.18-1.40) and RND3-RBM43 on 2q23.3 (rs1519761; P = 4.70×10(-8), OR = 1.20, Cl = 1.13-1.29, and rs6757804; P = 4.05×10(-8), OR = 1.20, Cl = 1.13-1.29). Using an adjusted Bonferoni significance threshold of 4.51×10(-7) we identify two additional loci in our meta-analysis that associate with endometriosis:, RNF144B-ID4 on 6p22.3 (rs6907340; P = 2.19×10(-7), OR = 1.20, Cl = 1.12-1.28), and HNRNPA3P1-LOC100130539 on 10q11.21 (rs10508881; P = 4.08×10(-7), OR = 1.19, Cl = 1.11-1.27). Consistent with previously suggested associations to WNT4 our study implicate a 150 kb region around WNT4 that also include LINC00339 and CDC42. A univariate analysis of documented infertility, age at menarche, and family history did not show allelic association with these SNP markers. Clinical data from patients in our study reveal an average delay in diagnosis of 8.4 years and confirm a strong correlation between endometriosis severity and infertility (n = 1182, P<0.001, OR = 2.18). This GWAS of endometriosis was conducted with high diagnostic certainty in cases, and with stringent handling of population substructure. Our findings broaden the understanding of the genetic factors that play a role in endometriosis.
first_indexed 2024-12-17T15:18:39Z
format Article
id doaj.art-88e6b2fab591422f8ff6c313e7319944
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-17T15:18:39Z
publishDate 2013-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-88e6b2fab591422f8ff6c313e73199442022-12-21T21:43:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5825710.1371/journal.pone.0058257Genome-wide association study link novel loci to endometriosis.Hans M AlbertsenRakesh ChettierPamela FarringtonKenneth WardEndometriosis is a common gynecological condition with complex etiology defined by the presence of endometrial glands and stroma outside the womb. Endometriosis is a common cause of both cyclic and chronic pelvic pain, reduced fertility, and reduced quality-of-life. Diagnosis and treatment of endometriosis is, on average, delayed by 7-10 years from the onset of symptoms. Absence of a timely and non-invasive diagnostic tool is presently the greatest barrier to the identification and treatment of endometriosis. Twin and family studies have documented an increased relative risk in families. To identify genetic factors that contribute to endometriosis we conducted a two-stage genome-wide association study (GWAS) of a European cohort including 2,019 surgically confirmed endometriosis cases and 14,471 controls. Three of the SNPs we identify associated at P<5×10(-8) in our combined analysis belong to two loci: LINC00339-WNT4 on 1p36.12 (rs2235529; P = 8.65×10(-9), OR = 1.29, CI = 1.18-1.40) and RND3-RBM43 on 2q23.3 (rs1519761; P = 4.70×10(-8), OR = 1.20, Cl = 1.13-1.29, and rs6757804; P = 4.05×10(-8), OR = 1.20, Cl = 1.13-1.29). Using an adjusted Bonferoni significance threshold of 4.51×10(-7) we identify two additional loci in our meta-analysis that associate with endometriosis:, RNF144B-ID4 on 6p22.3 (rs6907340; P = 2.19×10(-7), OR = 1.20, Cl = 1.12-1.28), and HNRNPA3P1-LOC100130539 on 10q11.21 (rs10508881; P = 4.08×10(-7), OR = 1.19, Cl = 1.11-1.27). Consistent with previously suggested associations to WNT4 our study implicate a 150 kb region around WNT4 that also include LINC00339 and CDC42. A univariate analysis of documented infertility, age at menarche, and family history did not show allelic association with these SNP markers. Clinical data from patients in our study reveal an average delay in diagnosis of 8.4 years and confirm a strong correlation between endometriosis severity and infertility (n = 1182, P<0.001, OR = 2.18). This GWAS of endometriosis was conducted with high diagnostic certainty in cases, and with stringent handling of population substructure. Our findings broaden the understanding of the genetic factors that play a role in endometriosis.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23472165/pdf/?tool=EBI
spellingShingle Hans M Albertsen
Rakesh Chettier
Pamela Farrington
Kenneth Ward
Genome-wide association study link novel loci to endometriosis.
PLoS ONE
title Genome-wide association study link novel loci to endometriosis.
title_full Genome-wide association study link novel loci to endometriosis.
title_fullStr Genome-wide association study link novel loci to endometriosis.
title_full_unstemmed Genome-wide association study link novel loci to endometriosis.
title_short Genome-wide association study link novel loci to endometriosis.
title_sort genome wide association study link novel loci to endometriosis
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23472165/pdf/?tool=EBI
work_keys_str_mv AT hansmalbertsen genomewideassociationstudylinknovellocitoendometriosis
AT rakeshchettier genomewideassociationstudylinknovellocitoendometriosis
AT pamelafarrington genomewideassociationstudylinknovellocitoendometriosis
AT kennethward genomewideassociationstudylinknovellocitoendometriosis