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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hans M Albertsen, Rakesh Chettier, Pamela Farrington, Kenneth Ward
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/88e6b2fab591422f8ff6c313e7319944
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:88e6b2fab591422f8ff6c313e7319944
record_format	dspace
spelling	oai:doaj.org-article:88e6b2fab591422f8ff6c313e73199442021-11-18T07:54:50ZGenome-wide association study link novel loci to endometriosis.1932-620310.1371/journal.pone.0058257https://doaj.org/article/88e6b2fab591422f8ff6c313e73199442013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23472165/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Endometriosis 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.Hans M AlbertsenRakesh ChettierPamela FarringtonKenneth WardPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58257 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hans M Albertsen Rakesh Chettier Pamela Farrington Kenneth Ward Genome-wide association study link novel loci to endometriosis.
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.
format	article
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
title	Genome-wide association study link novel loci to endometriosis.
title_short	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_sort	genome-wide association study link novel loci to endometriosis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/88e6b2fab591422f8ff6c313e7319944
work_keys_str_mv	AT hansmalbertsen genomewideassociationstudylinknovellocitoendometriosis AT rakeshchettier genomewideassociationstudylinknovellocitoendometriosis AT pamelafarrington genomewideassociationstudylinknovellocitoendometriosis AT kennethward genomewideassociationstudylinknovellocitoendometriosis
_version_	1718422788972216320

Genome-wide association study link novel loci to endometriosis.

Ejemplares similares