Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism

Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometrio...

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Vydáno v:	Nature communications Ročník 8; číslo 1; s. 15539 - 12
Hlavní autoři:	Sapkota, Yadav, Steinthorsdottir, Valgerdur, Morris, Andrew P., Fassbender, Amelie, Rahmioglu, Nilufer, De Vivo, Immaculata, Buring, Julie E., Zhang, Futao, Edwards, Todd L., Jones, Sarah, O, Dorien, Peterse, Daniëlle, Rexrode, Kathryn M., Ridker, Paul M., Schork, Andrew J., MacGregor, Stuart, Martin, Nicholas G., Becker, Christian M., Adachi, Sosuke, Yoshihara, Kosuke, Enomoto, Takayuki, Takahashi, Atsushi, Kamatani, Yoichiro, Matsuda, Koichi, Kubo, Michiaki, Thorleifsson, Gudmar, Geirsson, Reynir T., Thorsteinsdottir, Unnur, Wallace, Leanne M., Yang, Jian, Velez Edwards, Digna R., Nyegaard, Mette, Low, Siew-Kee, Zondervan, Krina T., Missmer, Stacey A., D'Hooghe, Thomas, Montgomery, Grant W., Chasman, Daniel I., Stefansson, Kari, Tung, Joyce Y., Nyholt, Dale R.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 24.05.2017 Nature Publishing Group Nature Portfolio
Témata:	38/47 45/43 631/208/205/2138 631/208/457/649 692/308/2056 692/499 Adult Aged Endometriosis Endometriosis - genetics Endometriosis - metabolism Epidemiology Estrogen Receptor alpha - genetics Estrogen Receptor alpha - metabolism Female Fertility Genetic Loci - genetics Genetic Predisposition to Disease Genetics Genome-Wide Association Study Genomes Genotype Gonadal Steroid Hormones - metabolism Gynecology Health care Hospitals Humanities and Social Sciences Humans Meta-analysis Metabolic Networks and Pathways - genetics Metabolism Middle Aged multidisciplinary Obstetrics Polymorphism, Single Nucleotide Preventive medicine Public health R&D Research & development Science Science (multidisciplinary) Steroids United Kingdom > UK Queensland Australia United States > US Tennessee Japan California Iceland Nashville Tennessee Belgium Massachusetts Denmark Australia Aarhus Denmark
ISSN:	2041-1723, 2041-1723
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Shrnutí:	Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometriosis cases and 191,596 controls. In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk ( P <5 × 10 −8 ), implicating genes involved in sex steroid hormone pathways ( FN1 , CCDC170 , ESR1 , SYNE1 and FSHB ). Conditional analysis identified five secondary association signals, including two at the ESR1 locus, resulting in 19 independent single nucleotide polymorphisms (SNPs) robustly associated with endometriosis, which together explain up to 5.19% of variance in endometriosis. These results highlight novel variants in or near specific genes with important roles in sex steroid hormone signalling and function, and offer unique opportunities for more targeted functional research efforts. Endometriosis is a major cause of infertility. Molecular mechanisms underlying the disease involve genetic and environmental risk factors. In a meta-analysis of eleven GWA studies, Sapkota and colleagues identify five novel risk loci, implicating steroid sex hormone pathways in the pathogenesis.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally to this work. A full list of consortium members appears at the end of the paper.
ISSN:	2041-1723 2041-1723
DOI:	10.1038/ncomms15539