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

Sapkota, Yadav, Steinthorsdottir, Valgerdur, Morris, Andrew P., Fassbender, Amelie, Rahmioglu, Nilufer, De Vivo, Immaculata, Buring, Julie E., Zhang, Futao, Edwards, Todd L., Jones, Sarah, Dorien, O., Peterse, Danielle, 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, Edwards, Digna R. Velez, 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. and Nyholt, Dale R. (2017) Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism. Nature Communications, 8 15539-15539. doi:10.1038/ncomms15539


Author Sapkota, Yadav
Steinthorsdottir, Valgerdur
Morris, Andrew P.
Fassbender, Amelie
Rahmioglu, Nilufer
De Vivo, Immaculata
Buring, Julie E.
Zhang, Futao
Edwards, Todd L.
Jones, Sarah
Dorien, O.
Peterse, Danielle
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
Edwards, Digna R. Velez
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.
Title Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2017-05-24
Year available 2017
Sub-type Article (original research)
DOI 10.1038/ncomms15539
Open Access Status DOI
Volume 8
Start page 15539
End page 15539
Total pages 12
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1600 Chemistry
1300 Biochemistry, Genetics and Molecular Biology
3100 Physics and Astronomy
Abstract 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.
Formatted abstract
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.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Grant ID 241,944
WT084766/Z/08/Z
076113
R102-A9118
613674
FT0991022
631096
WT098017
MR/K011480/1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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