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

Yadav Sapkota(St. Jude Children's Research Hospital), Valgerður Steinthórsdóttir(deCODE Genetics (Iceland)), Andrew P. Morris(Centre for Human Genetics), Amelie Fassbender(Leuven Institute for Fertility and Embryology), Nilüfer Rahmioğlu(Centre for Human Genetics), Immaculata De Vivo(Brigham and Women's Hospital), Julie E. Buring(Brigham and Women's Hospital), Futao Zhang(The University of Queensland), Todd L. Edwards(Vanderbilt University Medical Center), Sarah Jones(Vanderbilt Health), O Dorien(Leuven Institute for Fertility and Embryology), Daniëlle Peterse(Leuven Institute for Fertility and Embryology), Kathryn M. Rexrode(Brigham and Women's Hospital), Paul M. Ridker(Brigham and Women's Hospital), Andrew J. Schork(Sankt Hans Hospital), Stuart MacGregor(QIMR Berghofer Medical Research Institute), Nicholas G. Martin(QIMR Berghofer Medical Research Institute), Christian M. Becker(John Radcliffe Hospital), Sosuke Adachi(Niigata University), Kosuke Yoshihara(Niigata University), Takayuki Enomoto(Niigata University), Atsushi Takahashi(RIKEN Center for Integrative Medical Sciences), Yoichiro Kamatani(RIKEN Center for Integrative Medical Sciences), Koichi Matsuda(Tokyo Medical University), Michiaki Kubo(RIKEN Center for Integrative Medical Sciences), Guðmar Þorleifsson(deCODE Genetics (Iceland)), Reynir Tómas Geirsson(Reykjavík University), Unnur Þorsteinsdóttir(deCODE Genetics (Iceland)), Leanne Wallace(The University of Queensland), iPSYCH-SSI-Broad Group(University of Copenhagen), Thomas Werge(Lundbeck Foundation), Wesley K. Thompson(The University of Queensland), Jian Yang(The University of Queensland), Digna R. Velez Edwards(Aarhus University), Mette Nyegaard(Aarhus University), Siew‐Kee Low(Centre for Human Genetics), Krina T. Zondervan(Brigham and Women's Hospital), Stacey A. Missmer(Brigham and Women's Hospital), Thomas D’Hooghe(Merck KGaA, Darmstadt (Germany)), Grant W. Montgomery(Brigham and Women's Hospital), Daniel I. Chasman(Brigham and Women's Hospital), Kari Stefansson(deCODE Genetics (Iceland)), Joyce Y. Tung(Queensland University of Technology), Dale R. Nyholt(Queensland University of Technology)
Nature Communications
May 24, 2017
10.1038/ncomms15539
Cited by 339Open Access
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Abstract

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.

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