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Get Free AccessAbstract Uterine leiomyomata (UL) are the most common neoplasms of the female reproductive tract and primary cause for hysterectomy, leading to considerable morbidity and high economic burden. Here we conduct a GWAS meta-analysis in 35,474 cases and 267,505 female controls of European ancestry, identifying eight novel genome-wide significant ( P < 5 × 10 −8 ) loci, in addition to confirming 21 previously reported loci, including multiple independent signals at 10 loci. Phenotypic stratification of UL by heavy menstrual bleeding in 3409 cases and 199,171 female controls reveals genome-wide significant associations at three of the 29 UL loci: 5p15.33 ( TERT ), 5q35.2 ( FGFR4 ) and 11q22.3 ( ATM ). Four loci identified in the meta-analysis are also associated with endometriosis risk; an epidemiological meta-analysis across 402,868 women suggests at least a doubling of risk for UL diagnosis among those with a history of endometriosis. These findings increase our understanding of genetic contribution and biology underlying UL development, and suggest overlapping genetic origins with endometriosis.
C. Scott Gallagher, Netta Mäkinen, Holly R. Harris, Nilüfer Rahmioğlu, Outi Uimari, James P. Cook, Nina Shigesi, Teresa Ferreira, Digna Velez-Edwards, Todd L. Edwards, Sally Mortlock, Z. Ruhioglu, Felix R. Day, Christian M. Becker, Ville Karhunen, Hannu Martikainen, Paul M Ridker, Rita M. Cantor, Paul M. Ridker, Kathryn L. Terry, Julie E. Buring, Scott D. Gordon, Sarah E. Medland, Grant W. Montgomery, Dale R. Nyholt, David A. Hinds, Joyce Y. Tung, Michelle Agee, Babak Alipanahi, Adam Auton, Robert K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas, Nicholas A. Furlotte, Karen E. Huber, Aaron Kleinman, Nadia K. Litterman, Matthew H. McIntyre, Joanna L. Mountain, Elizabeth S. Noblin, Carrie A. M. Northover, Steven J. Pitts, J. Fah Sathirapongsasuti, Olga V. Sazonova, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Vladimir Vacic, Catherine H. Wilson, John R. B. Perry, Penelope A. Lind, Jodie N. Painter, Nicholas G. Martin, Andrew P. Morris, Daniel I. Chasman, Stacey A. Missmer, Krina T. Zondervan, Cynthia C. Morton (2019). Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis. , 10(1), DOI: https://doi.org/10.1038/s41467-019-12536-4.
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Type
Article
Year
2019
Authors
59
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1038/s41467-019-12536-4
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