Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis

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Gallagher, CS, Makinen, N, Harris, HR, Rahmioglu, N, Uimari, O, Cook, JP, Shigesi, N, Ferreira, T, Velez-Edwards, DR, Edwards, TL et al (show 49 more authors) , Mortlock, S, Ruhioglu, Z, Day, F, Becker, CM, Karhunen, V, Martikainen, H, Jarvelin, M-R, Cantor, RM, Ridker, PM, Terry, KL, Buring, JE, Gordon, SD, Medland, SE, Montgomery, GW, Nyholt, DR, Hinds, DA, Tung, JY, Perry, JRB, Lind, PA, Painter, JN, Martin, NG, Morris, AP, Chasman, DI, Missmer, SA, Zondervan, KT, Morton, CC, Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K, Bryc, Katarzyna, Elson, Sarah L, Fontanillas, Pierre, Furlotte, Nicholas A, Huber, Karen E, Kleinman, Aaron, Litterman, Nadia K, McIntyre, Matthew H, Mountain, Joanna L, Noblin, Elizabeth S, Northover, Carrie AM, Pitts, Steven J, Sathirapongsasuti, J Fah, Sazonova, Olga V, Shelton, Janie F, Shringarpure, Suyash, Tian, Chao, Vacic, Vladimir and Wilson, Catherine H (2019) Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis. NATURE COMMUNICATIONS, 10 (1). 4857-.

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	23andMe Research Team, Humans, Leiomyoma, Uterine Neoplasms, Endometriosis, Menorrhagia, Telomerase, Proportional Hazards Models, Signal Transduction, Polymorphism, Single Nucleotide, Adult, Middle Aged, Female, Receptor, Fibroblast Growth Factor, Type 4, Genome-Wide Association Study, Mendelian Randomization Analysis, Ataxia Telangiectasia Mutated Proteins, Forkhead Box Protein O1, White People
Depositing User:	Symplectic Admin
Date Deposited:	17 Feb 2020 09:41
Last Modified:	18 Feb 2023 03:28
DOI:	10.1038/s41467-019-12536-4
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3074702