Repository logo
 

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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Gallagher, CS 
Mäkinen, N 
Harris, HR 
Rahmioglu, N 

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.

Description

Keywords

Adult, Ataxia Telangiectasia Mutated Proteins, Endometriosis, Female, Forkhead Box Protein O1, Genome-Wide Association Study, Humans, Leiomyoma, Mendelian Randomization Analysis, Menorrhagia, Middle Aged, Polymorphism, Single Nucleotide, Proportional Hazards Models, Receptor, Fibroblast Growth Factor, Type 4, Signal Transduction, Telomerase, Uterine Neoplasms, White People

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

10

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_UU_12015/2)
This study was supported by the U.S. National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) grant HD060530 to C.C.M. C.C.M. is also supported by the NIHR Manchester Biomedical Research Centre. N.M. acknowledges support from the Academy of Finland (295693) and Orion Research Foundation. H.R.H. is supported by NIH K22 CA193860. T.F. is supported by the NIHR Biomedical Research Centre, Oxford. S.E.M. is supported by the National Health and Medical Research Council (NHMRC) Fellowship Scheme (1103623).