University of Oulu

Välimäki, N., Kuisma, H., Pasanen, A., Heikinheimo, O., Sjöberg, J., Bützow, R., Sarvilinna, N., Heinonen, H., Tolvanen, J., Bramante, S., Tanskanen, T., Auvinen, J., Uimari, O., Alkodsi, A., Lehtonen, R., Kaasinen, E., Palin, K., Aaltonen, L. (2018) Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability. eLife, 7, e37110. doi:10.7554/eLife.37110

Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability

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Author: Välimäki, Niko1,2; Kuisma, Heli1,2; Pasanen, Annukka3;
Organizations: 1Department of Medical and Clinical Genetics, University of Helsinki
2Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki
3Department of Pathology, University of Helsinki and Helsinki University Hospital
4Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital
5Institute of Biomedicine, Biochemistry and Developmental Biology, University of Helsinki
6Northern Finland Birth Cohorts’ Project Center, Faculty of Medicine, University of Oulu
7Center for Life Course Health Research, Faculty of Medicine, University of Oulu
8Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center Oulu, Oulu University Hospital, University of Oulu
9Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 6.3 MB)
Persistent link:
Language: English
Published: eLife Sciences Publications, 2018
Publish Date: 2018-12-10


Uterine leiomyomas (ULs) are benign tumors that are a major burden to women’s health. A genome-wide association study on 15,453 UL cases and 392,628 controls was performed, followed by replication of the genomic risk in six cohorts. Effects of the risk alleles were evaluated in view of molecular and clinical characteristics. 22 loci displayed a genome-wide significant association. The likely predisposition genes could be grouped to two biological processes. Genes involved in genome stability were represented by TERT, TERC, OBFC1 — highlighting the role of telomere maintenance — TP53 and ATM. Genes involved in genitourinary development, WNT4, WT1, SALL1, MED12, ESR1, GREB1, FOXO1, DMRT1 and uterine stem cell marker antigen CD44, formed another strong subgroup. The combined risk contributed by the 22 loci was associated with MED12 mutation-positive tumors. The findings link genes for uterine development and genetic stability to leiomyomagenesis, and in part explain the more frequent occurrence of UL in women of African origin.

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Series: eLife
ISSN: 2050-084X
ISSN-E: 2050-084X
ISSN-L: 2050-084X
Volume: 7
Article number: e37110
DOI: 10.7554/eLife.37110.001
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3122 Cancers
3123 Gynaecology and paediatrics
Funding: The study was supported by grants from Academy of Finland (Finnish Center of Excellence Program 2012 – 2017, 2018 – 2025, No. 1250345 and 312041), European Research Council (ERC, 695727), Cancer Society of Finland, Sigrid Juselius Foundation and Jane and Aatos Erkko Foundation. NV received a grant from the Academy of Finland (No. 287665). KP received a grant from Nordic Information for Action eScience Center (NIASC), the Nordic Center of Excellence financed by NordForsk (No. 62721). This research has been conducted using the UK Biobank Resource, project #32506.
Academy of Finland Grant Number: 250345
Detailed Information: 250345 (Academy of Finland Funding decision)
312041 (Academy of Finland Funding decision)
287665 (Academy of Finland Funding decision)
Dataset Reference: Supplementary files:
Copyright information: Copyright Välimäki et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.