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

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http://hdl.handle.net/10138/260553

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Valimaki , N , Kuisma , H , Pasanen , A , Heikinheimo , O , Sjoberg , J , Butzow , R , Sarvilinna , N , Heinonen , H-R , Tolvanen , J , Bramante , S , Tanskanen , T , Auvinen , J , Uimari , O , Alkodsi , A , Lehtonen , R , Kaasinen , E , Palin , K & Aaltonen , L A 2018 , ' Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability ' , eLife , vol. 7 , 37110 . https://doi.org/10.7554/eLife.37110

Title: Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability
Author: Valimaki, Niko; Kuisma, Heli; Pasanen, Annukka; Heikinheimo, Oskari; Sjoberg, Jari; Butzow, Ralf; Sarvilinna, Nanna; Heinonen, Hanna-Riikka; Tolvanen, Jaana; Bramante, Simona; Tanskanen, Tomas; Auvinen, Juha; Uimari, Outi; Alkodsi, Amjad; Lehtonen, Rainer; Kaasinen, Eevi; Palin, Kimmo; Aaltonen, Lauri A.
Contributor organization: Research Programs Unit
Genome-Scale Biology (GSB) Research Program
Department of Medical and Clinical Genetics
Medicum
Department of Pathology
Clinicum
Doctoral Programme in Clinical Research
Department of Obstetrics and Gynecology
Department of Biochemistry and Developmental Biology
Doctoral Programme in Integrative Life Science
Lauri Antti Aaltonen / Principal Investigator
HUS Gynecology and Obstetrics
Date: 2018-09-18
Language: eng
Number of pages: 50
Belongs to series: eLife
ISSN: 2050-084X
DOI: https://doi.org/10.7554/eLife.37110
URI: http://hdl.handle.net/10138/260553
Abstract: 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.
Subject: RENAL-CELL CANCER
TELOMERE LENGTH
EUROPEAN AMERICANS
GERMLINE MUTATIONS
TNRC6B ASSOCIATE
WIDE ASSOCIATION
HUMAN-DISEASE
RISK
SUSCEPTIBILITY
FIBROIDS
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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