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Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits

Author

Listed:
  • Thorunn Rafnar

    (deCODE Genetics/Amgen)

  • Bjarni Gunnarsson

    (deCODE Genetics/Amgen)

  • Olafur A. Stefansson

    (deCODE Genetics/Amgen)

  • Patrick Sulem

    (deCODE Genetics/Amgen)

  • Andres Ingason

    (deCODE Genetics/Amgen)

  • Michael L. Frigge

    (deCODE Genetics/Amgen)

  • Lilja Stefansdottir

    (deCODE Genetics/Amgen)

  • Jon K. Sigurdsson

    (deCODE Genetics/Amgen)

  • Vinicius Tragante

    (deCODE Genetics/Amgen
    University of Utrecht)

  • Valgerdur Steinthorsdottir

    (deCODE Genetics/Amgen)

  • Unnur Styrkarsdottir

    (deCODE Genetics/Amgen)

  • Simon N. Stacey

    (deCODE Genetics/Amgen)

  • Julius Gudmundsson

    (deCODE Genetics/Amgen)

  • Gudny A. Arnadottir

    (deCODE Genetics/Amgen)

  • Asmundur Oddsson

    (deCODE Genetics/Amgen)

  • Florian Zink

    (deCODE Genetics/Amgen)

  • Gisli Halldorsson

    (deCODE Genetics/Amgen)

  • Gardar Sveinbjornsson

    (deCODE Genetics/Amgen)

  • Ragnar P. Kristjansson

    (deCODE Genetics/Amgen)

  • Olafur B. Davidsson

    (deCODE Genetics/Amgen)

  • Anna Salvarsdottir

    (Landspitali University Hospital)

  • Asgeir Thoroddsen

    (Landspitali University Hospital)

  • Elisabet A. Helgadottir

    (Landspitali University Hospital)

  • Katrin Kristjansdottir

    (Landspitali University Hospital)

  • Orri Ingthorsson

    (Akureyri Hospital)

  • Valur Gudmundsson

    (Akureyri Hospital)

  • Reynir T. Geirsson

    (Landspitali University Hospital
    University of Iceland)

  • Ragnheidur Arnadottir

    (Landspitali University Hospital)

  • Daniel F. Gudbjartsson

    (deCODE Genetics/Amgen
    University of Iceland)

  • Gisli Masson

    (deCODE Genetics/Amgen)

  • Folkert W. Asselbergs

    (University of Utrecht
    Netherlands Heart Institute
    University College London
    University College London)

  • Jon G. Jonasson

    (University of Iceland
    Landspitali University Hospital)

  • Karl Olafsson

    (Landspitali University Hospital)

  • Unnur Thorsteinsdottir

    (deCODE Genetics/Amgen
    University of Iceland)

  • Bjarni V. Halldorsson

    (deCODE Genetics/Amgen
    Reykjavik University)

  • Gudmar Thorleifsson

    (deCODE Genetics/Amgen)

  • Kari Stefansson

    (deCODE Genetics/Amgen
    University of Iceland)

Abstract

Uterine leiomyomas are common benign tumors of the myometrium. We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women (16,595 cases and 523,330 controls), uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36.12 (CDC42/WNT4), 2p25.1 (GREB1), 20p12.3 (MCM8), and 6q26.2 (SYNE1/ESR1). Polygenic score for leiomyoma, computed using UKB data, is significantly correlated with risk of cancer in the Icelandic population. Functional annotation suggests that the non-coding risk variants affect multiple genes, including ESR1. Our results provide insights into the genetic background of leiomyoma that are shared by other benign and malignant tumors and highlight the role of hormones in leiomyoma growth.

Suggested Citation

  • Thorunn Rafnar & Bjarni Gunnarsson & Olafur A. Stefansson & Patrick Sulem & Andres Ingason & Michael L. Frigge & Lilja Stefansdottir & Jon K. Sigurdsson & Vinicius Tragante & Valgerdur Steinthorsdotti, 2018. "Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05428-6
    DOI: 10.1038/s41467-018-05428-6
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    Cited by:

    1. Mihaela Pavličev & Caitlin E. McDonough-Goldstein & Andreja Moset Zupan & Lisa Muglia & Yueh-Chiang Hu & Fansheng Kong & Nagendra Monangi & Gülay Dagdas & Nina Zupančič & Jamie Maziarz & Debora Sinner, 2024. "A common allele increases endometrial Wnt4 expression, with antagonistic implications for pregnancy, reproductive cancers, and endometriosis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Kadir Buyukcelebi & Alexander J. Duval & Fatih Abdula & Hoda Elkafas & Fidan Seker-Polat & Mazhar Adli, 2024. "Integrating leiomyoma genetics, epigenomics, and single-cell transcriptomics reveals causal genetic variants, genes, and cell types," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Eeva Sliz & Jaakko S. Tyrmi & Nilufer Rahmioglu & Krina T. Zondervan & Christian M. Becker & Outi Uimari & Johannes Kettunen, 2023. "Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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