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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata

Author

Listed:
  • Eeva Sliz

    (University of Oulu
    Biocenter Oulu)

  • Jaakko S. Tyrmi

    (University of Oulu
    Biocenter Oulu)

  • Nilufer Rahmioglu

    (University of Oxford
    University of Oxford)

  • Krina T. Zondervan

    (University of Oxford
    University of Oxford)

  • Christian M. Becker

    (University of Oxford)

  • Outi Uimari

    (Oulu University Hospital
    University of Oulu and Oulu University Hospital
    University of Oulu and Oulu University Hospital)

  • Johannes Kettunen

    (University of Oulu
    Biocenter Oulu)

Abstract

Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1 A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35974-7
    DOI: 10.1038/s41467-023-35974-7
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