Refereed journal article or data article (A1)

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




List of AuthorsEeva Sliz, Jaakko S. Tyrmi, Nilufer Rahmioglu, Krina T. Zondervan, Christian M. Becker; FinnGen, Outi Uimari & Johannes Kettunen

PublisherNature Research

Publication year2023

JournalNature Communications

Journal name in sourceNature Communications

Volume number14

Issue number1

DOIhttp://dx.doi.org/10.1038/s41467-023-35974-7

URLhttps://www.nature.com/articles/s41467-023-35974-7

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/178924033


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.


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Last updated on 2023-24-03 at 15:43