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

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.

Genome-wide characterization of circulating metabolic biomarkers

“…Less well-characterized relationships included a positive association between genetically predicted lactate levels and benign neoplasm of uterus. This potentially causal association is concordant with a recent GWAS that linked genetic tendency to gain muscle mass with uterine fibroids 51 . We also found an inverse association between genetically predicted circulating glycine levels and blood pressure, which is supported by a strong observational association with hypertension 52 and by genetic data 53 .…”