Evidence of a causal relationship between genetic tendency to gain muscle mass and uterine leiomyomata
Sliz, E.; Tyrmi, J. S.; Rahmioglu, N.; Zondervan, K. T.; Becker, C. M.; FinnGen, ; Uimari, O.; Kettunen, J.
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Uterine leiomyomata (UL) are the most common benign tumours of the female genital tract with an estimated lifetime incidence of up to 70%1. To date, 7 genome-wide association studies (GWASs) have identified 35 loci predisposing to UL. To improve the understanding of the underlying genetic pathways, we conducted the largest genetic association study of UL to date in 426,558 European women from FinnGen and a previously published UL meta-GWAS2. We identified 36 novel and replicated 31 previously reported loci. Annotations of the potential candidate genes suggest involvement of smooth muscle cell (SMC) differentiation and/or proliferation-regulating genes in modulating UL risk. Our results further advocate that genetic predisposition to increased fat-free mass may be causally related to UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings provide novel insights into genetic risk factors related to UL, which may aid in developing novel treatment strategies.
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