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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.

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