Háskólinn í ReykjavíkReykjavik UniversityHáskóli ÍslandsUniversity of IcelandRafnar, ThorunnBjarni GunnarssonÓlafur A. Stefánssonsulem, patrickIngason, AndrésFrigge, Michael L.Lilja StefánsdóttirJón K. SigurðssonTragante, ViniciusSteinthorsdottir, ValgerdurStyrkarsdottir, UnnurStacey, Simon N.Gudmundsson, JuliusArnadottir, GudnyOddsson, AsmundurZink, FlorianHalldorsson, GisliSveinbjornsson, GardarKristjansson, RagnarÓlafur B. DavíðssonAnna Þórhildur SalvarsdóttirÁsgeir ThoroddsenElísabet A. HelgadottirKatrín KristjánsdóttirOrri IngþórssonValur GuðmundssonGeirsson, Reynir T.Ragnheiður ÁrnadottirGudbjartsson, DanielMásson, GísliAsselbergs, Folkert W.Jón Gunnlaugur JónassonKarl ÓlafssonThorsteinsdottir, UnnurHalldórsson, BjarniThorleifsson, GudmarStefansson, Kari2019-11-012019-11-012018-09-07Rafnar, T., Gunnarsson, B., Stefansson, O.A. et al. Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits. Nat Commun 9, 3636 (2018) doi:10.1038/s41467-018-05428-62041-1723 (eISSN)https://hdl.handle.net/20.500.11815/1328We thank the individuals who participated in the study and whose contribution made this work possible. We acknowledge the Icelandic Cancer Registry for assistance in the ascertainment of the cancer patients. T.R., B.G., P.S., B.V.H., G.T, and K.S. designed the study and interpreted the results. A.S, A.T., E.A.H., K.K., O.I., V.G., R.T.G., R.A., J.G.J., and K.O. carried out the subject ascertainment, recruitment, and collection of clinical data. U.S., V.S., S.N.S., J.G., G.A.A., A.O., F.Z., G.H., R.P.K., O.B.D., G.M., V.T., F.W.A., and U.T. collected, processed, and analyzed the genotype and phenotype data. O.A.S. performed the functional annotations. A.I., M.L.F., L.S., J.K.S., G.S., D.F.G., B.G., and B.V.H., performed the statistical and bioinformatics analyses. T.R., B.G., O.A.S, G.T., and K.S., drafted the manuscript. All authors contributed to the final version of the paper.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.3636eninfo:eu-repo/semantics/openAccessGenome associationChronic lymphocytic leukemiaEpithelial ovarian cancerBone mineral densitySusceptibility lociBreast cancerRisk lociSequence variantsTelomere lengthIdentifies 2GenamengiHvítblæðiEitlarKrabbameinEggjastokkarBeinþéttniSteinefniBrjóstakrabbameinKrabbameinsrannsóknirinfo:eu-repo/semantics/articleNature Communications10.1038/s41467-018-05428-6