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

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dc.contributorHáskólinn í Reykjavíken_US
dc.contributorReykjavik Universityen_US
dc.contributorHáskóli Íslandsen_US
dc.contributorUniversity of Icelanden_US
dc.contributor.authorRafnar, Thorunn
dc.contributor.authorBjarni Gunnarsson
dc.contributor.authorÓlafur A. Stefánsson
dc.contributor.authorsulem, patrick
dc.contributor.authorIngason, Andrés
dc.contributor.authorFrigge, Michael L.
dc.contributor.authorLilja Stefánsdóttir
dc.contributor.authorJón K. Sigurðsson
dc.contributor.authorTragante, Vinicius
dc.contributor.authorSteinthorsdottir, Valgerdur
dc.contributor.authorStyrkarsdottir, Unnur
dc.contributor.authorStacey, Simon N.
dc.contributor.authorGudmundsson, Julius
dc.contributor.authorArnadottir, Gudny
dc.contributor.authorOddsson, Asmundur
dc.contributor.authorZink, Florian
dc.contributor.authorHalldorsson, Gisli
dc.contributor.authorSveinbjornsson, Gardar
dc.contributor.authorKristjansson, Ragnar
dc.contributor.authorÓlafur B. Davíðsson
dc.contributor.authorAnna Þórhildur Salvarsdóttir
dc.contributor.authorÁsgeir Thoroddsen
dc.contributor.authorElísabet A. Helgadottir
dc.contributor.authorKatrín Kristjánsdóttir
dc.contributor.authorOrri Ingþórsson
dc.contributor.authorValur Guðmundsson
dc.contributor.authorGeirsson, Reynir T.
dc.contributor.authorRagnheiður Árnadottir
dc.contributor.authorGudbjartsson, Daniel
dc.contributor.authorMásson, Gísli
dc.contributor.authorAsselbergs, Folkert W.
dc.contributor.authorJón Gunnlaugur Jónasson
dc.contributor.authorKarl Ólafsson
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorHalldórsson, Bjarni
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorStefansson, Kari
dc.contributor.departmentLæknadeild (HÍ)en_US
dc.contributor.departmentFaculty of Medicine (UI)en_US
dc.contributor.schoolSchool of Science and Engineering (RU)en_US
dc.contributor.schoolHeilbrigðisvísindasvið (HÍ)en_US
dc.contributor.schoolSchool of Health Sciences (UI)en_US
dc.contributor.schoolTækni- og verkfræðideild (HR)en_US
dc.contributor.schoolVerkfræði- og náttúruvísindasvið (HÍ)en_US
dc.contributor.schoolSchool of Engineering and Natural Sciences (UI)en_US
dc.date.accessioned2019-11-01T10:31:50Z
dc.date.available2019-11-01T10:31:50Z
dc.date.issued2018-09-07
dc.descriptionWe 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.en_US
dc.description.abstractUterine 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.en_US
dc.description.sponsorshipThis research has been conducted using the UK Biobank Resource under Application Number ‘24711’.en_US
dc.description.versionPeer revieweden_US
dc.format.extent3636en_US
dc.identifier.citationRafnar, 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/s41467-018-05428-6en_US
dc.identifier.doi10.1038/s41467-018-05428-6
dc.identifier.issn2041-1723 (eISSN)
dc.identifier.journalNature Communicationsen_US
dc.identifier.urihttps://hdl.handle.net/20.500.11815/1328
dc.language.isoenen_US
dc.publisherSpringer Science and Business Media LLCen_US
dc.relation.ispartofseriesNature Communications;9(1)
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectGenome associationen_US
dc.subjectChronic lymphocytic leukemiaen_US
dc.subjectEpithelial ovarian canceren_US
dc.subjectBone mineral densityen_US
dc.subjectSusceptibility locien_US
dc.subjectBreast canceren_US
dc.subjectRisk locien_US
dc.subjectSequence variantsen_US
dc.subjectTelomere lengthen_US
dc.subjectIdentifies 2en_US
dc.subjectGenamengien_US
dc.subjectHvítblæðien_US
dc.subjectEitlaren_US
dc.subjectKrabbameinen_US
dc.subjectEggjastokkaren_US
dc.subjectBeinþéttnien_US
dc.subjectSteinefnien_US
dc.subjectBrjóstakrabbameinen_US
dc.subjectKrabbameinsrannsókniren_US
dc.titleVariants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traitsen_US
dc.typeinfo:eu-repo/semantics/articleen_US
dcterms.licenseThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en_US

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