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Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis.
Gallagher, C S; Mäkinen, N; Harris, H R; Rahmioglu, N; Uimari, O; Cook, J P; Shigesi, N; Ferreira, T; Velez-Edwards, D R; Edwards, T L; Mortlock, S; Ruhioglu, Z; Day, F; Becker, C M; Karhunen, V; Martikainen, H; Järvelin, M-R; Cantor, R M; Ridker, P M; Terry, K L; Buring, J E; Gordon, S D; Medland, S E; Montgomery, G W; Nyholt, D R; Hinds, D A; Tung, J Y; Perry, J R B; Lind, P A; Painter, J N; Martin, N G; Morris, A P; Chasman, D I; Missmer, S A; Zondervan, K T; Morton, C C.
Afiliación
  • Gallagher CS; Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
  • Mäkinen N; Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. netta_makinen@dfci.harvard.edu.
  • Harris HR; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
  • Rahmioglu N; Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
  • Uimari O; Endometriosis CaRe Centre, Nuffield Department of Women's and Reproductive Health, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
  • Cook JP; Department of Obstetrics and Gynecology, Oulu University Hospital and PEDEGO Research Unit & Medical Research Center Oulu, University of Oulu and Oulu University Hospital, 90220, Oulu, Finland.
  • Shigesi N; Department of Biostatistics, University of Liverpool, Liverpool, L69 3GL, UK.
  • Ferreira T; Endometriosis CaRe Centre, Nuffield Department of Women's and Reproductive Health, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
  • Velez-Edwards DR; Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
  • Edwards TL; Big Data Institute, Li Ka Shing Center for Health Information and Discovery, Oxford University, Oxford, OX3 7LF, UK.
  • Mortlock S; Vanderbilt Genetics Institute, Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN, 37203, USA.
  • Ruhioglu Z; Division of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, 37203, USA.
  • Day F; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, 4072, Australia.
  • Becker CM; Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Karhunen V; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Martikainen H; Endometriosis CaRe Centre, Nuffield Department of Women's and Reproductive Health, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
  • Järvelin MR; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, 90220, Oulu, Finland.
  • Cantor RM; Unit of Primary Health Care, Oulu University Hospital, 90220, Oulu, Finland.
  • Ridker PM; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, W2 1PG, UK.
  • Terry KL; Department of Obstetrics and Gynecology, Oulu University Hospital and PEDEGO Research Unit & Medical Research Center Oulu, University of Oulu and Oulu University Hospital, 90220, Oulu, Finland.
  • Buring JE; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, 90220, Oulu, Finland.
  • Gordon SD; Unit of Primary Health Care, Oulu University Hospital, 90220, Oulu, Finland.
  • Medland SE; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, W2 1PG, UK.
  • Montgomery GW; Biocenter Oulu, University of Oulu, 90220, Oulu, Finland.
  • Nyholt DR; Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, Middlesex, UB8 3PH, UK.
  • Hinds DA; Department of Human Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Tung JY; Division of Preventative Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Perry JRB; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
  • Lind PA; Division of Preventative Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Painter JN; Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Martin NG; Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Morris AP; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, 4072, Australia.
  • Chasman DI; Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Missmer SA; Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
  • Zondervan KT; Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, QLD, 4059, Australia.
  • Morton CC; 23andMe, Mountain View, CA, 94041, USA.
Nat Commun ; 10(1): 4857, 2019 10 24.
Article en En | MEDLINE | ID: mdl-31649266
Uterine leiomyomata (UL) are the most common neoplasms of the female reproductive tract and primary cause for hysterectomy, leading to considerable morbidity and high economic burden. Here we conduct a GWAS meta-analysis in 35,474 cases and 267,505 female controls of European ancestry, identifying eight novel genome-wide significant (P < 5 × 10-8) loci, in addition to confirming 21 previously reported loci, including multiple independent signals at 10 loci. Phenotypic stratification of UL by heavy menstrual bleeding in 3409 cases and 199,171 female controls reveals genome-wide significant associations at three of the 29 UL loci: 5p15.33 (TERT), 5q35.2 (FGFR4) and 11q22.3 (ATM). Four loci identified in the meta-analysis are also associated with endometriosis risk; an epidemiological meta-analysis across 402,868 women suggests at least a doubling of risk for UL diagnosis among those with a history of endometriosis. These findings increase our understanding of genetic contribution and biology underlying UL development, and suggest overlapping genetic origins with endometriosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Uterinas / Endometriosis / Leiomioma Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Adult / Female / Humans / Middle aged Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Uterinas / Endometriosis / Leiomioma Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Adult / Female / Humans / Middle aged Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido