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Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.
Sterenborg, Rosalie B T M; Steinbrenner, Inga; Li, Yong; Bujnis, Melissa N; Naito, Tatsuhiko; Marouli, Eirini; Galesloot, Tessel E; Babajide, Oladapo; Andreasen, Laura; Astrup, Arne; Åsvold, Bjørn Olav; Bandinelli, Stefania; Beekman, Marian; Beilby, John P; Bork-Jensen, Jette; Boutin, Thibaud; Brody, Jennifer A; Brown, Suzanne J; Brumpton, Ben; Campbell, Purdey J; Cappola, Anne R; Ceresini, Graziano; Chaker, Layal; Chasman, Daniel I; Concas, Maria Pina; Coutinho de Almeida, Rodrigo; Cross, Simone M; Cucca, Francesco; Deary, Ian J; Kjaergaard, Alisa Devedzic; Echouffo Tcheugui, Justin B; Ellervik, Christina; Eriksson, Johan G; Ferrucci, Luigi; Freudenberg, Jan; Fuchsberger, Christian; Gieger, Christian; Giulianini, Franco; Gögele, Martin; Graham, Sarah E; Grarup, Niels; Gunjaca, Ivana; Hansen, Torben; Harding, Barbara N; Harris, Sarah E; Haunsø, Stig; Hayward, Caroline; Hui, Jennie; Ittermann, Till; Jukema, J Wouter.
Afiliación
  • Sterenborg RBTM; Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Steinbrenner I; Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Li Y; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.
  • Bujnis MN; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.
  • Naito T; The University of Utah, Salt Lake City, UT, USA.
  • Marouli E; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Galesloot TE; Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
  • Babajide O; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
  • Andreasen L; Digital Environment Research Institute, Queen Mary University of London, London, UK.
  • Astrup A; Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Åsvold BO; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
  • Bandinelli S; Laboratory for Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
  • Beekman M; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Beilby JP; Department of Obesity and Nutritional Sciences, The Novo Nordisk Foundation, Hellerup, Denmark.
  • Bork-Jensen J; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  • Boutin T; Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
  • Brody JA; Geriatric Unit, Azienda Sanitaria Toscana Centro, Florence, Italy.
  • Brown SJ; Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Brumpton B; School of Biomedical Sciences, The University of Western Australia, Perth, WA, 6009, Australia.
  • Campbell PJ; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Cappola AR; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
  • Ceresini G; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Chaker L; Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.
  • Chasman DI; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  • Concas MP; HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, 7600, Norway.
  • Coutinho de Almeida R; Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.
  • Cross SM; Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania, Philadelphia, PA, USA.
  • Cucca F; Oncological Endocrinology, University of Parma, Parma, Italy.
  • Deary IJ; Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
  • Kjaergaard AD; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Echouffo Tcheugui JB; Department of Epidemiology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
  • Ellervik C; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Eriksson JG; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, USA.
  • Ferrucci L; Harvard Medical School, Boston, USA.
  • Freudenberg J; Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy.
  • Fuchsberger C; Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, 09042, Monserrato (CA), Italy.
  • Gieger C; Università di Sassari, Dipartimento di Scienze Biomediche, V.le San Pietro, 07100, Sassari (SS), Italy.
  • Giulianini F; Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, EH8 9JZ, Edinburgh, United Kingdom.
  • Gögele M; Steno Diabetes Center Aarhus, Aarhus University Hospital, Palle Juul-Jensens Blvd. 11, Entrance A, 8200, Aarhus, Denmark.
  • Graham SE; Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
  • Grarup N; Harvard Medical School, Boston, USA.
  • Gunjaca I; Faculty of Medical Science, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
  • Hansen T; Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Harding BN; Department of Clinical Biochemistry, Zealand University Hospital, Køge, Denmark.
  • Harris SE; Department of General Practice and Primary health Care, University of Helsinki, Helsinki, Finland.
  • Haunsø S; National University Singapore, Yong Loo Lin School of Medicine, Department of Obstetrics and Gynecology, Singapore, Singapore.
  • Hayward C; Longitudinal Study Section, National Institute on Aging, Baltimore, MD, USA.
  • Hui J; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
Nat Commun ; 15(1): 888, 2024 Jan 30.
Article en En | MEDLINE | ID: mdl-38291025
ABSTRACT
To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Glándula Tiroides / Tiroxina Tipo de estudio: Clinical_trials / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos
Texto completo
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Glándula Tiroides / Tiroxina Tipo de estudio: Clinical_trials / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos