Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

Affiliations

• ¹ Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands.
• ² Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
• ³ Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.
• ⁴ The University of Utah, Salt Lake City, UT, USA.
• ⁵ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
• ⁶ Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
• ⁷ William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
• ⁸ Digital Environment Research Institute, Queen Mary University of London, London, UK.
• ⁹ Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
• ¹⁰ Laboratory for Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
• ¹¹ Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
• ¹² Department of Obesity and Nutritional Sciences, The Novo Nordisk Foundation, Hellerup, Denmark.
• ¹³ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
• ¹⁴ Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
• ¹⁵ Geriatric Unit, Azienda Sanitaria Toscana Centro, Florence, Italy.
• ¹⁶ Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
• ¹⁷ School of Biomedical Sciences, The University of Western Australia, Perth, WA, 6009, Australia.
• ¹⁸ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
• ¹⁹ MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
• ²⁰ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
• ²¹ Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.
• ²² HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, 7600, Norway.
• ²³ Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania, Philadelphia, PA, USA.
• ²⁴ Oncological Endocrinology, University of Parma, Parma, Italy.
• ²⁵ Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
• ²⁶ Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
• ²⁷ Department of Epidemiology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
• ²⁸ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
• ²⁹ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, USA.
• ³⁰ Harvard Medical School, Boston, USA.
• ³¹ Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy.
• ³² QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
• ³³ Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, 09042, Monserrato (CA), Italy.
• ³⁴ Università di Sassari, Dipartimento di Scienze Biomediche, V.le San Pietro, 07100, Sassari (SS), Italy.
• ³⁵ Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, EH8 9JZ, Edinburgh, United Kingdom.
• ³⁶ Steno Diabetes Center Aarhus, Aarhus University Hospital, Palle Juul-Jensens Blvd. 11, Entrance A, 8200, Aarhus, Denmark.
• ³⁷ Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
• ³⁸ Faculty of Medical Science, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
• ³⁹ Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.
• ⁴⁰ Department of Clinical Biochemistry, Zealand University Hospital, Køge, Denmark.
• ⁴¹ Department of General Practice and Primary health Care, University of Helsinki, Helsinki, Finland.
• ⁴² National University Singapore, Yong Loo Lin School of Medicine, Department of Obstetrics and Gynecology, Singapore, Singapore.
• ⁴³ Longitudinal Study Section, National Institute on Aging, Baltimore, MD, USA.
• ⁴⁴ Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
• ⁴⁵ Institute for Biomedicine (affiliated with the University of Lübeck), Eurac Research, Bolzano, Italy.
• ⁴⁶ Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
• ⁴⁷ Department of Internal Medicine, Cardiology, University of Michigan, Ann Arbor, MI, 48109, USA.
• ⁴⁸ Department of Medical Biology, University of Split, School of Medicine, Split, Croatia.
• ⁴⁹ Barcelona Institute for Global Health, Barcelona, Spain.
• ⁵⁰ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
• ⁵¹ Pathwest Laboratory Medicine WA, Nedlands, WA, 6009, Australia.
• ⁵² School of Population and Global Health, The University of Western Australia, Crawley, WA, 6009, Australia.
• ⁵³ Institute for Community Medicine, University Medicine Greifswald, 17475, Greifswald, Germany.
• ⁵⁴ DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
• ⁵⁵ Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
• ⁵⁶ Netherlands Heart Institute, Utrecht, the Netherlands.
• ⁵⁷ Finnish Institute for Health and Welfare, Population Health Unit, Helsinki and Oulu, Oulu, Finland.
• ⁵⁸ Clinical Medicine Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
• ⁵⁹ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
• ⁶⁰ Center of Physiological Research, University of California San Francisco, San Francisco, USA.
• ⁶¹ Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
• ⁶² Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
• ⁶³ Departments of Rheumatology and Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
• ⁶⁴ Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
• ⁶⁵ MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, UK.
• ⁶⁶ Computational Medicine, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
• ⁶⁷ Precision Healthcare University Research Institute, Queen Mary University of London, London, UK.
• ⁶⁸ Department of Endocrinology, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium.
• ⁶⁹ NHS Tayside, Scotland, Dundee, UK.
• ⁷⁰ Department of Biostatistics, Boston University, Boston, MA, USA.
• ⁷¹ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
• ⁷² Institute for Human Genetics, Technical University of Munich, Munich, Germany.
• ⁷³ University of Maryland School of Medicine, Division of Endocrinology, Diabetes and Nutrition, Baltimore, USA.
• ⁷⁴ Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD, 21201, USA.
• ⁷⁵ Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
• ⁷⁶ Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
• ⁷⁷ Department of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
• ⁷⁸ Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
• ⁷⁹ Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), Osaka University, Suita, Japan.
• ⁸⁰ Division of Population Health Genomics, School of Medicine, University of Dundee, DD19SY, Dundee, UK.
• ⁸¹ Center for Clinical Metabolic Research, Herlev-Gentofte University Hospital, Copenhagen, Denmark.
• ⁸² Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
• ⁸³ Chair of Epidemiology, Institute for Medical Information Processing, Biometry and Epidemiology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany.
• ⁸⁴ Department of Public Health, University of Split, School of Medicine, Split, Croatia.
• ⁸⁵ Algebra University College, Zagreb, Croatia.
• ⁸⁶ Departments of Epidemiology and Health Systems and Population Health, University of Washington, Seattle, WA, USA.
• ⁸⁷ Department of Nuclear Medicine, University Hospital Split, Split, Croatia.
• ⁸⁸ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
• ⁸⁹ Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, H3T 1E2, Canada.
• ⁹⁰ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, United Kingdom.
• ⁹¹ Department of Medicine IV - Nephrology and Primary Care, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.
• ⁹² Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
• ⁹³ Department of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
• ⁹⁴ The Department of Twin Research & Genetic Epidemiology, King's College London, St Thomas' Campus, Lambeth Palace Road, London, SE1 7EH, UK.
• ⁹⁵ Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
• ⁹⁶ Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
• ⁹⁷ Leiden Computational Biology Center, Leiden University Medical Center, Leiden, The Netherlands.
• ⁹⁸ Department of Pattern Recognition and Bioinformatics, Delft University of Technology, Delft, The Netherlands.
• ⁹⁹ Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
• ¹⁰⁰ Medical School, The University of Western Australia, Crawley, WA, 6009, Australia.
• ¹⁰¹ Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
• ¹⁰² Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
• ¹⁰³ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
• ¹⁰⁴ Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
• ¹⁰⁵ Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.
• ¹⁰⁶ Department of Psychiatry, University of Michigan, Ann Arbor, MI, 48109, USA.
• ¹⁰⁷ CIBSS - Centre for Integrative Biological Signalling Studies, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
• ¹⁰⁸ Institute for Community Medicine, University Medicine Greifswald, 17475, Greifswald, Germany. [email protected].
• ¹⁰⁹ DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany. [email protected].
• ¹¹⁰ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. [email protected].
• ¹¹¹ Department of Population Medicine and Lifestyle Diseases Prevention, Medical University of Bialystok, Bialystok, Poland. [email protected].
• ¹¹² Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands. [email protected].
• ¹¹³ Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. [email protected].