- Beitrag
- Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone…
Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.
- ORCID
- 0000-0002-8309-094X
- Zugehörigkeit
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. ateumer@uni-greifswald.de.
- Zugehörigkeit
- Erasmus MC Academic Center for Thyroid Diseases, Rotterdam, The Netherlands.
- Zugehörigkeit
- Erasmus MC Academic Center for Thyroid Diseases, Rotterdam, The Netherlands.
- Zugehörigkeit
- Department of Biometry, Epidemiology and Medical Bioinformatics, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
- Zugehörigkeit
- Erasmus MC Academic Center for Thyroid Diseases, Rotterdam, The Netherlands.
- Zugehörigkeit
- Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
- Zugehörigkeit
- Department of Biometry, Epidemiology and Medical Bioinformatics, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
- Zugehörigkeit
- Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
- ORCID
- 0000-0002-7464-3354
- Zugehörigkeit
- Steno Diabetes Center Copenhagen, Gentofte, Denmark.
- Zugehörigkeit
- Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
- ORCID
- 0000-0001-7704-6611
- Zugehörigkeit
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Zugehörigkeit
- McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Zugehörigkeit
- Department of Biostatistics, University of Washington, Seattle, WA, USA.
- ORCID
- 0000-0001-8968-8996
- Zugehörigkeit
- Department of Nutrition, Exercise, and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
- ORCID
- 0000-0003-0585-6206
- Zugehörigkeit
- Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
- ORCID
- 0000-0002-4915-2254
- Zugehörigkeit
- Pathwest Laboratory Medicine WA, Nedlands, WA, 6009, Australia.
- Zugehörigkeit
- Bimetra, Clinical Research Center Ghent, Ghent University Hospital, Ghent, Belgium.
- Zugehörigkeit
- Human Genetics Center, University of Texas Health Science Center, 1200 Pressler Street, Houston, TX, 77030, USA.
- Zugehörigkeit
- Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.
- Zugehörigkeit
- Department of Cardiology, Ghent University Hospital, Ghent, Belgium.
- Zugehörigkeit
- Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.
- Zugehörigkeit
- Department of Medicine and Surgery, University of Parma, University Hospital of Parma, Parma, Italy.
- Zugehörigkeit
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
- Zugehörigkeit
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato, Monserrato, Italy.
- Zugehörigkeit
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
- Zugehörigkeit
- Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
- Zugehörigkeit
- Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Erlangen, Germany.
- ORCID
- 0000-0001-6099-7066
- Zugehörigkeit
- Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
- Zugehörigkeit
- Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
- Zugehörigkeit
- Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
- Zugehörigkeit
- Department of Clinical Chemistry, Ghent University Hospital, Ghent, Belgium.
- Zugehörigkeit
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato, Monserrato, Italy.
- Zugehörigkeit
- Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
- Zugehörigkeit
- National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies, Framingham, MA, USA.
- Zugehörigkeit
- Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lubeck, Bolzano, Italy.
- Zugehörigkeit
- Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
- Zugehörigkeit
- Helmholtz Zentrum München, Institute of Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany.
- Zugehörigkeit
- Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lubeck, Bolzano, Italy.
- Zugehörigkeit
- Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lubeck, Bolzano, Italy.
- ORCID
- 0000-0001-5526-1070
- Zugehörigkeit
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Zugehörigkeit
- German Research Centre Division of Cancer Epidemiology, Heidelberg, Germany.
- Zugehörigkeit
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
- ORCID
- 0000-0001-8748-3831
- Zugehörigkeit
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Zugehörigkeit
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
- Zugehörigkeit
- Leiden University Medical Center, Geriatrics and Gerontology, Leiden, The Netherlands.
- Zugehörigkeit
- Vrije Universiteit Medisch Centrum, Amsterdam, The Netherlands.
- ORCID
- 0000-0001-6320-0411
- Zugehörigkeit
- Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lubeck, Bolzano, Italy.
- Zugehörigkeit
- Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
- Zugehörigkeit
- Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
- Zugehörigkeit
- Pathwest Laboratory Medicine WA, Nedlands, WA, 6009, Australia.
- ORCID
- 0000-0003-0372-8585
- Zugehörigkeit
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
- Zugehörigkeit
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
- Zugehörigkeit
- Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
- Zugehörigkeit
- Department of Biometry, Epidemiology and Medical Bioinformatics, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
- ORCID
- 0000-0002-3246-8359
- Zugehörigkeit
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
- Zugehörigkeit
- National Institute for Health and Welfare, Helsinki, Finland.
- ORCID
- 0000-0001-8748-5597
- Zugehörigkeit
- Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
- GND
- 1148758380
- Zugehörigkeit
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
- Zugehörigkeit
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
- Zugehörigkeit
- Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
- Zugehörigkeit
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
- ORCID
- 0000-0003-2229-1120
- Zugehörigkeit
- Department of Medical Genetics, Division of Genetic Epidemiology, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
- Zugehörigkeit
- Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
- ORCID
- 0000-0002-4310-5297
- Zugehörigkeit
- Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
- Zugehörigkeit
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
- ORCID
- 0000-0003-2331-2448
- Zugehörigkeit
- Department of Biostatistics, Boston University, Boston, MA, USA.
- ORCID
- 0000-0002-0544-7368
- Zugehörigkeit
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
- Zugehörigkeit
- Pathwest Laboratory Medicine WA, Nedlands, WA, 6009, Australia.
- ORCID
- 0000-0002-0994-0184
- Zugehörigkeit
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
- Zugehörigkeit
- Department of Medicine and Surgery, University of Parma, University Hospital of Parma, Parma, Italy.
- ORCID
- 0000-0003-4156-1464
- Zugehörigkeit
- Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lubeck, Bolzano, Italy.
- Zugehörigkeit
- Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
- Zugehörigkeit
- Institute for Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
- Zugehörigkeit
- Helmholtz Zentrum München, Institute of Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany.
- ORCID
- 0000-0001-7786-7081
- Zugehörigkeit
- Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
- Zugehörigkeit
- Department of Data Analysis and Mathematical Modelling, Ghent University, Ghent, Belgium.
- Zugehörigkeit
- Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
- Zugehörigkeit
- Institute for Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
- Zugehörigkeit
- Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
- ORCID
- 0000-0002-9603-0460
- Zugehörigkeit
- Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands.
- ORCID
- 0000-0001-5047-4077
- Zugehörigkeit
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
- ORCID
- 0000-0002-0311-8472
- Zugehörigkeit
- Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
- Zugehörigkeit
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato, Monserrato, Italy.
- Zugehörigkeit
- Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lubeck, Bolzano, Italy.
- ORCID
- 0000-0002-3321-3972
- Zugehörigkeit
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Zugehörigkeit
- Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
- Zugehörigkeit
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato, Monserrato, Italy.
- Zugehörigkeit
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands.
- Zugehörigkeit
- Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lubeck, Bolzano, Italy.
- Zugehörigkeit
- Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA, USA.
- ORCID
- 0000-0003-1459-413X
- Zugehörigkeit
- Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
- Zugehörigkeit
- Helmholtz Zentrum München, Institute of Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany.
- Zugehörigkeit
- Department of Psychology, University of Edinburgh, Edinburgh, UK.
- ORCID
- 0000-0002-3746-9086
- Zugehörigkeit
- Lady Davis Institute, Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.
- Zugehörigkeit
- Biobanking and Cardiovascular Epidemiology, Ghent University Hospital, Ghent, Belgium.
- Zugehörigkeit
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
- Zugehörigkeit
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
- Zugehörigkeit
- The Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
- Zugehörigkeit
- Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
- Zugehörigkeit
- Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
- Zugehörigkeit
- Department of Epidemiology, Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
- Zugehörigkeit
- Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
- ORCID
- 0000-0003-1095-3852
- Zugehörigkeit
- The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1HH, UK.
- Zugehörigkeit
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Zugehörigkeit
- The Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Campus, Lambeth Palace Road, London, SE1 7EH, UK.
- Zugehörigkeit
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
- Zugehörigkeit
- Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow, UK.
- Zugehörigkeit
- AZ Sint Jan Brugge, Brugge, Belgium.
- Zugehörigkeit
- Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lubeck, Bolzano, Italy.
- Zugehörigkeit
- Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
- Zugehörigkeit
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
- Zugehörigkeit
- Chair of Epidemiology, Ludwig-Maximilians-Universität München, at UNIKA-T Augsburg, Augsburg, Germany.
- Zugehörigkeit
- Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
- Zugehörigkeit
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
- Zugehörigkeit
- Erasmus MC Academic Center for Thyroid Diseases, Rotterdam, The Netherlands.
- Zugehörigkeit
- Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.
- Zugehörigkeit
- Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.
- Zugehörigkeit
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
- ORCID
- 0000-0002-3658-1375
- Zugehörigkeit
- Department of Biostatistics, Boston University, Boston, MA, USA.
- Zugehörigkeit
- Diseases & Population (DaP) Geninfo Lab, School of Life Sciences, Westlake University and Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China.
- Zugehörigkeit
- Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
- Zugehörigkeit
- Erasmus MC Academic Center for Thyroid Diseases, Rotterdam, The Netherlands.
- Zugehörigkeit
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato, Monserrato, Italy.
- Zugehörigkeit
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
- Zugehörigkeit
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato, Monserrato, Italy.
- ORCID
- 0000-0002-4671-3714
- Zugehörigkeit
- Department of Biometry, Epidemiology and Medical Bioinformatics, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
- Zugehörigkeit
- Erasmus MC Academic Center for Thyroid Diseases, Rotterdam, The Netherlands.
- Zugehörigkeit
- Erasmus MC Academic Center for Thyroid Diseases, Rotterdam, The Netherlands.
Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets.
Vorschau
Einordnung
- Erschienen in:
-
Nature Communications
Vol. 9, H. 4455 - Band:
- 9
- Heft:
- 4455
- Datum der Veröffentlichung:
- 26.10.2018
- Sonstiger Identifikator (pubmed):
- 30367059
- DOI:
- 10.1038/s41467-018-06356-1
- Sprache:
- Englisch
- Ressourcentyp
: - Text
- DDC-Sachgruppe der DNB:
- 570 Biowissenschaften, Biologie
- Link URL:
- https://www.nature.com/articles/s41467-018-06356-1
- Link URL:
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203810/
- Einrichtung:
- Friedrich-Loeffler-Institut, Institut für Epidemiologie
- Physischer Standort:
- SD/2018/428
Zitieren
Zitier-Link kopieren
DOI (10.1038/s41467-018-06356-1)