ArticleNature communications2020
GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer.
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Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 75 papers, 9 of them syntheses that pooled it.
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75citing papers in PubMed, 9 pooled it
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Who cites it
75 citing papers in PubMed, 9 syntheses or guidelines pooled it.
- Genetic drivers of etiologic heterogeneity in thyroid cancer.Nature communications · 2026Pooled it
- Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk.Nature genetics · 2026Pooled it
- Genome-wide association study and polygenic risk prediction of hypothyroidism.Nature genetics · 2025Pooled it
- Causal relationships between gut microbiota and hypothyroidism: a Mendelian randomization study.Endocrine · 2024Pooled it
- Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.Nature communications · 2024Pooled it
- Mendelian randomization study of thyroid function and anti-Müllerian hormone levels.Frontiers in endocrinology · 2023Pooled it
- Pooled it
- Systematic review of Mendelian randomization studies on risk of cancer.BMC medicine · 2022Pooled it
- Reference Intervals for Serum Thyroid-Stimulating Hormone Based on a Recent Nationwide Cross-Sectional Study and Meta-Analysis.Frontiers in endocrinology · 2021Pooled it
- Thyroid Stimulating Hormone Levels and Risk of Hospital-Acquired Acute Kidney Injury: A Nationwide Cohort Study.Kidney medicine · 2026Article
- An integrated multiomics-based risk model for predicting the prognosis and immune microenvironment status in patients with papillary thyroid carcinoma.Gland surgery · 2026Article
- Molecular Determinants of Thyroid Cancer Progression: Thyroid Hormone Signaling, the BRAF/MAPK Pathway, and Emerging miRNA Biomarkers.Biomedicines · 2026Review
- Dissecting pleiotropy to gain mechanistic insights into human disease.Nature reviews. Genetics · 2026Review
- The FOXE1 rs965513 polymorphism: a pleiotropic risk locus associated with thyroid function, BRAFScientific reports · 2026Article
- A genome-wide interaction study of thyroid-stimulating hormone levels and particulate matter exposure among Koreans.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2026Article
- Genetics of Thyroid Function: Relevance for Biology and Disease Management.The Journal of clinical endocrinology and metabolism · 2025Review
- Causal associations between thyroid function and sarcopenia-related traits: a Mendelian randomization study.Hormones (Athens, Greece) · 2025Article
- The role of cellular heterogeneity in thyroid cancer: a multi-modal analysis approach with Mendelian randomization.Discover oncology · 2025Article
- Cross-tissue transcriptome-wide analysis reveals novel insights into thyroid cancer etiology.Discover oncology · 2025Article
- Independent Effects of Hypothyroidism and Obesity on Endometrial Cancer Risk Revealed by Mendelian Randomisation.Biomedicines · 2025Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
56 authors.
Wei Zhou *Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. wzhou@broadinstitute.org.ORCID http://orcid.org/0000-0001-7719-0859
Ben Brumpton *K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.ORCID http://orcid.org/0000-0002-3058-1059
Omer Kabil *Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Julius Gudmundsson *deCODE genetics/AMGEN, 101, Reykjavik, Iceland.
Gudmar Thorleifsson *deCODE genetics/AMGEN, 101, Reykjavik, Iceland.
Josh WeinstockCenter for Statistical Genetics and Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.ORCID http://orcid.org/0000-0001-7013-1899
Matthew ZawistowskiCenter for Statistical Genetics and Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.ORCID http://orcid.org/0000-0002-3005-083X
Jonas B NielsenK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.ORCID http://orcid.org/0000-0002-6654-2852
Layal ChakerErasmus MC Academic Center for Thyroid Diseases, Rotterdam, The Netherlands.
Marco MediciErasmus MC Academic Center for Thyroid Diseases, Rotterdam, The Netherlands.
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-8309-094X
Silvia NaitzaIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato, Monserrato, Italy.
Serena SannaIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato, Monserrato, Italy.ORCID http://orcid.org/0000-0002-3768-1749
Ulla T SchultheissFaculty of Medicine and Medical Center, Institute of Genetic Epidemiology, University of Freiburg, Freiburg, Germany.
Anne CappolaDivision of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Juha KarjalainenAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
Mitja KurkiAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
Morgan OnekaDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.ORCID http://orcid.org/0000-0002-9672-0445
Peter TaylorThyroid Research Group, Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, UK.
Lars G FritscheCenter for Statistical Genetics and Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.ORCID http://orcid.org/0000-0002-2110-1690
Sarah E GrahamDepartment of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.ORCID http://orcid.org/0000-0003-1271-2489
Brooke N WolfordDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.ORCID http://orcid.org/0000-0003-3153-1552
William OvertonCenter for Statistical Genetics and Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
Humaira RasheedK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.ORCID http://orcid.org/0000-0002-3331-5864
Eirin B HaugK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Maiken E GabrielsenK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Anne Heidi SkogholtK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Ida SurakkaDepartment of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
George Davey SmithMedical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-1407-8314
Anita PanditCenter for Statistical Genetics and Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
Tanmoy RoychowdhuryDepartment of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Whitney E HornsbyDepartment of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Jon G JonassonLandspitali-University Hospital, 101, Reykjavik, Iceland.
Leigha SenterDivision of Human Genetics, Ohio State University Comprehensive Cancer Center, Columbus, Ohio, 43210, USA.
Sandya LiyanarachchiDepartment of Cancer Biology and Genetics, Ohio State University Comprehensive Cancer Center, Columbus, Ohio, 43210, USA.
Matthew D RingelDivision of Endocrinology, Diabetes, and Metabolism, The Ohio State University, Columbus, Ohio, 43210, USA.
Li XuDepartment of Head and Neck Surgery, and Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
Lambertus A KiemeneyRadboud University Medical Centre, Radboud Institute for Health Sciences, 6500HB, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0002-2368-1326
Huiling HeDepartment of Cancer Biology and Genetics, Ohio State University Comprehensive Cancer Center, Columbus, Ohio, 43210, USA.
Romana T Netea-MaierDivision of Endocrinology, Department of Internal Medicine, Radboud University Medical Centre, Radboud Institute for Molecular Life Sciences, 6500HB, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0002-9603-0460
Jose I MayordomoUniversity of Colorado Hospital, Aurora, Colorado, 80045, USA.
Theo S PlantingaDepartment of Pathology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, 6500HB, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0003-4990-6084
Jon HrafnkelssonLandspitali-University Hospital, 101, Reykjavik, Iceland.
Hannes HjartarsonLandspitali-University Hospital, 101, Reykjavik, Iceland.
Erich M SturgisDepartment of Head and Neck Surgery, and Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
Aarno PalotieAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
Mark DalyAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
Cintia E CitterioDivision of Metabolism Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.ORCID http://orcid.org/0000-0002-3547-5458
Peter ArvanDivision of Metabolism Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Chad M BrummettDivision of Pain Medicine, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Michael BoehnkeCenter for Statistical Genetics and Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.ORCID http://orcid.org/0000-0002-6442-7754
Albert de la ChapelleDepartment of Cancer Biology and Genetics, Ohio State University Comprehensive Cancer Center, Columbus, Ohio, 43210, USA.ORCID http://orcid.org/0000-0001-9345-9248
Kari StefanssondeCODE genetics/AMGEN, 101, Reykjavik, Iceland.ORCID http://orcid.org/0000-0003-1676-864X
Kristian HveemK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Cristen J WillerDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.ORCID http://orcid.org/0000-0001-5645-4966
Bjørn Olav ÅsvoldK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. bjorn.o.asvold@ntnu.no.ORCID http://orcid.org/0000-0003-3837-2101
Funding
Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3MRegional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3MUniversity of Michigan Training Program in Genomic ScienceT32HG000040 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sebastian Zoellner · 1995 to 2026
$16.4MIdentifying Genes for Type 2 Diabetes: FUSIONU01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2009 to 2021
$11.6MThe Ohio State University and MD Anderson Cancer Center Thyroid Cancer SPOREP50CA168505 · NCI · OHIO STATE UNIVERSITY · PI KIRSCHNER, LAWRENCE S · 2013 to 2017
$10.9MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MUsing genetics to discover mechanisms of myocardial infarctionR01HL109946 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI YUQING Eugene CHEN, Ida Liisa Surakka · 2011 to 2026
$8.9MTHYROCYTE PROTEIN TRANSPORT TO THE CELL SURFACER01DK040344 · NIDDK · YESHIVA UNIVERSITY · PI ARVAN, PETER · 1993 to 2018
$7.3MIdentifying Genes for Type 2 Diabetes:FUSIONR01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2003 to 2025
$6.7MUsing Genetics to Inform Mechanism of Cardiovascular DiseaseR35HL135824 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WILLER, CRISTEN J · 2017 to 2022
$5.4MTraining Program in BioinformaticsT32GM070449 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ATHEY, BRIAN DAVID, BURMEISTER, MARGIT · 2005 to 2020
$3.6MPartners Healthcare Training Program in Precision and Genomic MedicineT32HG010464 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI HEIDI L REHM, JORDAN W SMOLLER · 2019 to 2026
$3.1MMedical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MC_UU_00011/1NCI NIH HHS P30 CA016058NCI NIH HHS P50 CA168505NHGRI NIH HHS T32 HG000040NHGRI NIH HHS T32 HG010464NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL109946NHLBI NIH HHS R35 HL135824NIA NIH HHS K24 AG042765NIDDK NIH HHS P30 DK020572NIDDK NIH HHS R01 DK040344NIDDK NIH HHS R01 DK062370NIDDK NIH HHS R56 DK062370NIDDK NIH HHS U01 DK062370NIGMS NIH HHS T32 GM070449
Abstract
Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported. Functional experiments show that the thyroglobulin protein-altering variants P118L and G67S impact thyroglobulin secretion. Phenome-wide association analysis in the UK Biobank demonstrates the pleiotropic effects of TSH-associated variants and a polygenic score for higher TSH levels is associated with a reduced risk of thyroid cancer in the UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH index variants as instrumental variables suggests a protective effect of higher TSH levels (indicating lower thyroid function) on risk of thyroid cancer and goiter. Our findings highlight the pleiotropic effects of TSH-associated variants on thyroid function and growth of malignant and benign thyroid tumors.
Indexed as
Genetic PleiotropyGenome-Wide Association StudyGenetic LociGenetic Predisposition to DiseaseGoiterHumansMendelian Randomization AnalysisMultifactorial InheritanceMutation, MissensePhenotypePhysical Chromosome MappingPrevalenceRisk FactorsThyroglobulinThyroid NeoplasmsThyrotropinThyroglobulinThyrotropin
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