Global multi-ancestry genetic study elucidates genes and biological pathways associated with thyroid cancer and benign thyroid diseases.
| Title: | Global multi-ancestry genetic study elucidates genes and biological pathways associated with thyroid cancer and benign thyroid diseases. |
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| Authors: | White SL; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Brasher MS; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Pattee J; Center for Innovative Design & Analysis, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Zhou W; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.; Chapman S; The Broad Institute, Cambridge, MA, USA.; Jee YH; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Bell CC; Division of Endocrinology, Diabetes and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Jamil TL; Department of Otolaryngology, Head and Neck Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.; Barrio M; Division of GI, Trauma, and Endocrine Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA.; Hirbo J; Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Genetic Institute, Vanderbilt University Medical Center, Nashville, TN, USA.; Cox NJ; Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Genetic Institute, Vanderbilt University Medical Center, Nashville, TN, USA.; Straub P; Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USAz.; Vanderbilt Genetic Institute, Vanderbilt University Medical Center, Nashville, TN, USA.; Namba S; Department of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.; Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.; Bertucci-Richter E; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.; Guare L; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; EdrisMohammed A; Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Morris S; Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Mulford AJ; Genomic Health Initiative, Endeavor Health Research Institute, Evanston, IL, USA.; Zhang H; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Fennessy B; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Tobin MD; Department of Population Health Sciences, University of Leicester, Leicester, UK.; University Hospitals of Leicester NHS Trust, Leicester, LE15WW, UK.; Chen J; Department of Population Health Sciences, University of Leicester, Leicester, UK.; Williams AT; Department of Population Health Sciences, University of Leicester, Leicester, UK.; John C; Department of Population Health Sciences, University of Leicester, Leicester, UK.; University Hospitals of Leicester NHS Trust, Leicester, LE15WW, UK.; van Heel DA; Blizard Institute, Queen Mary University of London, London E1 2AB, UK.; Mathur R; Wolfson Institute of Population Health, Queen Mary University of London, London E1 2AB, UK.; Finer S; Wolfson Institute of Population Health, Queen Mary University of London, London E1 2AB, UK.; Moksnes MR; HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.; Brumpton B; HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.; Åsvold BO; HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.; Peculis R; Latvian Biomedical Research and Study Centre, Ratsupites 1-1, Riga, LV-1067, Latvia.; Rovite V; Latvian Biomedical Research and Study Centre, Ratsupites 1-1, Riga, LV-1067, Latvia.; Konrade I; Department of Internal Medicine, Riga Stradins University, Dzirciema Str 16, LV-1007 Riga, Latvia.; Wang Y; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Crooks K; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Chavan S; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Fisher MJ; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Rafaels N; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Lin M; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Shortt J; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Sanders AR; Genomic Health Initiative, Endeavor Health Research Institute, Evanston, IL, USA.; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.; Whiteman D; QIMR Berghofer Medical Research Institute: Herston, QLD, AU.; MacGregor S; QIMR Berghofer Medical Research Institute: Herston, QLD, AU.; Medland S; QIMR Berghofer Medical Research Institute: Herston, QLD, AU.; Thorsteinsdóttir U; deCODE genetics/Amgen, Inc., Reykjavik, Iceland.; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.; Stefánsson K; deCODE genetics/Amgen, Inc., Reykjavik, Iceland.; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.; Karaderi T; Center for Health Data Science, Section for Health Data Science and Artificial Intelligence, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Egan KM; Moffitt Cancer Center.; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.; Bocklage T; University of Kentucky Markey Cancer Center.; University of Kentucky-Department of Pathology and Laboratory Medicine, University of Kentucky-Chandler Medical Center, Lexington, KY, USA.; McCrary HC; University of Utah Huntsman Cancer Institute.; Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.; Riedlingeer G; Rutgers Cancer Institute of New Jersey Department of Medicine, Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.; Salhia B; Norris Comprehensive Cancer Center and Keck School of Medicine of University of Southern California.; Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.; Shriver C; Muthra Cancer Center.; Murtha Cancer Center, Uniformed Services University/Walter Reed National Military Medical Center, Bethesda, MD, USA.; Phan MD; University of Oklahoma Stephenson Cancer Center.; Medical Oncology/Head and Neck Oncology, Stephenson Cancer Center, University of Oklahoma, Oklahoma City, Oklahoma, USA.; Farlow JL; Indiana University School of Medicine, Indianapolis, Indiana.; Edge S; Roswell Park Comprehensive Cancer Center.; Departments of Surgical Oncology and Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.; Kaur V; University of Virginia Cancer Center.; Department of Internal Medicine, Division of Hematology & Oncology, University of Virginia Health, Charlottesville, VA, USA.; Churchman M; Aster Insights, Hudson, FL, USA.; Rounbehler RJ; Aster Insights, Hudson, FL, USA.; Brock PL; The Ohio State University Comprehensive Cancer Center and the Ohio State University College of Medicine, Columbus, OH, USA.; Ringel MD; The Ohio State University Comprehensive Cancer Center and the Ohio State University College of Medicine, Columbus, OH, USA.; Pividori M; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Schweppe R; Division of Endocrinology, Diabetes and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Raeburn CD; Division of GI, Trauma, and Endocrine Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA.; Walters R; Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Chen Z; Nuffield Department of Population Health, University of Oxford, Oxford, UK.; Li L; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.; Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China.; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China.; Matsuda K; Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.; Laboratory of Clinical Genome Sequencing, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.; Okada Y; Department of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.; Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.; Zoellner S; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.; Verma A; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Preuss M; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Kenny E; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Hendricks A; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Fishbein L; Division of Endocrinology, Diabetes and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Research Service, Rocky Mountain Regional VA Medical Center, Aurora, CO, USA.; Kraft P; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Transdivisional Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, USA.; Daly M; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Neale B; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Martin A; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.; Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA.; Cole JB; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Human Medical Genetics and Genomics Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Haugen BR; Division of Endocrinology, Diabetes and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Gignoux CR; Human Medical Genetics and Genomics Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Pozdeyev N; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Division of Endocrinology, Diabetes and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. |
| Corporate Authors: | biobank at the Colorado Center for Personalized Medicine; Genes & Health Research Team; BioBank Japan Project |
| Source: | MedRxiv : the preprint server for health sciences [medRxiv] 2025 May 16. Date of Electronic Publication: 2025 May 16. |
| Publication Type: | Journal Article; Preprint |
| Language: | English |
| Journal Info: | Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE |
| Abstract: | Thyroid diseases are common and highly heritable. Under the Global Biobank Meta-analysis Initiative, we performed a meta-analysis of genome-wide association studies from 19 biobanks for five thyroid diseases: thyroid cancer, benign nodular goiter, Graves' disease, lymphocytic thyroiditis, and primary hypothyroidism. We analyzed genetic association data from ~2.9 million genomes and identified 235 known and 501 novel independent variants significantly linked to thyroid diseases. We discovered genetic correlations between thyroid cancer, benign nodular goiter, and autoimmune thyroid diseases (r 2 =0.21-0.97). Telomere maintenance genes contribute to benign and malignant thyroid nodular disease risk, whereas cell cycle, DNA repair, and DNA damage response genes are predominantly associated with thyroid cancer. We proposed a paradigm explaining genetic predisposition to benign and malignant thyroid nodules. We evaluated thyroid cancer polygenic risk scores (PRS) for clinical applications in thyroid cancer diagnosis. We found PRS associations with thyroid cancer risk features: multifocality, lymph node metastases, and extranodal extension. |
| Comments: | Update in: Nat Genet. 2026 Feb;58(2):307-316. doi: 10.1038/s41588-025-02483-w.. (PMID: 41644669) |
| Grant Information: | R00 HG011898 United States HG NHGRI NIH HHS; I01 BX006252 United States BX BLRD VA; UM1 TR004409 United States TR NCATS NIH HHS; R21 CA282380 United States CA NCI NIH HHS; United Kingdom WT_ Wellcome Trust |
| Entry Date(s): | Date Created: 20250604 Date Completed: 20260210 Latest Revision: 20260306 |
| Update Code: | 20260306 |
| PubMed Central ID: | PMC12132132 |
| DOI: | 10.1101/2025.05.15.25327513 |
| PMID: | 40463558 |
| Database: | MEDLINE |
Journal Article; Preprint