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Global multi-ancestry genome-wide analyses identify genes and biological pathways associated with thyroid cancer and benign thyroid diseases

Abstract:
Thyroid diseases are common and highly heritable. We performed a metaanalysis 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 313 known and 570 novel independent loci significantly linked to thyroid diseases. We discovered genetic correlations between thyroid cancer, benign nodular goiter, and autoimmune thyroid diseases (rg=0.16-0.97). Telomere maintenance genes contributed to benign and malignant thyroid nodular disease risk, whereas cell cycle, DNA repair and damage response genes were associated with thyroid cancer. We proposed a paradigm explaining genetic predisposition to benign and malignant thyroid nodules. We found PRS associations with thyroid cancer risk of structural disease recurrence, tumor size, multifocality, lymph node metastases, and extranodal extension. PRS identified individuals with aggressive thyroid cancer in a biobank, creating an opportunity for genetically-informed population screening.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41588-025-02483-w

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
Nuffield Department of Population Health
Sub department:
Clinical Trial Service Unit
Role:
Author
ORCID:
0000-0002-4049-5402
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Nuffield Department of Population Health
Sub department:
Clinical Trial Service Unit
Role:
Author
ORCID:
0000-0003-4067-1100


Publisher:
Springer Nature
Journal:
Nature Genetics More from this journal
Volume:
58
Issue:
2
Pages:
307–316
Publication date:
2026-02-05
Acceptance date:
2025-12-12
DOI:
EISSN:
1546-1718
ISSN:
1061-4036


Language:
English
Keywords:
Pubs id:
2357161
Local pid:
pubs:2357161
Deposit date:
2026-01-08
ARK identifier:

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