| Title: |
Global multi-ancestry genome-wide analyses identify genes and biological pathways associated with thyroid cancer and benign thyroid diseases |
| Authors: |
White, Samantha L.; Brasher, Maizy S.; Pattee, Jack; Zhou, Wei; Chapman, Sinéad; Jee, Yon Ho; Bell, Caitlin C.; Jamil, Taylor L.; Barrio, Martin; Arehart, Christopher H.; Evans, Luke M.; Hirbo, Jibril; Cox, Nancy J.; Straub, Peter; Namba, Shinichi; Bertucci-Richter, Emily; Guare, Lindsay; Edris, Ahmed; Morris, Sam; Mulford, Ashley J.; Zhang, Haoyu; Fennessy, Brian; Tobin, Martin D.; Chen, Jing; Williams, Alexander T.; John, Catherine; van Heel, David A.; Mathur, Rohini; Finer, Sarah; Moksnes, Marta R.; Brumpton, Ben M.; Åsvold, Bjørn Olav; Peculis, Raitis; Rovite, Vita; Konrade, Ilze; Wang, Ying; Crooks, Kristy; Chavan, Sameer; Fisher, Matthew J.; Rafaels, Nicholas; Lin, Meng; Shortt, Jonathan A.; Sanders, Alan R.; Whiteman, David C.; MacGregor, Stuart; Medland, Sarah E.; Thorsteinsdóttir, Unnur; Stefánsson, Kári; Karaderi, Tugce; Egan, Kathleen M.; Bocklage, Therese; McCrary, Hilary C.; Riedlinger, Gregory; Salhia, Bodour; Shriver, Craig; Phan, Minh D.; Farlow, Janice L.; Edge, Stephen; Kaur, Varinder; Churchman, Michelle L.; Rounbehler, Robert J.; Brock, Pamela L.; Ringel, Matthew D.; Pividori, Milton; Schweppe, Rebecca; Raeburn, Christopher D.; Walters, Robin G.; Chen, Zhengming; Li, Liming; Matsuda, Koichi; Okada, Yukinori; Zöllner, Sebastian; Verma, Anurag; Penn Medicine BioBank; Preuss, Michael H.; Kenny, Eimear; Hendricks, Audrey E.; Fishbein, Lauren; Kraft, Peter; Daly, Mark J.; Neale, Benjamin M.; Virtual Thyroid Biopsy Consortium; Colorado Center for Personalized Medicine; Genes & Health Research Team; BioBank Japan Project; Martin, Alicia R.; Cole, Joanne B.; Haugen, Bryan R.; Global Biobank Meta-analysis Initiative; Gignoux, Christopher R.; Pozdeyev, Nikita |
| Contributors: |
Otolaryngology -- Head and Neck Surgery, School of Medicine |
| Source: |
PMC |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2026 |
| Collection: |
Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| Subject Terms: |
Genome-wide association studies; Thyroid cancer; Genetic predisposition to disease; Thyroid neoplasms |
| Description: |
Thyroid diseases are common and highly heritable. We performed a meta-analysis of genome-wide association studies from 19 biobanks for five thyroid diseases: thyroid cancer (ThC), 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 new independent loci linked to thyroid diseases. We discovered genetic correlations between ThC, 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 ThC. We propose a paradigm that explains genetic predisposition to benign and malignant thyroid nodules. We found polygenic risk score associations with ThC risk of structural disease recurrence, tumor size, multifocality, lymph node metastases and extranodal extension. Polygenic risk scores identified individuals with aggressive ThC in a biobank, creating an opportunity for genetically informed population screening. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Nature Genetics; https://hdl.handle.net/1805/54605 |
| Availability: |
https://hdl.handle.net/1805/54605 |
| Rights: |
Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.B9D17E93 |
| Database: |
BASE |