科罗拉多大学Nikita Pozdeyev小组宣布他们发现了全球多祖先全基因组分析确定了与甲状腺癌和良性甲状腺疾病相关的基因和生物学途径。该项研究成果发表在2026年2月5日出版的《自然—遗传学》上。

研究人员对来自19个生物银行的5种甲状腺疾病的全基因组关联研究进行了荟萃分析：甲状腺癌（ThC）、良性结节性甲状腺肿、Graves病、淋巴细胞性甲状腺炎和原发性甲状腺功能减退。该团队分析了约290万个基因组的遗传关联数据，确定了313个已知和570个新的与甲状腺疾病相关的独立位点。课题组人员发现ThC、良性结节性甲状腺肿和自身免疫性甲状腺疾病之间存在遗传相关性（rg =0.16-0.97）。端粒维持基因与良性和恶性甲状腺结节病风险有关，而细胞周期、DNA修复和损伤反应基因与四氢大麻酚相关。研究人员提出一个范式，解释遗传易感性的良性和恶性甲状腺结节。研究团队发现多基因风险评分与结构性疾病复发、肿瘤大小、多灶性、淋巴结转移和结外延伸的ThC风险相关。多基因风险评分在生物库中识别出具有侵袭性四氢大麻酚的个体，为基因知情人群筛查创造了机会。

据悉，甲状腺疾病是常见且高度遗传性的疾病。

附：英文原文

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

Author: White, Samantha L., Brasher, Maizy S., Pattee, Jack, Zhou, Wei, Chapman, Sinad, 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., svold, Bjrn 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., Thorsteinsdttir, Unnur, Stefnsson, Kri, 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.

Issue&Volume: 2026-02-05

Abstract: 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.

DOI: 10.1038/s41588-025-02483-w

Source: https://www.nature.com/articles/s41588-025-02483-w