White Samantha L, Brasher Maizy S, Pattee Jack, Zhou Wei, Chapman Sinéad, Jee Yon Ho, Bell Caitlin C, Jamil Taylor L, Barrio Martin, Hirbo Jibril, Cox Nancy J, Straub Peter, Namba Shinichi, Bertucci-Richter Emily, Guare Lindsay, EdrisMohammed 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 Riise, Brumpton Ben, Åsvold Bjørn Olav, Peculis Raitis, Rovite Vita, Konrade Ilze, Wang Ying, Crooks Kristy, Chavan Sameer, Fisher Matthew J, Rafaels Nicholas, Lin Meng, Shortt Jonathan, Sanders Alan R, Whiteman David, MacGregor Stuart, Medland Sarah, Thorsteinsdóttir Unnur, Stefánsson Kári, Karaderi Tugce, Egan Kathleen M, Bocklage Therese, McCrary Hilary C, Riedlingeer Greg, Salhia Bodour, Shriver Craig, Phan Minh D, Farlow Janice L, Edge Stephen, Kaur Varinder, Churchman Michelle, Rounbehler Robert J, Brock Pamela L, Ringel Matthew D, Pividori Milton, Schweppe Rebecca, Raeburn Christopher D, Walters Robin, Chen Zhengming, Li Liming, Matsuda Koichi, Okada Yukinori, Zoellner Sebastian, Verma Anurag, Preuss Michael, Kenny Eimear, Hendricks Audrey, Fishbein Lauren, Kraft Peter, Daly Mark, Neale Benjamin, Martin Alicia, Cole Joanne B, Haugen Bryan R, Gignoux Christopher R, Pozdeyev Nikita
Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Center for Innovative Design & Analysis, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
medRxiv. 2025 May 16:2025.05.15.25327513. doi: 10.1101/2025.05.15.25327513.
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 ( =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.
甲状腺疾病很常见且具有高度遗传性。在全球生物样本库荟萃分析倡议下，我们对来自19个生物样本库的全基因组关联研究进行了荟萃分析，涉及五种甲状腺疾病：甲状腺癌、良性结节性甲状腺肿、格雷夫斯病、淋巴细胞性甲状腺炎和原发性甲状腺功能减退症。我们分析了约290万个基因组的遗传关联数据，确定了235个已知的和501个新的与甲状腺疾病显著相关的独立变异。我们发现甲状腺癌、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（ =0.21-0.97）。端粒维持基因会增加良性和恶性甲状腺结节疾病的风险，而细胞周期、DNA修复和DNA损伤反应基因主要与甲状腺癌相关。我们提出了一个解释良性和恶性甲状腺结节遗传易感性的范例。我们评估了甲状腺癌多基因风险评分（PRS）在甲状腺癌诊断中的临床应用。我们发现PRS与甲状腺癌风险特征相关：多灶性、淋巴结转移和结外扩展。
Zotero 插件
