Samantha White, Maizy S. Brasher, Jack Pattee, W Zhou, Sinéad Chapman, Yon Ho Jee, Caitlin C. Bell, Taylor L. Jamil, Martin Barrio, Christopher H. Arehart, Luke M. Evans, Jibril Hirbo, Nancy J. Cox, P. Straub, Shinichi Namba, Emily M. Bertucci, Lindsay Guare, Ahmed Edris, Sam Morris, Ashley J. Mulford, Haoyu Zhang, Brian Fennessy, Martin D. Tobin, J Chen, Alexander T. Williams, C. Bridges John, David A. van Heel, Rohini Mathur, Sarah Finer, Marta R. Moksnes, Ben M. Brumpton, Bjørn Olav Åsvold, Raitis Pečulis, Vita Rovīte, Ilze Konrāde, Ying Wang, Kristy Crooks, Sameer Chavan, Matthew J. Fisher, Nicholas Rafaels, Meng Lin, Jonathan A. Shortt, A R Sanders, David C. Whiteman, Stuart MacGregor, Sarah E. Medland, Unnur Thorsteinsdóttir, Kári Stefánsson, Tugce Karaderi, Kathleen M. Egan, Therese Bocklage, Hilary C. McCrary, Gregory Riedlinger, Bodour Salhia, CD Shriver, Minh D. Phan, Janice L. Farlow, Stephen B. Edge, Varinder Kaur, Michelle L. Churchman, Robert J. Rounbehler, Pamela Brock, Matthew D. Ringel, Milton Pividori, Rebecca E. Schweppe, Christopher D. Raeburn, Robin G. Walters, Z Chen, Liming Li, Koichi Matsuda, Yukinori Okada, Sebastian Zöllner, Anurag Verma, Penn Medicine BioBank, Michael H. Preuss, Eimear Kenny, Audrey E. Hendricks, Lauren Fishbein, Peter Kraft, Mark J. Daly, Benjamin M. Neale, David A. van Heel, The BioBank Japan Project, Alicia R. Martin, Joanne B. Cole, B. Haugen, Global Biobank Meta-analysis Initiative, C. R. Gignoux, Nikita Pozdeyev
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.