| Title: |
Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications. |
| Authors: |
Sterenborg, RBTM; Steinbrenner, I; Li, Y; Bujnis, MN; Naito, T; Marouli, E; Galesloot, TE; Babajide, O; Andreasen, L; Astrup, A; Åsvold, BO; Bandinelli, S; Beekman, M; Beilby, JP; Bork-Jensen, J; Boutin, T; Brody, JA; Brown, SJ; Brumpton, B; Campbell, PJ; Cappola, AR; Ceresini, G; Chaker, L; Chasman, DI; Concas, MP; Coutinho de Almeida, R; Cross, SM; Cucca, F; Deary, IJ; Kjaergaard, AD; Echouffo Tcheugui, JB; Ellervik, C; Eriksson, JG; Ferrucci, L; Freudenberg, J; GHS DiscovEHR; Regeneron Genetics Center; Fuchsberger, C; Gieger, C; Giulianini, F; Gögele, M; Graham, SE; Grarup, N; Gunjača, I; Hansen, T; Harding, BN; Harris, SE; Haunsø, S; Hayward, C; Hui, J; Ittermann, T; Jukema, JW; Kajantie, E; Kanters, JK; Kårhus, LL; Kiemeney, LALM; Kloppenburg, M; Kühnel, B; Lahti, J; Langenberg, C; Lapauw, B; Leese, G; Li, S; Liewald, DCM; Linneberg, A; Lominchar, JVT; Luan, J; Martin, NG; Matana, A; Meima, ME; Meitinger, T; Meulenbelt, I; Mitchell, BD; Møllehave, LT; Mora, S; Naitza, S; Nauck, M; Netea-Maier, RT; Noordam, R; Nursyifa, C; Okada, Y; Onano, S; Papadopoulou, A; Palmer, CNA; Pattaro, C; Pedersen, O; Peters, A; Pietzner, M; Polašek, O; Pramstaller, PP; Psaty, BM; Punda, A; Ray, D; Redmond, P; Richards, JB; Ridker, PM; Russ, TC; Ryan, KA; Olesen, MS; Schultheiss, UT; Selvin, E; Siddiqui, MK; Sidore, C; Slagboom, PE; Sørensen, TIA; Soto-Pedre, E; Spector, TD; Spedicati, B; Srinivasan, S; Starr, JM; Stott, DJ; Tanaka, T; Torlak, V; Trompet, S; Tuhkanen, J; Uitterlinden, AG; van den Akker, EB; van den Eynde, T; van der Klauw, MM; van Heemst, D; Verroken, C; Visser, WE; Vojinovic, D; Völzke, H; Waldenberger, M; Walsh, JP; Wareham, NJ; Weiss, S; Willer, CJ; Wilson, SG; Wolffenbuttel, BHR; Wouters, HJCM; Wright, MJ; Yang, Q; Zemunik, T; Zhou, W; Zhu, G; Zöllner, S; Smit, JWA; Peeters, RP; Köttgen, A; Teumer, A; Medici, M |
| Publisher Information: |
Nature Research |
| Publication Year: |
2024 |
| Collection: |
Queen Mary University of London: Queen Mary Research Online (QMRO) |
| Subject Terms: |
Humans; Thyroid Gland; Thyroxine; Genome-Wide Association Study; Triiodothyronine; Thyrotropin |
| Description: |
To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases. |
| Document Type: |
article in journal/newspaper |
| File Description: |
888 - ? |
| Language: |
English |
| Relation: |
Nat Commun; https://qmro.qmul.ac.uk/xmlui/handle/123456789/95973 |
| DOI: |
10.1038/s41467-024-44701-9 |
| Availability: |
https://qmro.qmul.ac.uk/xmlui/handle/123456789/95973; https://doi.org/10.1038/s41467-024-44701-9 |
| Rights: |
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. ; © The Author(s) 2024 |
| Accession Number: |
edsbas.568CE71E |
| Database: |
BASE |