Abstract
Originalsprog | Engelsk |
---|---|
Artikelnummer | 888 |
Tidsskrift | Nature Communications |
Vol/bind | 15 |
Udgave nummer | 1 |
Antal sider | 18 |
ISSN | 2041-1723 |
DOI | |
Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:This work was supported by funding from the European and American Thyroid Associations, the Erasmus University Rotterdam, the Dutch Organization for Scientific Research (NWO) (M.Med.), and the NIH (grants R35GM118335 and T32DK110966). Acknowledgments and study-specific acknowledgments are provided in the Supplementary Note. We conducted this research using the UK Biobank resource under the application numbers 53723 and 20272.
Funding Information:
This work was supported by funding from the European and American Thyroid Associations, the Erasmus University Rotterdam, the Dutch Organization for Scientific Research (NWO) (M.Med.), and the NIH (grants R35GM118335 and T32DK110966). Acknowledgments and study-specific acknowledgments are provided in the Supplementary Note. We conducted this research using the UK Biobank resource under the application numbers 53723 and 20272.
Publisher Copyright:
© 2024, The Author(s).
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Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications. / Sterenborg, Rosalie B.T.M.; Steinbrenner, Inga; Li, Yong; Bujnis, Melissa N.; Naito, Tatsuhiko; Marouli, Eirini; Galesloot, Tessel E.; Babajide, Oladapo; Andreasen, Laura; Astrup, Arne; Åsvold, Bjørn Olav; Bandinelli, Stefania; Beekman, Marian; Beilby, John P.; Bork-Jensen, Jette; Boutin, Thibaud; Brody, Jennifer A.; Brown, Suzanne J.; Brumpton, Ben; Campbell, Purdey J.; Cappola, Anne R.; Ceresini, Graziano; Chaker, Layal; Chasman, Daniel I.; Concas, Maria Pina; Coutinho de Almeida, Rodrigo; Cross, Simone M.; Cucca, Francesco; Deary, Ian J.; Kjaergaard, Alisa Devedzic; Echouffo Tcheugui, Justin B.; Ellervik, Christina; Eriksson, Johan G.; Ferrucci, Luigi; Freudenberg, Jan; Fuchsberger, Christian; Gieger, Christian; Giulianini, Franco; Gögele, Martin; Graham, Sarah E.; Grarup, Niels; Gunjača, Ivana; Hansen, Torben; Harding, Barbara N.; Harris, Sarah E.; Haunsø, Stig; Hayward, Caroline; Hui, Jennie; Ittermann, Till; Jukema, J. Wouter; Kajantie, Eero; Kanters, Jørgen K.; Kårhus, Line L.; Kiemeney, Lambertus A.L.M.; Kloppenburg, Margreet; Kühnel, Brigitte; Lahti, Jari; Langenberg, Claudia; Lapauw, Bruno; Leese, Graham; Li, Shuo; Liewald, David C.M.; Linneberg, Allan; Lominchar, Jesus V.T.; Luan, Jian’an; Martin, Nicholas G.; Matana, Antonela; Meima, Marcel E.; Meitinger, Thomas; Meulenbelt, Ingrid; Mitchell, Braxton D.; Møllehave, Line T.; Mora, Samia; Naitza, Silvia; Nauck, Matthias; Netea-Maier, Romana T.; Noordam, Raymond; Nursyifa, Casia; Okada, Yukinori; Onano, Stefano; Papadopoulou, Areti; Palmer, Colin N.A.; Pattaro, Cristian; Pedersen, Oluf; Peters, Annette; Pietzner, Maik; Polašek, Ozren; Pramstaller, Peter P.; Psaty, Bruce M.; Punda, Ante; Ray, Debashree; Redmond, Paul; Richards, J. Brent; Ridker, Paul M.; Russ, Tom C.; Ryan, Kathleen A.; Olesen, Morten Salling; Schultheiss, Ulla T.; Selvin, Elizabeth; Siddiqui, Moneeza K.; Sidore, Carlo; Slagboom, P. Eline; Sørensen, Thorkild I.A.; Soto-Pedre, Enrique; Spector, Tim D.; Spedicati, Beatrice; Srinivasan, Sundararajan; Starr, John M.; Stott, David J.; Tanaka, Toshiko; Torlak, Vesela; Trompet, Stella; Tuhkanen, Johanna; Uitterlinden, André G.; van den Akker, Erik B.; van den Eynde, Tibbert; van der Klauw, Melanie M.; van Heemst, Diana; Verroken, Charlotte; Visser, W. Edward; Vojinovic, Dina; Völzke, Henry; Waldenberger, Melanie; Walsh, John P.; Wareham, Nicholas J.; Weiss, Stefan; Willer, Cristen J.; Wilson, Scott G.; Wolffenbuttel, Bruce H.R.; Wouters, Hanneke J.C.M.; Wright, Margaret J.; Yang, Qiong; Zemunik, Tatijana; Zhou, Wei; Zhu, Gu; Zöllner, Sebastian; Smit, Johannes W.A.; Peeters, Robin P.; Köttgen, Anna; Teumer, Alexander; Medici, Marco.
I: Nature Communications, Bind 15, Nr. 1, 888, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications
AU - Sterenborg, Rosalie B.T.M.
AU - Steinbrenner, Inga
AU - Li, Yong
AU - Bujnis, Melissa N.
AU - Naito, Tatsuhiko
AU - Marouli, Eirini
AU - Galesloot, Tessel E.
AU - Babajide, Oladapo
AU - Andreasen, Laura
AU - Astrup, Arne
AU - Åsvold, Bjørn Olav
AU - Bandinelli, Stefania
AU - Beekman, Marian
AU - Beilby, John P.
AU - Bork-Jensen, Jette
AU - Boutin, Thibaud
AU - Brody, Jennifer A.
AU - Brown, Suzanne J.
AU - Brumpton, Ben
AU - Campbell, Purdey J.
AU - Cappola, Anne R.
AU - Ceresini, Graziano
AU - Chaker, Layal
AU - Chasman, Daniel I.
AU - Concas, Maria Pina
AU - Coutinho de Almeida, Rodrigo
AU - Cross, Simone M.
AU - Cucca, Francesco
AU - Deary, Ian J.
AU - Kjaergaard, Alisa Devedzic
AU - Echouffo Tcheugui, Justin B.
AU - Ellervik, Christina
AU - Eriksson, Johan G.
AU - Ferrucci, Luigi
AU - Freudenberg, Jan
AU - Fuchsberger, Christian
AU - Gieger, Christian
AU - Giulianini, Franco
AU - Gögele, Martin
AU - Graham, Sarah E.
AU - Grarup, Niels
AU - Gunjača, Ivana
AU - Hansen, Torben
AU - Harding, Barbara N.
AU - Harris, Sarah E.
AU - Haunsø, Stig
AU - Hayward, Caroline
AU - Hui, Jennie
AU - Ittermann, Till
AU - Jukema, J. Wouter
AU - Kajantie, Eero
AU - Kanters, Jørgen K.
AU - Kårhus, Line L.
AU - Kiemeney, Lambertus A.L.M.
AU - Kloppenburg, Margreet
AU - Kühnel, Brigitte
AU - Lahti, Jari
AU - Langenberg, Claudia
AU - Lapauw, Bruno
AU - Leese, Graham
AU - Li, Shuo
AU - Liewald, David C.M.
AU - Linneberg, Allan
AU - Lominchar, Jesus V.T.
AU - Luan, Jian’an
AU - Martin, Nicholas G.
AU - Matana, Antonela
AU - Meima, Marcel E.
AU - Meitinger, Thomas
AU - Meulenbelt, Ingrid
AU - Mitchell, Braxton D.
AU - Møllehave, Line T.
AU - Mora, Samia
AU - Naitza, Silvia
AU - Nauck, Matthias
AU - Netea-Maier, Romana T.
AU - Noordam, Raymond
AU - Nursyifa, Casia
AU - Okada, Yukinori
AU - Onano, Stefano
AU - Papadopoulou, Areti
AU - Palmer, Colin N.A.
AU - Pattaro, Cristian
AU - Pedersen, Oluf
AU - Peters, Annette
AU - Pietzner, Maik
AU - Polašek, Ozren
AU - Pramstaller, Peter P.
AU - Psaty, Bruce M.
AU - Punda, Ante
AU - Ray, Debashree
AU - Redmond, Paul
AU - Richards, J. Brent
AU - Ridker, Paul M.
AU - Russ, Tom C.
AU - Ryan, Kathleen A.
AU - Olesen, Morten Salling
AU - Schultheiss, Ulla T.
AU - Selvin, Elizabeth
AU - Siddiqui, Moneeza K.
AU - Sidore, Carlo
AU - Slagboom, P. Eline
AU - Sørensen, Thorkild I.A.
AU - Soto-Pedre, Enrique
AU - Spector, Tim D.
AU - Spedicati, Beatrice
AU - Srinivasan, Sundararajan
AU - Starr, John M.
AU - Stott, David J.
AU - Tanaka, Toshiko
AU - Torlak, Vesela
AU - Trompet, Stella
AU - Tuhkanen, Johanna
AU - Uitterlinden, André G.
AU - van den Akker, Erik B.
AU - van den Eynde, Tibbert
AU - van der Klauw, Melanie M.
AU - van Heemst, Diana
AU - Verroken, Charlotte
AU - Visser, W. Edward
AU - Vojinovic, Dina
AU - Völzke, Henry
AU - Waldenberger, Melanie
AU - Walsh, John P.
AU - Wareham, Nicholas J.
AU - Weiss, Stefan
AU - Willer, Cristen J.
AU - Wilson, Scott G.
AU - Wolffenbuttel, Bruce H.R.
AU - Wouters, Hanneke J.C.M.
AU - Wright, Margaret J.
AU - Yang, Qiong
AU - Zemunik, Tatijana
AU - Zhou, Wei
AU - Zhu, Gu
AU - Zöllner, Sebastian
AU - Smit, Johannes W.A.
AU - Peeters, Robin P.
AU - Köttgen, Anna
AU - Teumer, Alexander
AU - Medici, Marco
N1 - Publisher Copyright: © 2024, The Author(s).
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-024-44701-9
DO - 10.1038/s41467-024-44701-9
M3 - Journal article
C2 - 38291025
AN - SCOPUS:85183777430
VL - 15
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 888
ER -