Standard
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 › fagfællebedømt
Harvard
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, 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 2024, '
Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications',
Nature Communications, bind 15, nr. 1, 888.
https://doi.org/10.1038/s41467-024-44701-9
APA
Sterenborg, R. B. T. M., Steinbrenner, I., Li, Y., Bujnis, M. N., Naito, T., Marouli, E., Galesloot, T. E., Babajide, O.
, Andreasen, L., Astrup, A., Åsvold, B. O., Bandinelli, S., Beekman, M., Beilby, J. P., Bork-Jensen, J., Boutin, T., Brody, J. A., Brown, S. J., Brumpton, B., ... Medici, M. (2024).
Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.
Nature Communications,
15(1), [888].
https://doi.org/10.1038/s41467-024-44701-9
Vancouver
Sterenborg RBTM, Steinbrenner I, Li Y, Bujnis MN, Naito T, Marouli E o.a.
Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.
Nature Communications. 2024;15(1). 888.
https://doi.org/10.1038/s41467-024-44701-9
Author
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. / Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications. I: Nature Communications. 2024 ; Bind 15, Nr. 1.
Bibtex
@article{8c9f224821e8471b8312db99b841124e,
title = "Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications",
abstract = "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.",
author = "Sterenborg, {Rosalie B.T.M.} and Inga Steinbrenner and Yong Li and Bujnis, {Melissa N.} and Tatsuhiko Naito and Eirini Marouli and Galesloot, {Tessel E.} and Oladapo Babajide and Laura Andreasen and Arne Astrup and {\AA}svold, {Bj{\o}rn Olav} and Stefania Bandinelli and Marian Beekman and Beilby, {John P.} and Jette Bork-Jensen and Thibaud Boutin and Brody, {Jennifer A.} and Brown, {Suzanne J.} and Ben Brumpton and Campbell, {Purdey J.} and Cappola, {Anne R.} and Graziano Ceresini and Layal Chaker and Chasman, {Daniel I.} and Concas, {Maria Pina} and {Coutinho de Almeida}, Rodrigo and Cross, {Simone M.} and Francesco Cucca and Deary, {Ian J.} and Kjaergaard, {Alisa Devedzic} and {Echouffo Tcheugui}, {Justin B.} and Christina Ellervik and Eriksson, {Johan G.} and Luigi Ferrucci and Jan Freudenberg and Christian Fuchsberger and Christian Gieger and Franco Giulianini and Martin G{\"o}gele and Graham, {Sarah E.} and Niels Grarup and Ivana Gunja{\v c}a and Torben Hansen and Harding, {Barbara N.} and Harris, {Sarah E.} and Stig Hauns{\o} and Caroline Hayward and Jennie Hui and Till Ittermann and Jukema, {J. Wouter} and Eero Kajantie and Kanters, {J{\o}rgen K.} and K{\aa}rhus, {Line L.} and Kiemeney, {Lambertus A.L.M.} and Margreet Kloppenburg and Brigitte K{\"u}hnel and Jari Lahti and Claudia Langenberg and Bruno Lapauw and Graham Leese and Shuo Li and Liewald, {David C.M.} and Allan Linneberg and Lominchar, {Jesus V.T.} and Jian{\textquoteright}an Luan and Martin, {Nicholas G.} and Antonela Matana and Meima, {Marcel E.} and Thomas Meitinger and Ingrid Meulenbelt and Mitchell, {Braxton D.} and M{\o}llehave, {Line T.} and Samia Mora and Silvia Naitza and Matthias Nauck and Netea-Maier, {Romana T.} and Raymond Noordam and Casia Nursyifa and Yukinori Okada and Stefano Onano and Areti Papadopoulou and Palmer, {Colin N.A.} and Cristian Pattaro and Oluf Pedersen and Annette Peters and Maik Pietzner and Ozren Pola{\v s}ek and Pramstaller, {Peter P.} and Psaty, {Bruce M.} and Ante Punda and Debashree Ray and Paul Redmond and Richards, {J. Brent} and Ridker, {Paul M.} and Russ, {Tom C.} and Ryan, {Kathleen A.} and Olesen, {Morten Salling} and Schultheiss, {Ulla T.} and Elizabeth Selvin and Siddiqui, {Moneeza K.} and Carlo Sidore and Slagboom, {P. Eline} and S{\o}rensen, {Thorkild I.A.} and Enrique Soto-Pedre and Spector, {Tim D.} and Beatrice Spedicati and Sundararajan Srinivasan and Starr, {John M.} and Stott, {David J.} and Toshiko Tanaka and Vesela Torlak and Stella Trompet and Johanna Tuhkanen and Uitterlinden, {Andr{\'e} G.} and {van den Akker}, {Erik B.} and {van den Eynde}, Tibbert and {van der Klauw}, {Melanie M.} and {van Heemst}, Diana and Charlotte Verroken and Visser, {W. Edward} and Dina Vojinovic and Henry V{\"o}lzke and Melanie Waldenberger and Walsh, {John P.} and Wareham, {Nicholas J.} and Stefan Weiss and Willer, {Cristen J.} and Wilson, {Scott G.} and Wolffenbuttel, {Bruce H.R.} and Wouters, {Hanneke J.C.M.} and Wright, {Margaret J.} and Qiong Yang and Tatijana Zemunik and Wei Zhou and Gu Zhu and Sebastian Z{\"o}llner and Smit, {Johannes W.A.} and Peeters, {Robin P.} and Anna K{\"o}ttgen and Alexander Teumer and Marco Medici",
note = "Publisher Copyright: {\textcopyright} 2024, The Author(s).",
year = "2024",
doi = "10.1038/s41467-024-44701-9",
language = "English",
volume = "15",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",
}
RIS
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 -