info:eu-repo/semantics/article
GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer
Fecha
2020-08Registro en:
Zhou, Wei; Brumpton, Ben; Kabil, Omer; Gudmundsson, Julius; Thorleifsson, Gudmar; et al.; GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer; Springer; Nature Communications; 11; 1; 8-2020; 1-13
2041-1723
CONICET Digital
CONICET
Autor
Zhou, Wei
Brumpton, Ben
Kabil, Omer
Gudmundsson, Julius
Thorleifsson, Gudmar
Weinstock, Josh
Zawistowski, Matthew
Nielsen, Jonas B.
Chaker, Layal
Medici, Marco
Teumer, Alexander
Naitza, Silvia
Sanna, Serena
Schultheiss, Ulla T.
Cappola, Anne
Karjalainen, Juha
Kurki, Mitja
Oneka, Morgan
Taylor, Peter
Fritsche, Lars G.
Graham, Sarah E.
Wolford, Brooke N.
Overton, William
Rasheed, Humaira
Haug, Eirin B.
Gabrielsen, Maiken E.
Skogholt, Anne Heidi
Surakka, Ida
Davey Smith, George
Pandit, Anita
Roychowdhury, Tanmoy
Hornsby, Whitney E.
Jonasson, Jon G.
Senter, Leigha
Liyanarachchi, Sandya
Ringel, Matthew D.
Xu, Li
Kiemeney, Lambertus A.
He, Huiling
Netea-Maier, Romana T.
Mayordomo, Jose I.
Plantinga, Theo S.
Hrafnkelsson, Jon
Hjartarson, Hannes
Sturgis, Erich M.
Palotie, Aarno
Daly, Mark
Citterio, Cintia Eliana
Arvan, Peter
Brummett, Chad M.
Boehnke, Michael
de la Chapelle, Albert
Stefansson, Kari
Hveem, Kristian
Willer, Cristen J.
Åsvold, Bjørn Olav
Resumen
Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported. Functional experiments show that the thyroglobulin protein-altering variants P118L and G67S impact thyroglobulin secretion. Phenome-wide association analysis in the UK Biobank demonstrates the pleiotropic effects of TSH-associated variants and a polygenic score for higher TSH levels is associated with a reduced risk of thyroid cancer in the UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH index variants as instrumental variables suggests a protective effect of higher TSH levels (indicating lower thyroid function) on risk of thyroid cancer and goiter. Our findings highlight the pleiotropic effects of TSH-associated variants on thyroid function and growth of malignant and benign thyroid tumors.