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GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer.

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Authors
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 E
Arvan, Peter
Brummett, Chad M
Boehnke, Michael
de la Chapelle, Albert
Stefansson, Kari
Hveem, Kristian
Willer, Cristen J
Åsvold, Bjørn Olav
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Issue Date
2020-08-07

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Zhou W, Brumpton B, Kabil O, et al. GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer. Nat Commun. 2020;11(1):3981. Published 2020 Aug 7. doi:10.1038/s41467-020-17718-z
Abstract
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.
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https://www.nature.com/articles/s41467-020-17718-z
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414135/
ae974a485f413a2113503eed53cd6c53
10.1038/s41467-020-17718-z
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