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

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Zhou , W , Brumpton , B , Kabil , O , Gudmundsson , J , Thorleifsson , G , Weinstock , J , Zawistowski , M , Nielsen , J B , Chaker , L , Medici , M , Teumer , A , Naitza , S , Sanna , S , Schultheiss , U T , Cappola , A , Karjalainen , J , Kurki , M , Oneka , M , Taylor , P , Fritsche , L G , Graham , S E , Wolford , B N , Overton , W , Rasheed , H , Haug , E B , Gabrielsen , M E , Skogholt , A H , Surakka , I , Smith , G D , Pandit , A , Roychowdhury , T , Hornsby , W E , Jonasson , J G , Senter , L , Liyanarachchi , S , Ringel , M D , Xu , L , Kiemeney , L A , He , H , Netea-Maier , R T , Mayordomo , J , Plantinga , T S , Hrafnkelsson , J , Hjartarson , H , Sturgis , E M , Palotie , A , Daly , M , Citterio , C E , Arvan , P , Brummett , C M , Boehnke , M , de la Chapelle , A , Stefansson , K , Hveem , K , Willer , C J & Asvold , B O 2020 , ' GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer ' , Nature Communications , vol. 11 , no. 1 , 3981 . https://doi.org/10.1038/s41467-020-17718-z

Title: GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer
Author: 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; Smith, George Davey; 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; 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.; Asvold, Bjorn Olav
Other contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Centre of Excellence in Complex Disease Genetics
University of Helsinki, Institute for Molecular Medicine Finland






Date: 2020-08-07
Language: eng
Number of pages: 13
Belongs to series: Nature Communications
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-020-17718-z
URI: http://hdl.handle.net/10138/319425
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. Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. Here, the authors conduct a GWAS and suggest protective effect of higher TSH on risk of thyroid cancer and goitre.
Subject: ENDOGENOUS SUBCLINICAL HYPERTHYROIDISM
SERUM THYROTROPIN CONCENTRATION
GENOME-WIDE ASSOCIATION
CONGENITAL HYPOTHYROIDISM
COMMON VARIANTS
TSH
RECEPTOR
THYROGLOBULIN
HYPERTENSION
MALIGNANCY
3111 Biomedicine
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