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
Contributor organization: Institute for Molecular Medicine Finland
Helsinki Institute of Life Science HiLIFE
University of Helsinki
Centre of Excellence in Complex Disease Genetics
Research Programs Unit
Aarno Palotie / Principal Investigator
Genomics of Neurological and Neuropsychiatric Disorders
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.
Description: Correction: Volume12, Issue1 Article Number7354 DOI10.1038/s41467-021-27675-w PublishedDEC 16 2021
Subject: ENDOGENOUS SUBCLINICAL HYPERTHYROIDISM
SERUM THYROTROPIN CONCENTRATION
GENOME-WIDE ASSOCIATION
CONGENITAL HYPOTHYROIDISM
COMMON VARIANTS
TSH
RECEPTOR
THYROGLOBULIN
HYPERTENSION
MALIGNANCY
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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