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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; [...]

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

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  • Medientyp: E-Artikel
  • Titel: GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer
  • Beteiligte: 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; [...]
  • Erschienen: Springer Science and Business Media LLC, 2020
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-020-17718-z
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>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.</jats:p>
  • Zugangsstatus: Freier Zugang