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

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

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Nature communications. - 11 (2020) , 3981, ISSN: 2041-1723

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2020
• Urheber: Zhou, Wei ; Brumpton, Ben ; Kabil, Omer ; Gudmundsson, Julius ; Thorleifsson, Gudmar ; Schultheiß, Ulla Teresa ; La Chapelle, Albert de ; Stefansson, Kari ; Hveem, Kristian ; Willer, Cristen ; Åsvold, Bjørn Olav

Weitere Informationen

• DOI: 10.1038/s41467-020-17718-z
• URN: urn:nbn:de:bsz:25-freidok-1669495
• Rechteinformation: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 14.08.2025, 10:45 MESZ