GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer
Nature Communications , Volume 11 - Issue 1
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.
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Zhou, W. (Wei), Brumpton, B. (Ben), Kabil, O. (Omer), Gudmundsson, J, Thorleifsson, G, Weinstock, J. (Josh), … Asvold, B.O. (2020). GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer. Nature Communications, 11(1). doi:10.1038/s41467-020-17718-z