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GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer
- Publication Year :
- 2020
-
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.
Details
- Database :
- OAIster
- Notes :
- application/pdf, Nature Communications vol. 11 no. 1, English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1198971155
- Document Type :
- Electronic Resource
- Full Text :
- https://doi.org/10.1038.s41467-020-17718-z