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GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer.
- Source :
-
Nature communications [Nat Commun] 2020 Aug 07; Vol. 11 (1), pp. 3981. Date of Electronic Publication: 2020 Aug 07. - 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.
- Subjects :
- Genetic Loci
Genetic Predisposition to Disease
Goiter genetics
Humans
Mendelian Randomization Analysis
Multifactorial Inheritance genetics
Mutation, Missense genetics
Phenotype
Physical Chromosome Mapping
Prevalence
Risk Factors
Thyroglobulin genetics
Thyroid Neoplasms epidemiology
Genetic Pleiotropy
Genome-Wide Association Study
Thyroid Neoplasms genetics
Thyrotropin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 32769997
- Full Text :
- https://doi.org/10.1038/s41467-020-17718-z