GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer.
Nat Commun
; 11(1): 3981, 2020 08 07.
Article
in En
| MEDLINE
| ID: mdl-32769997
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.
Full text:
1
Database:
MEDLINE
Main subject:
Thyroid Neoplasms
/
Thyrotropin
/
Genome-Wide Association Study
/
Genetic Pleiotropy
Type of study:
Clinical_trials
/
Etiology_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Year:
2020
Type:
Article