Thyroid function

Thyroid function

Thyroid dysfunction is common, but optimal diagnostic and treatment practices are debated. In the HUNT Study, thyroid function function has been measured since the HUNT2 survey in 1995-97. We use genetic and longitudinal phenotypic data from HUNT linked with hospital and national registry data, as well as study data from international collaborators, to study the occurrence of thyroid disease and the causes and consequences of variation in thyroid function across the population. Our overall aim is to inform and improve clinical practices of diagnosing and treating thyroid dysfunction. 

Thyroid

Genetic determinants and consequences of thyroid function

This project aims to identify genetic variants association with serum TSH concentrations, and to use the identified genetic variants in a Mendelian randomization framework to examine causal effects of variation in thyroid function.  
In a GWAS meta-analysis of up to 119,715 individuals, including the HUNT Study, the Michigan Genomics Initiative and the ThyroidOmics consortium, we identified 28 novel genome-wide significant loci for TSH and thyroglobulin protein-altering variants that impact thyroglobulin secretion. Mendelian randomization analyses identified effects of TSH-associated variants on growth of malignant and benign thyroid tumors (Zhou W et al. GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer. Nat Commun. 2020;11(1):3981. doi: 10.1038/s41467-020-17718-z. PMID: 32769997).
We are following up this work with Mendelian randomization studies examining causal effects of variation in thyroid function. This work is done in collaboration with the ThyroidOmics consortium, in which we have contributed to the latest GWAS of thyroid function traits (Sterenborg RBTM et al. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications. Nat Commun. 2024;15(1):888. doi: 10.1038/s41467-024-44701-9. PMID: 38291025).

Causes and consequences of hypothyroidism: Longitudinal analyses of the HUNT Study

Using longitudinal thyroid function measurements from the 1990s onwards, we are currently examining the natural course of thyroid function through the adult life course. We examine risk factors for hypothyroidism and hyperthyroidism, the impact of genetic and phenotypic risk factors on diagnostic thresholds for thyroid dysfunction, and potential consequences of thyroid dysfunction.