Modification of TSH-related genetic effects by indicators of socioeconomic position.

Objective: Thyroid-stimulating hormone (TSH) is influenced by genetic and environmental factors such as socioeconomic position (SEP). However, interactions between TSH-related genetic factors and indicators of SEP have not been investigated to date. The aim of the study was to determine whether education and income as SEP indicators may interact with TSH-related genetic effect allele sum scores (GESTSH_2013 and GESTSH_2020) based on two different GWAS meta-analyses that affect TSH values in a population-based study. Methods: In 4085 participants of the Heinz Nixdorf Recall Study associations between SEP indicators, GESTSH and TSH were quantified using sex- and age-adjusted linear regression models. Interactions between SEP indicators and GESTSH were assessed by GESTSH × SEP interaction terms, single reference joint effects and calculating genetic effects stratified by SEP group. Results: Participants within the highest education group showed the strongest genetic effect with on average 1.109-fold (95% CI: 1.067-1.155) higher TSH values per GESTSH_2013 SD, while in the lowest education group, the genetic effect was less strong (1.061-fold (95% CI: 1.022-1.103)). In linear regression models including interaction terms, some weak indication for a positive GESTSH_2013 by education interaction was observed showing an interaction effect size estimate of 1.005 (95% CI: 1.000-1.010) per year of education and GESTSH_2013 SD. No indication for interaction was observed for using income as SEP indicator. Using the GESTSH_2020, similar results were observed. Conclusion: Our results gave some indication that education may affect the expression of TSH-related genetic effects. Stronger genetic effects in high-education groups may be explained by environmental factors that have an impact on gene expression and are more prevalent in high SEP groups.

TSH concentrations in parents and their offspring: a cross-sectional family-based analysis.

OBJECTIVE: Studies that evaluated the genetic influences on thyroid-stimulating hormone (TSH) concentrations were primarily performed in twin cohorts. The aim of this study was to investigate the sex-specific association of serum TSH concentrations between parents and their offspring. METHODS: We used data from the population-based Heinz Nixdorf Recall Study and the associated MultiGeneration Study, including offspring and their biological parents. In 3115 participants (including 1558 offspring from 1138 families), self-reported thyroid diseases and median TSH concentrations depending on thyroid status were assessed. Familial associations of TSH concentrations were investigated in 1485 healthy subjects using linear regression modeling in each group of the parent-offspring relationship using the parent's TSH concentration as the exposure of interest. To account for the family effect, a mixed-effects ordinal logistic regression model with random intercept varying at the family level was fitted, using the TSH concentration of the offspring classified into sex- and age-specific quartiles as the outcome. RESULTS: For every 1 mIU/L increase in the mother's or father's TSH concentration, the daughter's TSH concentration increases by 0.13 mIU/L (95% CI: -0.01; 0.27) and 0.19 mIU/L (0.05; 0.33), respectively, and the son's TSH concentration increases by 0.13 mIU/L (0.02; 0.25) and 0.20 mIU/L (0.08; 0.32), respectively. Further sensitivity analyses by expanding inclusion criteria and taking family clustering into account corroborated these results. CONCLUSIONS: Serum TSH concentrations of parents are positively associated with those of their offspring in all sex-specific relationships.