Causal effects of thyroid volume change on thyroid disease: a Mendelian randomization study

Abstract

Background: Observational studies have suggested an association between thyroid volume changes and thyroid disease, but the causal relationship and direction of these effects remain unclear. This study employs a two-sample Mendelian randomization (MR) approach to assess the effect of thyroid volume on clinically common benign and malignant thyroid diseases. Methods: Summary data from genome-wide association studies (GWAS) were utilized for secondary data analysis to investigate the link between thyroid volume and disease. Gene loci strongly associated with thyroid volume were selected as the instrumental variables. Five complementary two-sample MR methods were used to evaluate the causal effect of thyroid volume on thyroid diseases and thyroid stimulating hormone (TSH). Results: Thyroid volume was found to be significantly associated with autoimmune thyroid disease [odds ratio (OR) =1.045; 95% confidence interval (CI): 1.022–1.069; P<0.001], Hashimoto’s thyroiditis (OR =1.800; 95% CI: 1.167–2.778; P=0.008), Graves’ disease (OR =0.136; 95% CI: 0.065–0.282; P<0.001), hyperthyroidism (OR =1.011; 95% CI: 1.008–1.014; P<0.001), multinodular goiters (OR =121.541; 95% CI: 23.323–633.378; P<0.001), non-toxic single thyroid nodules (OR =7.536; 95% CI: 2.280–24.911; P<0.001), benign thyroid neoplasms (OR =4.300; 95% CI: 1.170–15.802; P=0.03), and TSH levels (OR =0.401; 95% CI: 0.247–0.652; P<0.001). Thyroid volume was negatively associated with thyroid carcinomas (OR =0.401; 95% CI: 0.208–0.772; P=0.006; β =−0.915). Conclusions: Our study found that there is a causal relationship between thyroid volume and some thyroid diseases, and that increased thyroid volume levels exert protective effects on thyroid carcinoma. Monitoring thyroid volume may be of value in the prevention of clinical thyroid diseases.