Association between <i>TG</i> Genetic Polymorphisms and Thyroid Diseases

Thyroid diseases are among the most prevalent endocrine diseases and are more common in females. A genetic association study of 104 single nucleotide polymorphisms (SNPs) within the TG gene was conducted using data from the Korean Genome and Epidemiology Study (KoGES) to identify SNPs associated with thyroid diseases. The analysis identified 28 significant SNPs, with rs2248346 (odds ratio=1.46, P=5.30×10-3) as the most significant variant. Haploview-based linkage disequilibrium (LD) analysis revealed five LD blocks, with strong genetic associations observed between blocks 2 and 3 and blocks 4 and 5. Locuszoom analysis identified rs2248346 at the 3’ end of the TG gene, showing high LD (r2≥0.8) with neighboring SNPs in a low recombination rate region. RegulomeDB analysis identified six SNPs with high regulatory potential, influencing transcription factor binding sites and chromatin accessibility. Expression quantitative trait loci analysis showed that rs2246611 (normalized effect size=-0.37, P=1.96×10-5) was linked to reduced TG expression in esophagus-gastroesophageal junction tissue. Splicing quantitative trait loci analysis identified 11 SNPs affecting RNA splicing in thyroid tissue. These findings underscore the role of TG genetic polymorphisms in the etiology of thyroid diseases in Koreans, supporting their potential as biomarkers for precision diagnostics and targeted therapies.