Roles of External Factors and Polygenic Susceptibility in Thyroid Nodules and Goiter Among Children Aged 8-10 Years in Iodine-adequate Areas of Northern China.

Thyroid nodules and goiter remain common conditions affecting healthy child development, attributable to diagnostic advances and environmental-genetic interactions. However, pediatric etiology research remains limited. A total of 997 children aged 8 to 10 years were recruited from iodine-adequate areas across 13 districts in Tianjin, China. Venous blood was collected for genotyping three single nucleotide polymorphisms (thyroid stimulating hormone receptor (TSHR) rs2268458, thyroid transcription factor 1 (TTF1) rs2076735 and phosphodiesterase 8B (PDE8B) rs4704397) using Sequenom MassARRAY. Data on up to 30 potential external factors were also collected. The detection rates of thyroid nodules and goiter were 23.57% and 8.83%, respectively. Gender, higher body surface area (BSA) (Q4: >1.30 m2), and living in a multistory building increased thyroid nodules risk (P < 0.05). Older children had higher goiter risk (P = 0.001), whereas higher BSA (Q3: 1.18-1.30 m2; Q4: >1.30 m2) and mothers with stable jobs reduced goiter risk (P < 0.05). In genotype-stratified analyses, TSHR, TTF1, and PDE8B polymorphisms appeared to moderate associations between multiple external factors (gender, BSA, urinary iodine, stress, anxiety) and thyroid nodules or goiter (P < 0.05), although no significant gene-environment interactions were detected in the overall models. Notably, among children with specific genotypes, certain factors that were not statistically significant in the full multivariable model, including urinary iodine with thyroid nodules and stress and anxiety with goiter, showed substantially strengthened associations. Multiple external factors are associated with thyroid nodules and goiter in children. Polymorphisms in TSHR rs2268458, TTF1 rs2076735, and PDE8B rs4704397 may modulate the effects of various external factors on childhood thyroid nodules and goiter.