DNA methylation at a nutritionally sensitive region of the gene is associated with thyroid volume and function in Gambian children.

PAX8 is a key thyroid transcription factor implicated in thyroid gland differentiation and function, and gene methylation is reported to be sensitive to the periconceptional environment. Using a novel recall-by-epigenotype study in Gambian children, we found that hypomethylation at age 2 years is associated with a 21% increase in thyroid volume and an increase in free thyroxine (T4) at 5 to 8 years, the latter equivalent to 8.4% of the normal range. Free T4 was associated with a decrease in DXA-derived body fat and bone mineral density. Furthermore, offspring methylation was associated with periconceptional maternal nutrition, and methylation variability was influenced by genotype, suggesting that sensitivity to environmental exposures may be under partial genetic control. Together, our results demonstrate a possible link between early environment, gene methylation and thyroid gland development and function, with potential implications for early embryonic programming of thyroid-related health and disease.