Twin study: genotype-dependent epigenetic factors affecting free thyroxine levels in the normal range.

To explore the clinical application of DNA methylation affecting thyroid function, we evaluated the association of DNA methylation with free thyroxine (FT4) and TSH measurements in monozygotic twins. Discordant pairs for FT4 or TSH levels were examined for the relationship between the within-pair difference of each measurement and the DNA methylation levels using epigenome-wide association studies. The contribution of polymorphisms to the methylation sensitivity was also examined. We found two CpG sites significantly associated with FT4 levels, and also some CpG sites showing significant differences in their methylation levels within FT4-discordant pairs depending on the polymorphism in . The FT4 level may be associated with a combination of methylation and polymorphisms in the gene.