Twin study: genotype-dependent epigenetic factors associated with HbA1c levels

Within-pair methylation comparisons revealed several suggestive CpG sites associated with HbA1c variation. GWAS revealed one suggestive SNV associated with higher HbA1c and three SNVs potentially associated with susceptibility to HbA1c variation. Genotype-stratified analyses showed exploratory genetic background–dependent methylation changes at CpG sites, some of which correlated with gene expression.</p> <p>This study estimated the heritability of adjusted HbA1c and revealed preliminary genetic and epigenetic signals in Japanese twins.

Further studies are needed to confirm their biological and clinical significance.</p> <p>HbA1c is a blood marker that reflects average blood sugar levels over the past few months. Doctors use it to diagnose and monitor diabetes. Earlier twin studies showed that genes strongly influence HbA1c levels, but scientists do not fully understand how non-genetic factors, such as chemical changes to DNA called methylation, might also play a role.We studied 285 identical (genetically matched) and 27 non-identical Japanese twin pairs.

We measured their genetic makeup, DNA methylation patterns, and gene activity, then compared these measurements with their HbA1c levels. Our analysis estimated that genetic factors account for about 68% of the differences in HbA1c levels among adults, after adjusting for lifestyle factors. We also found several DNA methylation sites and genetic variants that may be associated with HbA1c differences between twins.

However, none of these associations reached the strict statistical thresholds normally required to confirm a genome-wide finding. We therefore describe them as candidate, or suggestive, factors rather than confirmed ones. These early findings offer clues about how genes and epigenetic changes might jointly influence blood sugar regulation.

They are not yet strong enough to guide clinical decisions. Larger studies will be needed to test whether these candidate genetic and epigenetic factors are real and whether they could eventually help personalize diabetes prevention or care.</p>