An epigenome-wide association study (EWAS) published in Frontiers in Neuroscience by the group of Rosa Fernández, Eduardo Pásaro and Antonio Guillamón shows that people with gender incongruence present globally different DNA methylation profiles before starting any hormonal treatment.
Using the genome-wide methylation array, the researchers compared cytosine-guanine (CpG) methylation profiles in a population with gender incongruence versus cisgender controls. The main finding is that there are systematic differences in global methylation that precede gender-affirming hormonal treatment.
These results are relevant because DNA methylation is one of the key epigenetic mechanisms in the sexual differentiation of the brain. Previous studies in animal models have shown that inhibiting methylation during brain development alters sexually dimorphic neurobehavioral phenotypes in adult life.
The authors interpret the methylation differences as evidence that epigenetic regulation participates in the biological substrate of gender incongruence, potentially acting as an intermediary between the genetic endowment and environmental and hormonal factors.
This work stands as a central piece of the research line of the Spanish group on the biological basis of gender identity, and underscores the need for longitudinal studies that analyze the evolution of methylation throughout hormonal therapy.
Bibliographic reference
Ramírez K, et al. Epigenetics Is Implicated in the Basis of Gender Incongruence: An Epigenome-Wide Association Analysis. Front Neurosci. 2021;15:701017.
DOI: https://doi.org/10.3389/fnins.2021.701017
PMID: 34566757
Publication consultation: the original reference can be consulted in open access or through the indicated DOI.
