Epigenetics is implicated in the basis of gender incongruence. An epigenome-wide association analysis.

The main objective was to carry out a global DNA methylation analysis in a population with gender incongruence before gender-affirming hormone treatment (GAHT), in comparison to a cisgender population. Methods: A global CpG (cytosine-phosphate-guanine) methylation analysis was performed on blood from 16 transgender people before GAHT vs. 16 cisgender people using the Illumina© Infinium Human Methylation 850k BeadChip, after bisulfite conversion. Changes in the DNA methylome in cisgender vs. transgender populations were analyzed with the Partek® Genomics Suite program (false discovery rate correction FDR p < 0.05; fold change ≥ ±2) by a 2-way ANOVA test comparing populations by group and their sex assigned at birth. Subsequently, we added two contrast interaction terms comparing populations: cis men vs. trans people with male assigned birth sex and cis women vs. trans people with female assigned birth sex. Finally, to interpret the list of significant genes, an enrichment analysis was performed with the Partek® Pathway program and the WebGestalt.