Published in Sexual Medicine, this study employs whole exome sequencing (WES) to identify genetic susceptibility loci in transgender individuals, a step toward the molecular characterization of the biological basis of gender dysphoria.
Exome sequencing allows analyzing the coding regions of the genome, where most variants with known functional impact are concentrated. The authors applied this technique to a cohort of transgender individuals and compared rare and common variants with control panels, prioritizing genes involved in sexual differentiation, steroid signaling and brain development.
The analysis identified candidate variants in genes associated with the estrogen and androgen receptor pathway, as well as in genes involved in neurogenesis and synaptic plasticity. Although the results are exploratory in nature and must be validated in larger cohorts, they offer a preliminary map of genomic regions of interest.
The authors discuss the limitations inherent to genetic association studies in populations of reduced size, as well as the importance of independent replication before drawing clinical conclusions. They also emphasize the need for multi-omic approaches that integrate genetics, epigenetics and neuroimaging.
This work contributes to the growing evidence that gender incongruence has a polygenic genetic component, and marks concrete directions for future genome-wide association studies in transgender individuals.
Bibliographic reference
Liu N, et al. Whole exome sequencing analysis of susceptibility loci in transgender individuals. Sex Med. 2025;13(4):qfaf062.
DOI: https://doi.org/10.1093/sexmed/qfaf062
PMID: 40861848
Publication access: the original reference can be consulted in open access or through the indicated DOI.
