Research

The HEDGE study

The Hypermobile Ehlers-Danlos Genetic Evaluation (HEDGE) study was initiated by The Ehlers-Danlos Society to examine the genes of over 1000 particpants around the world who have hEDS or HSD (Hypermobility Spectrum Disorder). It is the most extensive study involving over 85 counties with an aim to find a genetic cause of hESD.

An October 2025 Update included the following findings:

  • The MTHFR mutation did not prove to be linked to hEDS.
  • TXNB variants were found to increase the risk for hEDS 3-5x compared to the general population; however this accounted for only 1% of participants.
  • The recently linked KLK15 variants were shown to be just as common in the participants as controls; however, it could still lead to symptoms in some people.

https://www.ehlers-danlos.com/the-hedge-study/

Results from GWS Study with The Norris Lab

The Norris Lab, located in Charleston, SC, is a research lab that frequently hosts interns who have lived experience with disabling conditions and collaborate to gain perspective and advancements in the areas of Ehlers-Danlos Syndrome (EDS) and cardiovascular disease. Two recently discovered genes show promise for their relation to hEDS:

  • Two gene variants in the ACKR3 (chromosome 2) region and SLC39A13 gene were shown to be significant in relation to hEDS.
  • The ACKR3 gene is located on the tibial nerve, which has been shown to affect neuroimmune and pain signaling pathways. This correlates to symptoms those with EDS experience, such as pain throughout the body and brain fog. Much of the time, brain fog is actually inflammation in the brain.
  • The SLC39A13 gene is a zinc transporter that is critical in the development of connective tissue, so one could see how that could be a cause of EDS, as well.

Petrucci-Nelson, T., Guilhaumou, S., Berrandou, T.E., Gensemer, C., Georges, A., Huff, M., Fustier, M.A., Esmael, A., Henry, J., Jaye, O., Phookan, R., Dooley, S., Byerly, K., Loizzi, B., Fenner, R., Mach, E., Weintraub, A., Daylor, V., Weninger, J., … Norris, R.A. (2025). Complex Genetics and Regulatory Drivers of Hypermobile Ehlers-Danlos Syndrome: Insights from Genome-Wide Association Study Meta-analysis. medRxiv [Preprint]. https://doi.org/10.1101/2025.09.19.25336146.