One of the main causes of Dupuytren Disease associated with genes inherited from Neanderthals

It is now well established that the first humans migrated in more than one wave from Africa to the Middle 

East where they encountered Neanderthals and mixed with them. For this reason, Africans who did not migrate out of Africa did not admix with Neanderthals and do not possess any Neanderthal genetic material whereas unto 2 percent of the genes of the rest of the human population can be of Neanderthal origin.

One of these inherited genes is EPDR1 that has been found by Nobel laureate Svante Pääbo and his team to be closely associated with Dupuytren Disease. Their article can be accessed below:

Major Genetic Risk Factors for Dupuytren's Disease Are Inherited From Neandertals

Richard Ågren, Snehal Patil, Xiang Zhou, FinnGen. , Kristoffer Sahlholm, Svante Pääbo, Hugo Zeberg

Author Notes

Molecular Biology and Evolution, Volume 40, Issue 6, June 2023, msad130, https://doi.org/10.1093/molbev/msad130

Published:

14 June 2023

Abstract

Dupuytren's disease is characterized by fingers becoming permanently bent in a flexed position. Whereas people of African ancestry are rarely afflicted by Dupuytren's disease, up to ∼30% of men over 60 years suffer from this condition in northern Europe. Here, we meta-analyze 3 biobanks comprising 7,871 cases and 645,880 controls and find 61 genome-wide significant variants associated with Dupuytren's disease. We show that 3 of the 61 loci harbor alleles of Neandertal origin, including the second and third most strongly associated ones (P = 6.4 × 10⁻¹³² and P = 9.2 × 10⁻⁶⁹, respectively). For the most strongly associated Neandertal variant, we identify EPDR1 as the causal gene. Dupuytren's disease is an example of how admixture with Neandertals has shaped regional differences in disease prevalence.