# Ancient DNA study provides clues to leprosy susceptibility in medieval Europe

## TL;DR

Ancient DNA analysis reveals genetic factors linked to leprosy susceptibility in medieval Europe, offering insights into the disease's decline.

## Contribution

The study identifies novel HLA alleles associated with leprosy risk in medieval populations using ancient DNA.

## Key findings

- HLA-B*38 is associated with leprosy risk in medieval Europe.
- Three novel HLA variants (HLA-A*23, DRB1*04, DRB1*13) may influence leprosy susceptibility.
- Temporal shifts in HLA allele frequencies suggest historical disease impacts on European genetics.

## Abstract

Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) that reached an epidemic scale in the Middle Ages. Nowadays, the disease is absent in Europe and host genetic influences have been considered as a contributing factor to leprosy disappearance. In this study, we perform a case–control association analysis between multiple human leukocyte antigen (HLA) alleles and leprosy in a medieval European population. The sample comprises 302 individuals from 18 archaeological sites in Denmark (N = 16) and Germany (N = 2).

Our results indicate that HLA-B*38 is associated with leprosy risk. Furthermore, we detect three novel variants that were possibly involved in leprosy risk or protection: HLA-A*23, DRB1*04, and DRB1*13. We also note a subtle temporal change in frequency for several alleles previously associated with infectious diseases, inflammatory disorders, and cancer in present-day populations.

This study demonstrates the potential of ancient DNA in the identification of genetic variants involved in predisposition to diseases that are no longer present in Europe but remain endemic elsewhere. Although it is difficult to pinpoint the reason behind the temporal frequency shift, past epidemics of infectious diseases have likely influenced the HLA pool in present-day Europe.

The online version contains supplementary material available at 10.1186/s13059-025-03925-8.