Ancient DNA study provides clues to leprosy susceptibility in medieval Europe

Abstract

Background 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, a case-control association analysis between multiple human leukocyte antigen (HLA) alleles and leprosy was performed in a medieval European population for the first time. The sample comprised 293 medieval individuals from 18 archaeological sites in Denmark (N = 16) and Germany (N = 2). Results Our results indicate that HLA-B*38 was associated with leprosy risk. Furthermore, we detected three novel variants that were possibly involved in leprosy susceptibility (HLA-A*23, DRB1*13 and DPB1*452). Interestingly, we noted a subtle temporal change in frequency for several alleles previously associated with infectious diseases, inflammatory disorders and cancer in present-day populations. Conclusions 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.