gms | German Medical Science

Objectives/Interrogation: Dupuytren disease (DD), a fibroproliferative disorder of the palmar fascia that causes flexion contractures in the fingers, is prevalent in people of North-Western European descent and less so in other ethnicities. DD is a complex disorder, influenced by genetic risk variants. We aimed to study if the marked differences in prevalences in DD between ethnic (sub)groups could be explained by differences in allele frequencies of the 26 known genetic risk variants of DD.

Methods: Genetic risk scores (GRS) composed of the 26 DD risk variants were calculated for the 26 populations from the 1000Genomes database and correlated to observed DD prevalences from literature. For comparison, GRSs were generated for 100 sets of 26 random SNPs and also correlated to observed DD prevalences to determine the significance of the observed correlation. To determine whether differences in allele frequencies between ethnicities were caused by natural selection, fixation indices (Fst) were calculated from the 26 SNPs and from the sets of 26 random SNPs for comparison.

Results and Conclusions: Observed prevalences could be determined from literature for ten populations. Their correlation with the GRS composed of DD SNPs proved to be 0.51 (p<0.00). The Fsts between British and other populations were low for Europeans, ad mixed American, and South-Asian populations, and moderate for East-Asians and Africans, but none of them was significantly different from expected values determined from the random sets.

The 26 known genetic risk variants associated with DD explain for a substantial part (R2=0.26) the differing DD prevalences observed between ethnicities.