Signatures of Malaria-Driven Epistatic Selection Between the Duffy and G6PD Loci in the Colombian Pacific

The malaria hypothesis proposes that in areas with a high incidence of malaria transmission, there is likely to be a high prevalence of genetic variants that confer protection against the disease. These resistance variants, located at different loci, may be statistically associated, leading to a non-random alteration in allele frequencies and exhibiting fitness levels that are not independent across loci (epistatic interaction). The aim of this study was to investigate whether signatures of epistatic selection exist between the Duffy and G6PD loci and to estimate the adaptive values associated with their genotype combinations in the population of Buenaventura, a malaria-endemic region of the Colombian Pacific. To achieve this, the indices DST2, DIS2, D’IS2, and D’ST2 were calculated to partition the variance of linkage disequilibrium (LD) between pairs of loci, using the OhtaDstats package in R software. Additionally, fitness values and selection coefficients were estimated for the genotypic combinations of these variants. To our knowledge, this study provides the first evidence of epistatic selection between the Duffy and G6PD loci in a malaria-endemic population from the Colombian Pacific, an interaction not previously reported in the literature using a linkage disequilibrium-based approach. This finding is supported by the calculated indices, as well as by the higher fitness values observed in genotype combinations involving these resistance variants. The observed interaction may reflect complementary protection against different Plasmodium species and the absence of physiological antagonism between the two resistance mechanisms.