Genetic Diversity and Markers of Symptomatic Malaria Susceptibility in Three Malaria-Endemic Regions of Cameroon

Abstract

Malaria remains a global public health problem as the current lines of treatment and control are becoming increasingly less effective or under threat of decreased efficacy. While much progress has been made towards malaria vaccine development, the enormous diversity of the parasite antigens, and redundancy in their interaction with humans pose a great challenge to the current vaccine candidates, particularly in regions with high malaria transmission. In Cameroon, malaria contributes significantly to mortality reported at healthcare facilities; a large proportion of which are children below 5 years old. Evidence for the involvement of host (human) genetic factors in increased or decreased malaria susceptibility has mounted for over the years. Large scale multi-site genome-wide association studies (GWAS) have now revealed multiple human genetic factors associated with malaria susceptibility. Yet, due to the high genetic diversity (population structure) among African populations, these methods have been limited in multi-site studies. In this study, a country-specific GWAS for malaria case and control participants from the South West, Littorale, and Centre regions in Cameroon was performed in order to uncover genetic variants that may not have been found by previous studies. First, population structure analysis was performed on 1073 samples to ascertaining whether there was significant genetic differentiation within the regions that could reduce the power of the GWAS. The study confirmed significant genetic diversity among Cameroon’s major ethnic groups; Bantu, Semi-Bantu, and Fulani. Association analysis confirmed attenuation of GWAS signals due to this population structure. In addition, markers in potentially novel malaria protective loci were uncovered; SOD2 specific to Cameroon’s Semi-Bantu ethnic group and CHST15 in Cameroon’s Bantu and Semi-Bantu ethnic groups. Furthermore, heterogeneity within the beta-like globin (HBB) gene cluster was revealed among the Bantu and Semi-Bantu ethnic groups that underscores age old fine-scale structure within the country. The findings of this study highlight population-specific variants and disparate genetic association patterns among Cameroon’s major ethnic groups that should be important for future genetic association studies in the Country. The findings also further the understanding of the evolutionary course of Cameroon’s major ethnic populations under malaria pressure