Immunogenomic Basis of Differential Susceptibility to Severe Plasmodium falciparum Malaria in Children from Hausa and Yoruba Ethnic Groups in Nigeria

Population differences in susceptibility to severe Plasmodium falciparum malaria may be influenced by immunogenetic variants, and comparative immunogenomic analysis between ethnically distinct Nigerian populations offers an opportunity to identify protective genetic signatures. This doctoral study investigated the immunogenomic basis of differential susceptibility to severe falciparum malaria in children from Hausa (Kano State) and Yoruba (Ogun State) ethnic backgrounds, populations with distinct ancestral genetic histories and divergent malaria transmission exposures. A case-control design enrolled 320 severe malaria cases and 320 healthy controls from each ethnic group (total n = 1,280). Whole exome sequencing was performed, and population-stratified genome-wide association analysis was conducted using PLINK and GEMMA. Candidate immune gene loci including HbS, G6PD, HLA class I and II, IL-4 promoter variants, and FcGamma receptor polymorphisms were analysed. HbAS heterozygosity conferred significant protection in both groups (OR 0.31 Hausa, OR 0.28 Yoruba). HLA-B*53:01 was significantly enriched in Yoruba controls (p = 1.4 x 10-7), consistent with prior East African protective associations. A novel non-synonymous variant in IL-10 regulatory sequence was identified as significantly associated with severe malaria protection exclusively in the Hausa cohort (OR 0.44, p = 2.1 x 10-6). Population-stratified protective variants suggest ethnicity-informed vaccine adjuvant strategies and provide an original immunogenomic contribution to the Nigerian malaria genetics literature. Keywords: immunogenomics, severe malaria, population genetics, HLA, Nigeria.