Browsing by Author "Nyanjom, S.G."
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Item Fine scale human genetic structure in three regions of Cameroon reveals episodic diversifying selection(nature research /scientific reports, 2021) Esoh, K.K.; Apinjoh, T.O.; Nyanjom, S.G.; Wonkam, A.; Chimusa, E.R.; Amenga‑Etego, L.; Amambua‑Ngwa, A.; Achidi, E.A.Inferences from genetic association studies rely largely on the defnition and description of the underlying populations that highlight their genetic similarities and diferences. The clustering of human populations into subgroups (population structure) can signifcantly confound disease associations. This study investigated the fne-scale genetic structure within Cameroon that may underlie disparities observed with Cameroonian ethnicities in malaria genome-wide association studies in sub-Saharan Africa. Genotype data of 1073 individuals from three regions and three ethnic groups in Cameroon were analyzed using measures of genetic proximity to ascertain fne-scale genetic structure. Model-based clustering revealed distinct ancestral proportions among the Bantu, Semi Bantu and Foulbe ethnic groups, while haplotype-based coancestry estimation revealed possible longstanding and ongoing sympatric diferentiation among individuals of the Foulbe ethnic group, and their Bantu and Semi-Bantu counterparts. A genome scan found strong selection signatures in the HLA gene region, confrming longstanding knowledge of natural selection on this genomic region in African populations following immense disease pressure. Signatures of selection were also observed in the HBB gene cluster, a genomic region known to be under strong balancing selection in sub-Saharan Africa due to its co-evolution with malaria. This study further supports the role of evolution in shaping genomes of Cameroonian populations and reveals fne-scale hierarchical structure among and within Cameroonian ethnicities that may impact genetic association studies in the country.Item Genome-wide association study identifies novel candidate malaria resistance genes in Cameroon(Human Molecular Genetics, 2023) Esoh, K.K.; Apinjoh, T.O.; Amambua-Ngwa, A; Nyanjom, S.G.; Amenga-Etego, L.; Wonkam, A.; Achidi, E.A.Recent data suggest that only a small fraction of severe malaria heritability is explained by the totality of genetic markers discovered so far. The extensive genetic diversity within African populations means that significant associations are likely to be found in Africa. In their series of multi-site genome-wide association studies (GWAS) across sub-Saharan Africa, the Malaria Genomic Epidemiology Network (MalariaGEN) observed specific limitations and encouraged country-specific analyses. Here, we present findings of a GWAS of Cameroonian participants that contributed to MalariaGEN projects (n = 1103). We identified protective associations at polymorphisms within the enhancer region of CHST15 [Benjamin–Hochberg false discovery rate (FDR) < 0.02] that are specific to populations of African ancestry, and that tag strong eQTLs of CHST15 in hepatic cells. In-silico functional analysis revealed a signature of epigenetic regulation of CHST15 that is preserved in populations in historically malaria endemic regions, with haplotype analysis revealing a haplotype that is specific to these populations. Association analysis by ethnolinguistic group identified protective associations within SOD2 (FDR < 0.04), a gene previously shown to be significantly induced in pre-asymptomatic malaria patients from Cameroon. Haplotype analysis revealed substantial heterogeneity within the beta-like globin (HBB) gene cluster amongst the major ethnic groups in Cameroon confirming differential malaria pressure and underscoring age-old fine-scale genetic structure within the country. Our findings revealed novel insights in the evolutionary genetics of populations living in Cameroon under malaria pressure with new significant protective loci (CHST15 and SOD2) and emphasized the significant attenuation of genetic association signals by fine-scale genetic structure.