GWAS Replication and Fine Mapping of Type 2 Diabetes Loci in an Igbo Population Cohort from Anambra and Enugu States

Genome-wide association studies have identified over 500 loci associated with type 2 diabetes (T2DM) predominantly in European and East Asian populations. The transferability of these findings to West African populations, particularly the Igbo of South East Nigeria, is uncertain due to differences in linkage disequilibrium patterns and allele frequencies. This study replicated established T2DM GWAS loci and conducted fine mapping in an Igbo population cohort from Anambra and Enugu States. Eight hundred Igbo adults (400 T2DM cases, 400 normoglycaemic controls) were recruited from tertiary hospitals and community screening events. Participants were genotyped using the H3Africa Chip, and 40 previously reported T2DM susceptibility loci were tested for replication. For confirmed loci, conditional analysis and 99 percent credible set construction were performed for fine mapping of causal variants. Fifteen of 40 tested loci showed directionally consistent associations, with seven reaching nominal significance. Fine mapping at the TCF7L2 locus identified a West African-specific credible variant set distinct from European fine-mapping results. These findings advance T2DM genetic architecture understanding in the Igbo population and provide data to support multi-ethnic GWAS meta-analyses. Keywords: GWAS replication, type 2 diabetes, Igbo population, fine mapping, TCF7L2