Evaluation of Genome Wide Association Study Associated Type 2 XXXX Susceptibility Loci in Sub Saharan Africans.

@entity2175 @entity8405 @entity6 @entity8406
UNASSIGNED: Genome wide association studies (GWAS) for @entity2175 ( @entity2175 ) undertaken in European and Asian ancestry populations have yielded dozens of robustly associated loci. However, the genomics of @entity2175 remains largely understudied in sub-Saharan Africa (SSA), where rates of @entity2175 are increasing dramatically and where the environmental background is quite different than in these previous studies. Here, we evaluate 106 reported @entity2175 GWAS loci in continental Africans. We tested each of these SNPs, and SNPs in linkage disequilibrium (LD) with these index SNPs, for an association with @entity2175 in order to assess transferability and to fine map the loci leveraging the generally reduced LD of African genomes. The study included 1775 unrelated Africans (1035 @entity2175 cases, 740 controls; mean age 54 years; 59% female) enrolled in Nigeria, Ghana, and Kenya as part of the Africa America @entity6 (AADM) study. All samples were genotyped on the Affymetrix Axiom PanAFR SNP array. Forty-one of the tested loci showed transferability to this African sample (p < 0.05, same direction of effect), 11 at the exact reported SNP and 30 others at SNPs in LD with the reported SNP (after adjustment for the number of tested SNPs). @entity8405 SNP @entity8406 was the most significant locus in this study (p = 1.61 * 10(-8)). Most of the loci that showed transferability were successfully fine-mapped, i.e., localized to smaller haplotypes than in the original reports. The findings indicate that the genetic architecture of @entity2175 in SSA is characterized by several risk loci shared with non-African ancestral populations and that data from African populations may facilitate fine mapping of risk loci. The study provides an important resource for meta-analysis of African ancestry populations and transferability of novel loci.
