SummaryThroughout biomedical research, there is growing interest in the use of ancestry informative markers (AIMs) to deconstruct racial categories into useful variables. Studies on recently admixed populations have shown significant population substructure due to differences in individual ancestry; however, few studies have examined Caribbean populations. Here we used a panel of 28 AIMs to examine the genetic ancestry of 298 individuals of African descent from the Caribbean islands of Jamaica, St. Thomas and Barbados. Differences in global admixture were observed, with Barbados having the highest level of West African ancestry (89.6% ± 2.0) and the lowest levels of European (10.2% ± 2.2) and Native American ancestry (0.2% ± 2.0), while Jamaica possessed the highest levels of European (12.4% ± 3.5) and Native American ancestry (3.2% ± 3.1). St. Thomas, USVI had ancestry levels quite similar to African Americans in continental U.S. (86.8% ± 2.2 West African, 10.6% ± 2.3 European, and 2.6% ± 2.1 Native American). Significant substructure was observed in the islands of Jamaica and St. Thomas but not Barbados (K=1), indicating that differences in population substructure exist across these three Caribbean islands. These differences likely stem from diverse colonial and historical experiences, and subsequent evolutionary processes. Most importantly, these differences may have significant ramifications for case-control studies of complex disease in Caribbean populations.

BACKGROUND Multiple genetic studies have confirmed associations of 8q24 variants with susceptibility to prostate cancer (CaP). However, the magnitude of risk conferred in men living in west Africa is unknown. METHODS Here we determine the prevalence of 8q24 risk alleles and test for association with CaP risk alleles in west African descent populations from rural Nigeria, Cameroon, and the Caribbean island of Jamaica. Ten 8q24 SNPs were genotyped in histologically-confirmed CaP cases (n=308) and clinically evaluated controls (n=469). In addition, unrelated individuals from Sierra Leone (n=380) were genotyped for comparison of allele frequency comparisons. RESULTS SNPs rs6983561, rs7008482, and rs16901979 were significantly associated with CaP risk in west Africans (P<0.03). No associations with CaP were observed in our Caribbean samples. Risk alleles for rs6983267, rs7008482, and rs7000448 were highly prevalent (>84%) in West Africa. We also reveal that the A-risk allele for the ‘African-specific’ SNP bd11934905 was not observed in 1,886 chromosomes from three west African ethnic groups suggesting that this allele may not be common across west Africa, but is geographically restricted to specific ethnic group(s). CONCLUSIONS We provide evidence of association of 8q24 SNPs with prostate cancer risk in men from Nigeria and Cameroon. Our study is the first to reveal genetic risk due to 8q24 variants (in particular, region 2) with CaP within two west Africa countries. Most importantly, in light of the disparate burden of CaP in African Americans, our findings support the need for larger genetic studies in west African descent populations to validate and discern function of susceptibility loci in the 8q24 region.

Our data indicate that CDH1 likely is a low-penetrant PCA susceptibility gene, however, population differences in linkage disequilibrium within the CDH1 gene region may influence the effect of susceptibility alleles such as -160A.