For the remaining loci, variable replication among ethnicities likely occurred for one or more of the following reasons. First, individual genetic variants contributing to complex traits have very modest effect sizes. Therefore, each individual ethnic group may have been underpowered to detect an association. This problem could be addressed by genotyping the polymorphisms in additional individuals of African-American or Hispanic ancestry. Second, the locus discovered in whites may be relevant in other ethnicities but the specific polymorphisms associated with lipids may differ across ethnicities. Older populations such as those of African descent have a more complex linkage disequilibrium (LD) structure.19 Therefore, if the causal variant in African Americans is poorly correlated with the index SNP discovered from whites, no association will be detected. In this case, testing a comprehensive set of variants that tag the entire locus (i.e. fine-mapping the region in other ethnicities) would be required to detect the relevant polymorphism(s). Finally, genetic variants in different ethnicities may lie in regions of the genome distinct from those observed in whites. New variant discovery through additional GWA studies or resequencing efforts in other ethnicities would be necessary to locate these variants. Such efforts are currently underway.
