The TSI outperform the CEU as reference for the Greek population in 10 regions. However, there are four regions where the CEU are actually better reference samples than the TSI, contrary to what one might expect based on geographic proximity of the populations. Among them, the most notable are a region of chromosome 7 (100% coverage using the CEU as reference vs. 91.7% using the TSI as reference) and the chromosomal region around COMT (100% coverage using the CEU as reference vs. 93% coverage using the TSI as reference). The Chromosome 7 region spans the TAS2R38 gene (responsible for the PTC taster/nontaster phenotype), as well as the CLEC5A gene. The latter gene has been found to have a role in immune response and interact with dengue virus. Finally, the SLC44A5 regions (discussed in previous sections as one of the most population-differentiating regions in our study) were also captured more accurately in Greeks when the CEU were used as the reference population as opposed to the TSI.Annals of Human Genetics DOI: 10.1111/j.1469-1809.2012.00730.x
Exploring Genomic Structure Differences and Similarities between the Greek and European HapMap Populations: Implications for Association Studies
Vasileios Stathias et al.
Studies of the genomic structure of the Greek population and Southeastern Europe are limited, despite the central position of the area as a gateway for human migrations into Europe. HapMap has provided a unique tool for the analysis of human genetic variation. Europe is represented by the CEU (Northwestern Europe) and the TSI populations (Tuscan Italians from Southern Europe), which serve as reference for the design of genetic association studies. Furthermore, genetic association findings are often transferred to unstudied populations. Although initial studies support the fact that the CEU can, in general, be used as reference for the selection of tagging SNPs in European populations, this has not been extensively studied across Europe. We set out to explore the genomic structure of the Greek population (56 individuals) and compare it to the HapMap TSI and CEU populations. We studied 1112 SNPs (27 regions, 13 chromosomes). Although the HapMap European populations are, in general, a good reference for the Greek population, regions of population differentiation do exist and results should not be light-heartedly generalized. We conclude that, perhaps due to the individual evolutionary history of each genomic region, geographic proximity is not always a perfect guide for selecting a reference population for an unstudied population.