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The frequencies of pharmacogenetic alleles vary considerably between populations which has important implications for the impact of these alleles in different populations. However, current population grouping methods to communicate these patterns are insufficient as they are inconsistent and fail to reflect the distribution of genetic variability around the world. To facilitate and standardize the reporting of global variability in pharmacogenetic allele frequencies, we present nine broad biogeographical groups, defined by global autosomal genetic structure. These groups are based on data from large-scale initiatives, including the 1000 Genomes Project and the Human Genome Diversity Project, and reflect population genetic history, genetic distances between populations, and geographical proximity, with borders falling predominantly along national boundaries to simplify application of the grouping system. The geographically-defined groups are American, Central/South Asian, East Asian, European, Near Eastern, Oceanian, and Sub-Saharan African. Because of their distinct genetic patterns and frequent inclusion in published data, we also present two admixed groups: African American/Afro-Caribbean and Latino. Here, we characterize this population grouping system in the context of broad genomic data and present its utility for annotating pharmacogenetic studies and alleles. We recognize that broadly grouping global populations is an oversimplification of human diversity, does not capture complex social and cultural identity, and uses arbitrary geographic borders. However, this grouping method is consistent with robust population genetic patterns and meets a need of the pharmacogenetics field by enabling consistent communication of the scale of variability in global allele frequencies.

Currently, no vaccine exists for hepatitis C virus (HCV), a major pathogen thought to infect 170 million people globally. Many studies suggest that host T cell responses are critical for spontaneous resolution of disease, and preclinical studies have indicated a requirement for T cells in protection against challenge. We aimed to elicit HCV-specific T cells with the potential for protection using a recombinant adenoviral vector strategy in a phase 1 study of healthy human volunteers. Two adenoviral vectors expressing NS proteins from HCV genotype 1B were constructed based on rare serotypes [human adenovirus 6 (Ad6) and chimpanzee adenovirus 3 (ChAd3)]. Both vectors primed T cell responses against HCV proteins; these T cell responses targeted multiple proteins and were capable of recognizing heterologous strains (genotypes 1A and 3A). HCV-specific T cells consisted of both CD4(+) and CD8(+) T cell subsets; secreted interleukin-2, interferon-gamma, and tumor necrosis factor-alpha; and could be sustained for at least a year after boosting with the heterologous adenoviral vector. Studies using major histocompatibility complex peptide tetramers revealed long-lived central and effector memory pools that retained polyfunctionality and proliferative capacity. These data indicate that an adenoviral vector strategy can induce sustained T cell responses of a magnitude and quality associated with protective immunity and open the way for studies of prophylactic and therapeutic vaccines for HCV.