Understanding the genetic and environmental factors influencing phenotypes is central to improving human health. However, most studies of genetic architecture involve populations living in the United States, Europe and Asia. Though large, these population samples capture only a tiny subset of the standing genetic and phenotypic variation in humans. Africa on the other hand contains tremendous phenotypic, cultural, linguistic, genetic and environmental diversity and is the source of the worldwide range expansion of all modern humans in the past 100,000 years. In fact, African populations show levels of genetic diversity and substructure equivalent to that seen at the global level. Some of these observed differences are thought to reflect local adaptation to the distinct diets, climates and exposure to pathogens experienced by each group. The broad objective of this study is to incorporate genetic and phenotypic information from Africa into the emerging picture of the genetics of health related traits. We propose to analyze a unique dataset assembled by the Tishkoff lab that includes both DNA and phenotypic measurements for as many as 3324 individuals (depending on the trait) across 61 highly diverse African ethnic groups, a subset of which will be genotyped on the lllumnia 1M SNP chip. We will first characterize the standing phenotypic variation in the data and identify groups of populations showing highly contrasting phenotypes that will be especially informative in further genetic analyses. Traits to be analyzed include: adult height, weight, body mass index (BMI), blood glucose level, resting blood pressure, resting heart rate, taste perception (PTC, Salicin and SOA) and lactase persistence. Second, using dense SNP marker data for a highly diverse subset of our sampled individuals, we will identify areas of the genome showing signatures of natural selection. Such genomic regions may harbor loci involved in adaptations to diet including altered carbohydrate, protein and lipid metabolism, to physical environmental factors including growth rate and body composition, and to infectious disease susceptibility including modified immune system function. Finally, using the same densely genotyped individuals we will directly explore genotype-phenotype relationships for our traits of interest focusing on known candidate genes/SNPs and regions showing evidence of natural selection.
