The UG2G initiative: A study of disease susceptibility in 7000 individuals from Uganda using whole genome sequencing and genotyping approaches. D. Gurdasani1, T. Carstensen1, S. Fatumo1, C. S. Franklin1, E. Wheeler1, I. Tachmazidou1, J. Huang1, A. Karabarinde2, G. Asiki2 1) Human Genetics, Wellcome Trust Sanger Institute, Cambridge, United Kingdom; 2) Medical Research Council/Uganda Virus Research Institute, Uganda.

   Given the genetic diversity in Africa, and the current lack of understanding of genetic determinants of disease susceptibility in the region, novel efforts to advance this understanding by large-scale genome wide association studies (GWAS) are essential. The UG2G (Uganda 2000 Genomes) project builds on previous initiatives to examine African genetic diversity (African Genome Variation Project), representing a substantial advance in large-scale African genomics. Its primary objectives are to 1. Examine the heritability and genetic determinants of a wide range of biomedical traits to identify novel susceptibility loci among Africans; 2. Provide a global resource for researchers, by generating the largest African reference panel for imputation to date, and a repository of information relating to genetic variation in Africa, relevant to population genetics and fine-mapping efforts; 3. Strengthen research capacity, training, and collaboration across the region; 4. Provide novel insights into population demographic history in the region; and 5. Characterise in detail de novo mutation rates and recombination patterns in Africa. This initiative comprises whole genome sequence (WGS) and dense genotype data on 2000 and 5000 individuals, respectively, from the General Population Cohort (GPC), Uganda. The GPC is an annual survey that collects detailed information on over 50 traits, including cardio-metabolic, anthropometric, haematological, liver, renal function and infectious disease traits from ~20,000 individuals across 25 villages in south-western Uganda. We carried out low coverage 4x WGS (Illumina HiSeq 2000) of 2000 individuals, representing multiple ethno-linguistic groups, in addition to dense genotyping (Illumina Omni 2.5M chip array) of 5000 individuals. For in-depth characterisation of variation, we additionally sequenced trios at high coverage (30x). Based on preliminary data, we identify a novel locus associated with HbA1C levels in the HbA2 gene on chr16 (P=6.9e-19). This 3.8kb deletion is common among Africans (MAF=0.25) and rare among Europeans (MAF=0.005), and has been previously shown to be strongly associated with several haematological traits among African-Americansconsistent with our findings from the GPC. Our findings provide proof-of-concept that in addition to providing an invaluable resource to researchers worldwide, such large-scale efforts in Africa can identify novel susceptibility loci associated with complex disease traits.

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