Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.
Journal article

Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

  • Gurdasani D William Harvey Research Institute, Queen Mary's University of London, London, UK.
  • Carstensen T Department of Medicine, University of Cambridge, Cambridge, UK.
  • Fatumo S London School of Hygiene and Tropical Medicine, London, UK; Uganda Medical Informatics Centre (UMIC), MRC/UVRI and LSHTM (Uganda Research Unit), Entebbe, Uganda; H3Africa Bioinformatics Network (H3ABioNet) Node, Center for Genomics Research and Innovation (CGRI)/National Biotechnology Development Agency CGRI/NABDA, Abuja, Nigeria.
  • Chen G Center for Research on Genomics and Global Health, National Institute of Health, Bethesda, MD, USA.
  • Franklin CS Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Prado-Martinez J Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Bouman H Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Abascal F Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Haber M Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Tachmazidou I GSK Medicines Research Centre, Gunnels Wood Road, Stevenage Hertfordshire SG1 2NY, UK.
  • Mathieson I Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Ekoru K Medical Research Council/Uganda Virus Research Institute (MRC/UVRI) and London School of Hygiene & Tropical Medicine Uganda Research Unit on AIDS, Entebbe, Uganda; Department of Medicine, University of Cambridge, Cambridge, UK.
  • DeGorter MK Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Nsubuga RN Medical Research Council/Uganda Virus Research Institute (MRC/UVRI) and London School of Hygiene & Tropical Medicine Uganda Research Unit on AIDS, Entebbe, Uganda.
  • Finan C Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Wheeler E Wellcome Sanger Institute, Hinxton, Cambridge, UK; MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
  • Chen L Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Cooper DN Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff, UK.
  • Schiffels S Department of Archaeogenetics, Max Planck Institute for the Science of Human History, Jena, Germany.
  • Chen Y Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Ritchie GRS Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Pollard MO Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Fortune MD Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Mentzer AJ The Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Garrison E Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Bergström A Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Hatzikotoulas K Wellcome Sanger Institute, Hinxton, Cambridge, UK; Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  • Adeyemo A Center for Research on Genomics and Global Health, National Institute of Health, Bethesda, MD, USA.
  • Doumatey A Center for Research on Genomics and Global Health, National Institute of Health, Bethesda, MD, USA.
  • Elding H Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Wain LV Department of Health Sciences, University of Leicester, Leicester, UK; National Institute for Health Research, Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
  • Ehret G McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1211 Genève 14, Switzerland.
  • Auer PL Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
  • Kooperberg CL Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Reiner AP Department of Epidemiology, University of Washington, Seattle, WA, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Franceschini N Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
  • Maher D Medical Research Council/Uganda Virus Research Institute (MRC/UVRI) and London School of Hygiene & Tropical Medicine Uganda Research Unit on AIDS, Entebbe, Uganda.
  • Montgomery SB Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Kadie C Microsoft Research, Redmond, CA, USA.
  • Widmer C Microsoft Research, Los Angeles, CA, USA.
  • Xue Y Wellcome Sanger Institute, Hinxton, Cambridge, UK.
  • Seeley J London School of Hygiene and Tropical Medicine, London, UK; Medical Research Council/Uganda Virus Research Institute (MRC/UVRI) and London School of Hygiene & Tropical Medicine Uganda Research Unit on AIDS, Entebbe, Uganda.
  • Asiki G Medical Research Council/Uganda Virus Research Institute (MRC/UVRI) and London School of Hygiene & Tropical Medicine Uganda Research Unit on AIDS, Entebbe, Uganda.
  • Kamali A Medical Research Council/Uganda Virus Research Institute (MRC/UVRI) and London School of Hygiene & Tropical Medicine Uganda Research Unit on AIDS, Entebbe, Uganda.
  • Young EH Wellcome Sanger Institute, Hinxton, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK.
  • Pomilla C Wellcome Sanger Institute, Hinxton, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK.
  • Soranzo N Wellcome Sanger Institute, Hinxton, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK; The National Institute for Health Research Blood and Transplant Unit (NIHR BTRU) in Donor Health and Genomics, University of Cambridge, Cambridge, UK.
  • Zeggini E Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  • Pirie F Department of Diabetes and Endocrinology, University of KwaZulu-Natal, Durban, South Africa.
  • Morris AP The Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK; Department of Biostatistics, University of Liverpool, Liverpool, UK.
  • Heckerman D Microsoft Research, Los Angeles, CA, USA.
  • Tyler-Smith C Wellcome Sanger Institute, Hinxton, Cambridge, UK. Electronic address: cts@sanger.ac.uk.
  • Motala AA Department of Diabetes and Endocrinology, University of KwaZulu-Natal, Durban, South Africa. Electronic address: motala@ukzn.ac.za.
  • Rotimi C Center for Research on Genomics and Global Health, National Institute of Health, Bethesda, MD, USA. Electronic address: rotimic@mail.nih.gov.
  • Kaleebu P London School of Hygiene and Tropical Medicine, London, UK; Uganda Medical Informatics Centre (UMIC), MRC/UVRI and LSHTM (Uganda Research Unit), Entebbe, Uganda; Medical Research Council/Uganda Virus Research Institute (MRC/UVRI) and London School of Hygiene & Tropical Medicine Uganda Research Unit on AIDS, Entebbe, Uganda. Electronic address: pontiano.kaleebu@mrcuganda.org.
  • Barroso I Wellcome Sanger Institute, Hinxton, Cambridge, UK; MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. Electronic address: ib1@sanger.ac.uk.
  • Sandhu MS Department of Medicine, University of Cambridge, Cambridge, UK. Electronic address: mss31@cam.ac.uk.
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  • 2019-11-02
Published in:
  • Cell. - 2019
English Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.
Language
  • English
Open access status
bronze
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Persistent URL
https://sonar.ch/global/documents/46835
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