title: The African Genome Variation Project shapes medical genetics in Africa.
abstract: Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.
authors.affiliation: 1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK.
authors.forename: Deepti
authors.initials: D
authors.lastname: Gurdasani
authors.affiliation: 1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK.
authors.forename: Tommy
authors.initials: T
authors.lastname: Carstensen
authors.affiliation: Centre for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive, MSC 5635, Bethesda, Maryland 20891-5635, USA.
authors.forename: Fasil
authors.initials: F
authors.lastname: Tekola-Ayele
authors.affiliation: 1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Department of Biological, Geological and Environmental Sciences, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Pagani
authors.affiliation: Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Tachmazidou
authors.affiliation: Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Hatzikotoulas
authors.affiliation: 1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK.
authors.forename: Savita
authors.initials: S
authors.lastname: Karthikeyan
authors.affiliation: 1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK [3] Department of Archaeology, University of York, King's Manor, York YO1 7EP, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Iles
authors.affiliation: Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Pollard
authors.affiliation: Sydney Brenner Institute of Molecular Bioscience (SBIMB), University of the Witwatersrand, The Mount, 9 Jubilee Road, Parktown 2193, Johannesburg, Gauteng, South Africa.
authors.forename: Ananyo
authors.initials: A
authors.lastname: Choudhury
authors.affiliation: 1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Vertebrate Genomics, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: Graham R S
authors.initials: GR
authors.lastname: Ritchie
authors.affiliation: Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Yali
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Asimit
authors.affiliation: Medical Research Council/Uganda Virus Research Institute, Plot 51-57 Nakiwogo Road, Uganda.
authors.forename: Rebecca N
authors.initials: RN
authors.lastname: Nsubuga
authors.affiliation: 1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Young
authors.affiliation: 1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Pomilla
authors.affiliation: Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Katja
authors.initials: K
authors.lastname: Kivinen
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.
authors.forename: Kirk
authors.initials: K
authors.lastname: Rockett
authors.affiliation: Medical Research Council/Uganda Virus Research Institute, Plot 51-57 Nakiwogo Road, Uganda.
authors.forename: Anatoli
authors.initials: A
authors.lastname: Kamali
authors.affiliation: Centre for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive, MSC 5635, Bethesda, Maryland 20891-5635, USA.
authors.forename: Ayo P
authors.initials: AP
authors.lastname: Doumatey
authors.affiliation: Medical Research Council/Uganda Virus Research Institute, Plot 51-57 Nakiwogo Road, Uganda.
authors.forename: Gershim
authors.initials: G
authors.lastname: Asiki
authors.affiliation: Medical Research Council/Uganda Virus Research Institute, Plot 51-57 Nakiwogo Road, Uganda.
authors.forename: Janet
authors.initials: J
authors.lastname: Seeley
authors.affiliation: Medical Research Council Unit, Atlantic Boulevard, SerrekundaPO Box 273, Banjul, The Gambia.
authors.forename: Fatoumatta
authors.initials: F
authors.lastname: Sisay-Joof
authors.affiliation: Medical Research Council Unit, Atlantic Boulevard, SerrekundaPO Box 273, Banjul, The Gambia.
authors.forename: Muminatou
authors.initials: M
authors.lastname: Jallow
authors.affiliation: 1] Medical Research Council/Wits Rural Public Health and Health Transitions Unit, School of Public Health, Education Campus, 27 St Andrew's Road, Parktown 2192, Johannesburg, Gauteng, South Africa [2] INDEPTH Network, 38/40 Mensah Wood Street, East Legon, PO Box KD 213, Kanda, Accra, Ghana.
authors.forename: Stephen
authors.initials: S
authors.lastname: Tollman
authors.affiliation: Institute of Biotechnology, Addis Ababa University, Entoto Avenue, Arat Kilo, 16087 Addis Ababa, Ethiopia.
authors.forename: Ephrem
authors.initials: E
authors.lastname: Mekonnen
authors.affiliation: Department of Genetics Evolution and Environment, University College, London, Gower Street, London WC1E 6BT, UK.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Ekong
authors.affiliation: University of Haramaya, Department of Biology, PO Box 138, Dire Dawa, Ethiopia.
authors.forename: Tamiru
authors.initials: T
authors.lastname: Oljira
authors.affiliation: Henry Stewart Group, 28/30 Little Russell Street, London WC1A 2HN, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Bradman
authors.affiliation: Medical Research Council Unit, Atlantic Boulevard, SerrekundaPO Box 273, Banjul, The Gambia.
authors.forename: Kalifa
authors.initials: K
authors.lastname: Bojang
authors.affiliation: 1] Sydney Brenner Institute of Molecular Bioscience (SBIMB), University of the Witwatersrand, The Mount, 9 Jubilee Road, Parktown 2193, Johannesburg, Gauteng, South Africa [2] Division of Human Genetics, National Health Laboratory Service, C/O Hospital and de Korte Streets, Braamfontein 2000, Johannesburg, South Africa [3] School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Braamfontein 2000, Johannesburg, South Africa.
authors.forename: Michele
authors.initials: M
authors.lastname: Ramsay
authors.affiliation: Centre for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive, MSC 5635, Bethesda, Maryland 20891-5635, USA.
authors.forename: Adebowale
authors.initials: A
authors.lastname: Adeyemo
authors.affiliation: Department of Microbial, Cellular and Molecular Biology, College of Natural Sciences, Arat Kilo Campus, Addis Ababa University, PO Box 1176, Addis Ababa, Ethiopia.
authors.forename: Endashaw
authors.initials: E
authors.lastname: Bekele
authors.affiliation: Department of Diabetes and Endocrinology, University of KwaZulu-Natal, 719 Umbilo Road, Congella, Durban 4013, South Africa.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Motala
authors.affiliation: Department of Paediatrics, University of Witwatersrand, 7 York Road, Parktown 2198, Johannesburg, Gauteng, South Africa.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Norris
authors.affiliation: Department of Diabetes and Endocrinology, University of KwaZulu-Natal, 719 Umbilo Road, Congella, Durban 4013, South Africa.
authors.forename: Fraser
authors.initials: F
authors.lastname: Pirie
authors.affiliation: Medical Research Council/Uganda Virus Research Institute, Plot 51-57 Nakiwogo Road, Uganda.
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
authors.affiliation: 1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.
authors.forename: Dominic
authors.initials: D
authors.lastname: Kwiatkowski
authors.affiliation: Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Tyler-Smith
authors.affiliation: Centre for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive, MSC 5635, Bethesda, Maryland 20891-5635, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Rotimi
authors.affiliation: Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
authors.affiliation: 1] Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK [2] Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK.
authors.forename: Manjinder S
authors.initials: MS
authors.lastname: Sandhu
mesh_terms: D000349:Africa; D017954:Africa South of the Sahara; D001208:Asia / Q000208:ethnology; D005060:Europe / Q000208:ethnology; D014644:Genetic Variation / Q000235:genetics*; D005826:Genetics, Medical / Q000639:trends*; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics / Q000639:trends*; D006801:Humans; D012307:Risk Factors; D012641:Selection, Genetic / Q000235:genetics