Publication:
Genome-wide and fine-resolution association analysis of malaria in West Africa

Issued Date

2009-06-01

Resource Type

Article

ISSN

15461718
10614036

DOI

10.1038/ng.388

Other identifier(s)

2-s2.0-67349278465

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Nature Genetics. Vol.41, No.6 (2009), 657-665

Suggested Citation

Muminatou Jallow, Yik Ying Teo, Kerrin S. Small, Kirk A. Rockett, Panos Deloukas, Taane G. Clark, Katja Kivinen, Kalifa A. Bojang, David J. Conway, Margaret Pinder, Giorgio Sirugo, Fatou Sisay-Joof, Stanley Usen, Sarah Auburn, Suzannah J. Bumpstead, Susana Campino, Alison Coffey, Andrew Dunham, Andrew E. Fry, Angela Green, Rhian Gwilliam, Sarah E. Hunt, Michael Inouye, Anna E. Jeffreys, Alieu Mendy, Aarno Palotie, Simon Potter, Jiannis Ragoussis, Jane Rogers, Kate Rowlands, Elilan Somaskantharajah, Pamela Whittaker, Claire Widden, Peter Donnelly, Bryan Howie, Jonathan Marchini, Andrew Morris, Miguel Sanjoaquin, Eric Akum Achidi, Tsiri Agbenyega, Angela Allen, Olukemi Amodu, Patrick Corran, Abdoulaye Djimde, Amagana Dolo, Ogobara K. Doumbo, Chris Drakeley, Sarah Dunstan, Jennifer Evans, Jeremy Farrar, Deepika Fernando, Tran Tinh Hien, Rolf D. Horstmann, Muntaser Ibrahim, Nadira Karunaweera, Gilbert Kokwaro, Kwadwo A. Koram, Martha Lemnge, Julie Makani, Kevin Marsh, Pascal Michon, David Modiano, Malcolm E. Molyneux, Ivo Mueller, Michael Parker, Norbert Peshu, Christopher V. Plowe, Odile Puijalon, John Reeder, Hugh Reyburn, Eleanor M. Riley, Anavaj Sakuntabhai, Pratap Singhasivanon, Sodiomon Sirima, Adama Tall, Terrie E. Taylor, Mahamadou Thera, Marita Troye-Blomberg, Thomas N. Williams, Michael Wilson, Dominic P. Kwiatkowski Genome-wide and fine-resolution association analysis of malaria in West Africa. Nature Genetics. Vol.41, No.6 (2009), 657-665. doi:10.1038/ng.388 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/27218

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Title

Genome-wide and fine-resolution association analysis of malaria in West Africa

Author(s)

Muminatou Jallow
 Yik Ying Teo
 Kerrin S. Small
 Kirk A. Rockett
 Panos Deloukas
 Taane G. Clark
 Katja Kivinen
 Kalifa A. Bojang
 David J. Conway
 Margaret Pinder
 Giorgio Sirugo
 Fatou Sisay-Joof
 Stanley Usen
 Sarah Auburn
 Suzannah J. Bumpstead
 Susana Campino
 Alison Coffey
 Andrew Dunham
 Andrew E. Fry
 Angela Green
 Rhian Gwilliam
 Sarah E. Hunt
 Michael Inouye
 Anna E. Jeffreys
 Alieu Mendy
 Aarno Palotie
 Simon Potter
 Jiannis Ragoussis
 Jane Rogers
 Kate Rowlands
 Elilan Somaskantharajah
 Pamela Whittaker
 Claire Widden
 Peter Donnelly
 Bryan Howie
 Jonathan Marchini
 Andrew Morris
 Miguel Sanjoaquin
 Eric Akum Achidi
 Tsiri Agbenyega
 Angela Allen
 Olukemi Amodu
 Patrick Corran
 Abdoulaye Djimde
 Amagana Dolo
 Ogobara K. Doumbo
 Chris Drakeley
 Sarah Dunstan
 Jennifer Evans
 Jeremy Farrar
 Deepika Fernando
 Tran Tinh Hien
 Rolf D. Horstmann
 Muntaser Ibrahim
 Nadira Karunaweera
 Gilbert Kokwaro
 Kwadwo A. Koram
 Martha Lemnge
 Julie Makani
 Kevin Marsh
 Pascal Michon
 David Modiano
 Malcolm E. Molyneux
 Ivo Mueller
 Michael Parker
 Norbert Peshu
 Christopher V. Plowe
 Odile Puijalon
 John Reeder
 Hugh Reyburn
 Eleanor M. Riley
 Anavaj Sakuntabhai
 Pratap Singhasivanon
 Sodiomon Sirima
 Adama Tall
 Terrie E. Taylor
 Mahamadou Thera
 Marita Troye-Blomberg
 Thomas N. Williams
 Michael Wilson
 Dominic P. Kwiatkowski

Other Contributor(s)

Medical Research Council Laboratories Gambia
 Wellcome Trust Centre for Human Genetics
 Wellcome Trust Sanger Institute
 University of Oxford
 University of Malawi College of Medicine
 University of Buea
 Kwame Nkrumah University of Science and Technology
 Papua New Guinea Institute of Medical Research
 Weatherall Institute of Molecular Medicine
 University of Ibadan
 National Institute for Biological Standards and Control
 University of Bamako
 London School of Hygiene & Tropical Medicine
 Kilimanjaro Christian Medical Centre
 UCL
 Bernhard Nocht Institut fur Tropenmedizin Hamburg
 University of Colombo Faculty of Medicine
 Khartoum University
 Wellcome Trust Research Laboratories Nairobi
 University of Ghana
 National Institute for Medical Research Tanga
 Muhimbili University of Health and Allied Sciences
 Universita degli Studi di Roma La Sapienza
 Blantyre Malaria Project
 University of Maryland, Baltimore
 Institut Pasteur, Paris
 Mahidol University
 Centre National de Recherche et de Formation sur le Paludisme
 Lnstitut Pasteur de Dakar
 Michigan State University
 Department of Molecular Biosciences, The Wenner-Gren Institute

Abstract

We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 × 10 7 to P = 4 × 10 14, with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.

Keyword(s)

Biochemistry, Genetics and Molecular Biology

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/27218

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Scopus 2006-2010