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

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; Wellcome Trust Case Control Consor

doi:10.1038/ng.388

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

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

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, …

Nature genetics, Vol.41(6), pp.657-665

01/06/2009

DOI: https://doi.org/10.1038/ng.388

PMCID: PMC2889040

PMID: 19465909

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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 x 10(-7) to P = 4 x 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.

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Title: Genome-wide and fine-resolution association analysis of malaria in West Africa
Creators - without role: Muminatou Jallow - Massachusetts Rehabilitation Commission
Yik Ying Teo - University of Oxford
Kerrin S. Small - University of Oxford
Kirk A. Rockett - University of Oxford
Panos Deloukas - Wellcome Sanger Institute
Taane G. Clark - University of Oxford
Katja Kivinen - Wellcome Sanger Institute
Kalifa A. Bojang - Massachusetts Rehabilitation Commission
David J. Conway - Massachusetts Rehabilitation Commission
Margaret Pinder - Massachusetts Rehabilitation Commission
Giorgio Sirugo - Massachusetts Rehabilitation Commission
Fatou Sisay-Joof - Massachusetts Rehabilitation Commission
Stanley Usen - Massachusetts Rehabilitation Commission
Sarah Auburn - University of Oxford
Suzannah J. Bumpstead - Wellcome Sanger Institute
Susana Campino - University of Oxford
Alison Coffey - Wellcome Sanger Institute
Andrew Dunham - Wellcome Sanger Institute
Andrew E. Fry - University of Oxford
Angela Green - University of Oxford
Rhian Gwilliam - Wellcome Sanger Institute
Sarah E. Hunt - Wellcome Sanger Institute
Michael Inouye - Wellcome Sanger Institute
Anna E. Jeffreys - University of Oxford
Alieu Mendy - University of Oxford
Aarno Palotie - Wellcome Sanger Institute
Simon Potter - Wellcome Sanger Institute
Jiannis Ragoussis - University of Oxford
Jane Rogers - University of Oxford
Kate Rowlands - University of Oxford
Elilan Somaskantharajah - Wellcome Sanger Institute
Pamela Whittaker - Wellcome Sanger Institute
Claire Widden - Wellcome Sanger Institute
Peter Donnelly - University of Oxford
Bryan Howie - University of Oxford
Jonathan Marchini - University of Oxford
Andrew Morris - University of Oxford
Miguel SanJoaquin - Wellcome Sanger Institute
Eric Akum Achidi - University of Buea
Tsiri Agbenyega - Kwame Nkrumah University
Angela Allen - College Station Medical Center
Olukemi Amodu - University of Ibadan
Patrick Corran - Natl Inst Biol Stand & Controls, Potters Bar, Herts, England
Abdoulaye Djimde - University of Bamako
Amagana Dolo - University of Bamako
Ogobara K. Doumbo - University of Bamako
Chris Drakeley - Supreme Council Of Health
Sarah Dunstan - University of Oxford
Jennifer Evans - Kwame Nkrumah University
Jeremy Farrar - University of Oxford
Deepika Fernando - University of Colombo
Tran Tinh Hien - University of Oxford
Rolf D. Horstmann - College Station Medical Center
Muntaser Ibrahim - University of Khartoum
Nadira Karunaweera - University of Colombo
Gilbert Kokwaro - Wellcome Trust
Kwadwo A. Koram - University of Ghana
Martha Lemnge - College Station Medical Center
Julie Makani - Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania
Kevin Marsh - Wellcome Trust
Pascal Michon - College Station Medical Center
David Modiano - Univ Roma La Sapienza, Rome, Italy
Malcolm E. Molyneux - University of Malawi
Ivo Mueller - College Station Medical Center
Michael Parker - University of Oxford
Norbert Peshu - Wellcome Trust
Christopher V. Plowe - Blantyre Malaria Project, Blantyre 3, Malawi
Odile Puijalon - Inst Pasteur, Unite Immunol Mol Parasites, Paris, France
John Reeder - College Station Medical Center
Hugh Reyburn - Supreme Council Of Health
Eleanor M. Riley - Supreme Council Of Health
Anavaj Sakuntabhai - Inst Pasteur, Unite Immunol Mol Parasites, Paris, France
Pratap Singhasivanon - Mahidol University
Sodiomon Sirima - Ctr Natl Rech & Format Paludisme, Ouagadougou, Burkina Faso
Adama Tall - Inst Pasteur, Dakar, Senegal
Terrie E. Taylor - Blantyre Malaria Project, Blantyre 3, Malawi
Mahamadou Thera - University of Bamako
Marita Troye-Blomberg - Stockholm University
Thomas N. Williams - Wellcome Trust
Michael Wilson - University of Ghana
Dominic P. Kwiatkowski - University of Oxford
Wellcome Trust Case Control Consor
Publication Details: Nature genetics, Vol.41(6), pp.657-665
Publisher: Springer Nature
Number of pages: 9
Grant note: Bill & Melinda Gates Foundation; CGIAR G0800759; G9828345; G0600230; MC_U190081993; MC_U190081977; G19/9; G0600718; G0600329; G0800675 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) G9828345; MC_U190081993; G0800675; G0800759; G0600718; MC_U190081977; G0600230; G19/9; G0600329 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 566 / Foundation for the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA CZB/4/540 / Chief Scientist Office 077383/Z/05/Z / Wellcome Trust G0600230 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
Identifiers: 9938621108331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article