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

M Jallow; YY Teo; KS Small; KA Rockett; P Deloukas; TG Clark; K Kivinen; KA Bojang; DJ Conway; M Pinder; G Sirugo; F Sisay-Joof; S Usen; S Auburn; SJ Bumpstead; S Campino; A Coffey; A Dunham; AE Fry; A Green; R Gwilliam; SE Hunt; M Inouye; AE Jeffreys; A Mendy; A Palotie; S Potter; J Ragoussis; J Rogers; K Rowlands; E Somaskantharajah; P Whittaker; C Widden; P Donnelly; B Howie; J Marchini; A Morris; M Sanjoaquin; EA Achidi; T Agbenyega; A Allen; O Amodu; P Corran; A Djimde; A Dolo; OK Doumbo; C Drakeley; S Dunstan; J Evans; J Farrar; D Fernando; TT Hien; RD Horstmann; M Ibrahim; N Karunaweera; G Kokwaro; KA Koram; M Lemnge; J Makani; K Marsh; P Michon; D Modiano; ME Molyneux; I Mueller; M Parker; N Peshu; CV Plowe; O Puijalon; J Reeder; H Reyburn; EM Riley; A Sakuntabhai; P Singhasivanon; S Sirima; A Tall; TE Taylor; M Thera; M Troye-Blomberg; TN Williams; M Wilson; DP Kwiatkowski

Journal article

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

M Jallow, YY Teo, KS Small, KA Rockett, P Deloukas, TG Clark, K Kivinen, KA Bojang, DJ Conway, M Pinder, G Sirugo, F Sisay-Joof, S Usen, S Auburn, SJ Bumpstead, S Campino, A Coffey, A Dunham, AE Fry, A Green Show all

Nature Genetics | NATURE PUBLISHING GROUP | Published : 2009

DOI: 10.1038/ng.388

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...

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University of Melbourne Researchers

Sarah Dunstan Author

Ivo Mueller Author

Grants

Awarded by Bill and Melinda Gates Foundation

Funding Acknowledgements

We thank the Gambian children and their parents and guardians who made this study possible; and the doctors, nurses and fieldworkers at the Royal Victoria Hospital, Banjul and other health clinics who assisted with this work. MalariaGEN's primary funding is from the Wellcome Trust (grant number 077383/Z/05/Z) and from the Bill & Melinda Gates Foundation, through the Foundation for the National Institutes of Health (grant number 566) as part of the Grand Challenges in Global Health initiative. The Wellcome Trust (Sanger Institute core funding) and the Medical Research Council (grant number G0600230) provide additional support for genotyping, bioinformatics and analysis. The MalariaGEN Resource Centre is part of the European Union Network of Excellence on the Biology and Pathology of Malaria Parasites.