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

Jallow, M., Teo, Y. Y., Small, K. S., Rockett, K. A., Deloukas, P., Clark, T. G., Kivinen, K., Bojang, K. A., Conway, D. J., Pinder, M., et al, Wellcome Trust Case Control Consortium, Brown, Matthew A. and Bradbury, Linda (2009) Genome-wide and fine-resolution association analysis of malaria in West Africa. Nature Genetics, 41 6: 657-665. doi:10.1038/ng.388


Author Jallow, M.
Teo, Y. Y.
Small, K. S.
Rockett, K. A.
Deloukas, P.
Clark, T. G.
Kivinen, K.
Bojang, K. A.
Conway, D. J.
Pinder, M.
et al
Wellcome Trust Case Control Consortium
Brown, Matthew A.
Bradbury, Linda
Title Genome-wide and fine-resolution association analysis of malaria in West Africa
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
Publication date 2009-06
Year available 2009
Sub-type Article (original research)
DOI 10.1038/ng.388
Volume 41
Issue 6
Start page 657
End page 665
Total pages 9
Place of publication United States
Publisher Nature Publishing Gourp
Collection year 2010
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
970111 Expanding Knowledge in the Medical and Health Sciences
920109 Infectious Diseases
060408 Genomics
060405 Gene Expression (incl. Microarray and other genome-wide approaches)
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 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.
Keyword PLASMODIUM-FALCIPARUM MALARIA
BETA-GLOBIN GENE
LINKAGE DISEQUILIBRIUM
NATURAL-SELECTION
HAPLOTYPE MAP
GENOTYPE DATA
HEMOGLOBIN-C
CHILDREN
POPULATION
POWER
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
UQ Diamantina Institute Publications
 
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Created: Wed, 14 Apr 2010, 12:29:06 EST by Kylie Hengst on behalf of UQ Diamantina Institute