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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Imputation-Based Meta-Analysis of Severe Malaria in Three African Populations
PLoS Genetics, Volume 9, No. 5, Article e1003509, Year 2013
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Description
Combining data from genome-wide association studies (GWAS) conducted at different locations, using genotype imputation and fixed-effects meta-analysis, has been a powerful approach for dissecting complex disease genetics in populations of European ancestry. Here we investigate the feasibility of applying the same approach in Africa, where genetic diversity, both within and between populations, is far more extensive. We analyse genome-wide data from approximately 5,000 individuals with severe malaria and 7,000 population controls from three different locations in Africa. Our results show that the standard approach is well powered to detect known malaria susceptibility loci when sample sizes are large, and that modern methods for association analysis can control the potential confounding effects of population structure. We show that pattern of association around the haemoglobin S allele differs substantially across populations due to differences in haplotype structure. Motivated by these observations we consider new approaches to association analysis that might prove valuable for multicentre GWAS in Africa: we relax the assumptions of SNP-based fixed effect analysis; we apply Bayesian approaches to allow for heterogeneity in the effect of an allele on risk across studies; and we introduce a region-based test to allow for heterogeneity in the location of causal alleles. © 2013 Band et al.
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Authors & Co-Authors
Band, Gavin
Unknown Affiliation
Le, Si Quang
Unknown Affiliation
Jostins, Luke
Unknown Affiliation
Pirinen, Matti J.
Unknown Affiliation
Kivinen, Katja J.
Unknown Affiliation
Jallow, Muminatou
Unknown Affiliation
Sisay-Joof, Fatoumatta
Unknown Affiliation
Bojang, Kalifa A.
Unknown Affiliation
Pinder, Margaret
Unknown Affiliation
Sirugo, G.
Unknown Affiliation
Conway, David J.
Unknown Affiliation
Nyirongo, Vysaul
Unknown Affiliation
Kachala, David
Unknown Affiliation
Molyneux, Malcolm Edward
Unknown Affiliation
Taylor, Terrie Ellen
Unknown Affiliation
Ndila, Carolyne M.
Unknown Affiliation
Peshu, Norbert M.
Unknown Affiliation
Marsh, Kevin
Unknown Affiliation
Williams, Thomas Neil
Unknown Affiliation
Alcock, Dan
Unknown Affiliation
Andrews, Robert M.
Unknown Affiliation
Edkins, Sarah J.
Unknown Affiliation
Gray, Emma K.
Unknown Affiliation
Hubbart, Christina S.
Unknown Affiliation
Jeffreys, Anna E.
Unknown Affiliation
Rowlands, Kate
Unknown Affiliation
Schuldt, Kathrin
Unknown Affiliation
Clark, Taane Gregory
Unknown Affiliation
Small, Kerrin S.
Unknown Affiliation
Teo, Yik Ying
Unknown Affiliation
Kwiatkowski, Dominic P.
Unknown Affiliation
Rockett, Kirk A.
Unknown Affiliation
Barrett, Jeffrey Carl
Unknown Affiliation
Spencer, Chris C.A.
Unknown Affiliation
Statistics
Citations: 100
Authors: 34
Affiliations: 12
Identifiers
Doi:
10.1371/journal.pgen.1003509
e-ISSN:
15537404
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study
Study Approach
Systematic review