Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1371/journal.pgen.1003509

Type

Journal article

Journal

PLoS Genet

Publication Date

05/2013

Volume

9

Keywords

Africa, African Continental Ancestry Group, Bayes Theorem, Chromosome Mapping, Genetic Heterogeneity, Genetic Predisposition to Disease, Genetic Variation, Genetics, Population, Genome, Human, Genome-Wide Association Study, Haplotypes, Hemoglobin, Sickle, Humans, Linkage Disequilibrium, Malaria, Polymorphism, Single Nucleotide