Fig. 2: Evidence for association with severe malaria.
a Association evidence (log10 BFavg, y axis; clamped to a maximum of 12) at typed and imputed SNPs and indels genome-wide (x axis). BFavg reflects evidence under a range of models summarized using prior weights specified in Methods. Shapes denote whether the model with the highest posterior weight is for effects fixed across populations and subphenotypes (case–control effect, circles), or suggests variation in effect between populations (crosses) or between subphenotypes (plusses). b Comparison of model-averaged Bayes factor (log10 BFavg, y axis) and the evidence under an additive model of association with overall SM (−log10 Padd, x axis). For visualization purposes, we have removed variants in the region of rs334 (HbS, chromosome 11) and rs567544458 (glycophorin region, chromosome 4) except the lead variant. Shapes are as in a. The values for rs334 and rs8176719 lie outside the plot as indicated by arrows; to visualize these we have projected them onto the plot boundary. c Twelve regions of the genome with BFavg > 10,000. Columns reflect the ID, genomic position, reference, and alternative allele with estimated protective allele indicated in bold, log10 BFavg, −log10 P-value for an additive model of association with SM or with SM subtypes, nearest gene and distance to the nearest gene for intergenic variants, known linked phenotypes and combined protective allele frequency across African control and case samples. Bar plots summarize our inference about the mode of effect of the protective allele and the distribution of effects between SM subtypes and between populations. The last column reflects the evidence for association observed in replication samples (log10 BFreplication), assessed using the effect-size distribution learnt from discovery samples, based on direct typing of tag SNPs as detailed in Supplementary Data 1. Rows are in bold if they showed positive replication evidence (BFreplication > 1). d Comparison of estimated effect sizes for the protective allele on CM (y axis) and on unspecified SM cases (x axis) for the 12 variants in c. The 95% confidence region for rs334 and rs62418762 (dashed ellipses) are shown. Source data are provided as a Source Data file.
