Fig. 3: Evidence for association at rs62418762.
a Regional hitplot showing evidence for association (log10 BFavg, y axis) across a 2.5 Mb region surrounding rs62418762 (x axis). Points are coloured by LD with rs62418762, estimated using African reference panel haplotypes. Directly typed SNPs included in the phased dataset are denoted by black plusses. Below, the locations of significant tissue-specific eQTLs, previously identified association signals, regional genes, pseudogenes and noncoding RNAs, and the Hapmap-combined recombination rate map are annotated. b Detail of discovery and replication evidence for association at rs62418762 under an additive model. Points and lines represent the estimated odds ratio of the ‘C’ allele on severe malaria subtypes. Estimates are obtained using multinomial logistic regression in each population and combined across populations using fixed-effect meta-analysis. Top: effect sizes estimated from imputed genotypes in discovery samples. A Wald test P-value against the null that all three effect sizes are zero is shown. Middle: effect sizes estimated from direct typing of rs62418762 in replication samples. P-value reflects the alternative hypothesis that CM and SMA effects are nonzero and in the direction observed in discovery and is computed by simulation. Bottom: meta-analysis of discovery and replication results. c Empirical null distribution of the discovery BFavg, computed using simulations conditional on the observed frequencies of rs62418762. The red line indicates the observed BFavg and an empirical P-value from the simulated distribution is shown. Source data are provided as a Source Data file.
