Nature Communications 2019; 10(1): 5732 -

Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania.

Malaria Genomic Epidemiology Network.
- "The human genetic factors that affect resistance to infectious disease are poorly understood. Here we report a genome-wide association study in 17,000 severe malaria\xC2\xA0cases and population controls from\xC2\xA011 countries, informed by sequencing of family trios and by direct typing of candidate loci\xC2\xA0in an additional\xC2\xA015,000 samples. We identify five replicable\xC2\xA0associations with genome-wide levels of evidence including a newly implicated variant on chromosome 6. Jointly, these variants account for around one-tenth of the heritability of severe malaria, which we estimate as ~23% using genome-wide genotypes. We interrogate available functional data and discover an erythroid-specific transcription start site underlying the known\xC2\xA0association in ATP2B4, but are unable to identify a likely causal mechanism at the chromosome 6 locus. \xC2\xA0Previously reported HLA associations do not replicate in these samples.\xC2\xA0This large dataset will\xC2\xA0provide a foundation for further research on thegenetic determinants of malaria resistance in diverse populations."