期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-019-13480-z
关键词
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资金
- Wellcome [WT077383/Z/05/Z, 090770/Z/09/Z, 204911/Z/16/Z, 203141/Z/16/Z, 206194]
- Bill & Melinda Gates Foundation through the Foundations of the National Institutes of Health as part of the Grand Challenges in Global Health Initiative [566]
- Medical Research Council [G0600718, G0600230, MR/M006212/1]
- Wellcome Trust [097364/Z/11/Z, 106289/Z/14/Z, 076934/Z/05/Z, 091758/Z/10/Z, 084538, 100956/Z/13/Z]
- European Community [LSHPCT-2004-503578]
- European Community under Seventh Framework Programme (FP7/2007-2013) [242095]
- Oxford University Clinical Academic School Transitional Fellowship
- European Community's Seventh Framework Programme (FP7/2007-2013) [242095-EVIMalaR]
- Central African Network for Tuberculosis, HIV/AIDS and Malaria (CANTAM) - European and Developing Countries Clinical Trials Partnership (EDCTP)
- MRC [G9901439]
- Istituto Pasteur-Fondazione Cenci Bolognetti, BioMalPar and Evimalar (European Community FP6,FP7)
- MRC [G0600230, MR/M006212/1, G0600718] Funding Source: UKRI
- Wellcome Trust [091758/Z/10/Z, 090770/Z/09/Z, 097364/Z/11/Z, 106289/Z/14/Z, 204911/Z/16/Z] Funding Source: Wellcome Trust
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 cases and population controls from 11 countries, informed by sequencing of family trios and by direct typing of candidate loci in an additional 15,000 samples. We identify five replicable associations 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 association in ATP2B4, but are unable to identify a likely causal mechanism at the chromosome 6 locus. Previously reported HLA associations do not replicate in these samples. This large dataset will provide a foundation for further research on thegenetic determinants of malaria resistance in diverse populations.
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