Journal article
Insights into malaria susceptibility using genome - wide data on 17,000 individuals from Africa, Asia and Oceania
- Abstract:
- 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 the genetic determinants of malaria resistance in diverse populations.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 5.1MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-019-13480-z
Authors
+ Wellcome Trust
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- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 077383/Z/05/ZZ
+ Medical Research Council
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- Funder identifier:
- https://ror.org/03x94j517
- Grant:
- G0600718
- Publisher:
- Nature Research
- Journal:
- Nature Communications More from this journal
- Volume:
- 10
- Article number:
- 5732
- Publication date:
- 2019-12-16
- Acceptance date:
- 2019-11-11
- DOI:
- EISSN:
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2041-1723
- ISSN:
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2041-1723
- Language:
-
English
- Keywords:
- Pubs id:
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pubs:1071344
- UUID:
-
uuid:4f6fa1d6-210c-48f0-8955-b103dbfa4382
- Local pid:
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pubs:1071344
- Source identifiers:
-
1071344
- Deposit date:
-
2019-11-12
- ARK identifier:
Terms of use
- Copyright holder:
- Band et al.
- Copyright date:
- 2019
- Rights statement:
- Copyright © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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