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

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Band, Gavin, Le, Quang Si, Clarke, Geraldine M., Kivinen, Katja, Hubbart, Christina, Jeffreys, Anna E., Rowlands, Kate, Leffler, Ellen M., Jallow, Muminatou, Conway, David J., Sisay-Joof, Fatoumatta, Sirugo, Giorgio, d’Alessandro, Umberto, Toure, Ousmane B., Thera, Mahamadou A., Konate, Salimata, Sissoko, Sibiri, Mangano, Valentina D., Bougouma, Edith C., Sirima, Sodiomon B., Amenga-Etego, Lucas N., Ghansah, Anita K., Hodgson, Abraham V. O., Wilson, Michael D., Enimil, Anthony, Ansong, Daniel, Evans, Jennifer, Ademola, Subulade A., Apinjoh, Tobias O., Ndila, Carolyne M., Manjurano, Alphaxard, Drakeley, Chris, Reyburn, Hugh, Phu, Nguyen Hoan, Ngoc Quyen, Nguyen Thi, Thai, Cao Quang, Hien, Tran Tinh, Teo, Yik Ying, Manning, Laurens, Laman, Moses, Michon, Pascal, Karunajeewa, Harin, Siba, Peter, Allen, Steve ORCID: https://orcid.org/0000-0001-6675-249X, Allen, Angela, Bahlo, Melanie, Davis, Timothy M. E., Cornelius, Victoria, Shelton, Jennifer, Spencer, Chris C.A., Busby, George B.J., Kerasidou, Angeliki, Drury, Eleanor, Stalker, Jim, Dilthey, Alexander, Mentzer, Alexander J., McVean, Gil, Bojang, Kalifa A., Doumbo, Ogobara, Modiano, David, Koram, Kwadwo A., Agbenyega, Tsiri, Amodu, Olukemi K., Achidi, Eric, Williams, Thomas N., Marsh, Kevin, Riley, Eleanor M., Molyneux, Malcolm, Taylor, Terrie, Dunstan, Sarah J., Farrar, Jeremy, Mueller, Ivo, Rockett, Kirk A. and Kwiatkowski, Dominic P. (2019) 'Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania'. Nature Communications, Vol 10, Issue 5732.

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Abstract

We conducted a genome-wide association study of host resistance to severe Plasmodium falciparum malaria in over 17,000 individuals from 11 malaria- endemic countries, undertaking a wide ranging analysis which identifies five replicable associations with genome-wide levels of evidence. Our findings include a newly implicated variant on chromosome 6 associated with risk of cerebral malaria, and the discovery of an erythroid-specific transcription start site underlying the association in ATP2B4. Previously reported HLA associations cannot be replicated in this dataset. We estimate substantial heritability of severe malaria (h2 ~ 23%), of which around 10% is explained by the currently identified associations. Our dataset will provide a major building block for future research on the genetic determinants of disease in these diverse human populations.

Item Type: Article
Subjects: QU Biochemistry > Genetics > QU 460 Genomics. Proteomics
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 755 Epidemiology
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1038/s41467-019-13480-z
Depositing User: Marie Hatton
Date Deposited: 06 Jan 2020 16:49
Last Modified: 06 Jan 2020 16:49
URI: https://archive.lstmed.ac.uk/id/eprint/13321

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