New insights into malaria susceptibility from the genomes of 17,000 individuals from Africa, Asia, and Oceania

Band, G.; Le, Q. S.; Clarke, G. M.; Kivinen, K.; Hubbart, C.; Jeffreys, A. E.; Rowlands, K.; Leffler, E. M.; Jallow, M.; Conway, D. J.; Sisay-Joof, F.; d'Alessandro, U.; Toure, O. B.; Thera, M. A.; Konate, S.; Sissoko, S.; Mangano, V. D.; Bougouma, E. C.; Sirima, S. B.; Amenga-Etego, L. N.; Ghansah, A. K.; Hodgson, A. V. O.; Wilson, M. D.; Enimil, A.; Ansong, D.; Evans, J.; Ademola, S. A.; Apinjoh, T. O.; Ndila, C. M.; Manjurano, A.; Drakeley, C.; Reyburn, H.; Nguyen, H. P.; Nguyen, T. N. Q.; Thai, C. Q.; Hien, T. T.; Teo, Y. Y.; Manning, L.; Laman, M.; Michon, P.; Karunajeewa, H.; Siba, P.

doi:10.1101/535898

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bioRxiv · 10.1101/535898

New insights into malaria susceptibility from the genomes of 17,000 individuals from Africa, Asia, and Oceania

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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.

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Band, G., Le, Q. S., Clarke, G. M., Kivinen, K., Hubbart, C., Jeffreys, A. E., Rowlands, K., Leffler, E. M., Jallow, M., Conway, D. J., Sisay-Joof, F., d'Alessandro, U., Toure, O. B., Thera, M. A., Konate, S., Sissoko, S., Mangano, V. D., Bougouma, E. C., Sirima, S. B., Amenga-Etego, L. N., Ghansah, A. K., Hodgson, A. V. O., Wilson, M. D., Enimil, A., Ansong, D., Evans, J., Ademola, S. A., Apinjoh, T. O., Ndila, C. M., Manjurano, A., Drakeley, C., Reyburn, H., Nguyen, H. P., Nguyen, T. N. Q., Thai, C. Q., Hien, T. T., Teo, Y. Y., Manning, L., Laman, M., Michon, P., Karunajeewa, H., Siba, P.. 2019-02-04. New insights into malaria susceptibility from the genomes of 17,000 individuals from Africa, Asia, and Oceania. https://doi.org/10.1101/535898

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