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

Gavin Band; Quang Si Le; Geraldine M. Clarke; Katja Kivinen; Christina Hubbart; Anna E. Jeffreys; Kate Rowlands; Ellen M. Leffler; Muminatou Jallow; David J. Conway; Fatoumatta Sisay-Joof; Giorgio Sirugo; Umberto d’Alessandro; Ousmane B. Toure; Mahamadou A. Thera; Salimata Konate; Sibiri Sissoko; Valentina D. Mangano; Edith C. Bougouma; Sodiomon B. Sirima; Lucas N. Amenga-Etego; Anita K. Ghansah; Abraham V. O. Hodgson; Michael D. Wilson; Anthony Enimil; Daniel Ansong; Jennifer Evans; Subulade A. Ademola; Tobias O. Apinjoh; Carolyne M. Ndila; Alphaxard Manjurano; Chris Drakeley; Hugh Reyburn; Nguyen Hoan Phu; Nguyen Thi Ngoc Quyen; Cao Quang Thai; Tran Tinh Hien; Yik Ying Teo; Laurens Manning; Moses Laman; Pascal Michon; Harin Karunajeewa; Peter Siba; Stephen Allen; Angela Allen; Melanie Bahlo; Timothy M. E. Davis; Victoria Cornelius; Jennifer Shelton; Chris C.A. Spencer; George B.J. Busby; Angeliki Kerasidou; Eleanor Drury; Jim Stalker; Alexander Dilthey; Alexander J. Mentzer; Gil McVean; Kalifa A. Bojang; Ogobara Doumbo; David Modiano; Kwadwo A. Koram; Tsiri Agbenyega; Olukemi K. Amodu; Eric Achidi; Thomas N. Williams; Kevin Marsh; Eleanor M. Riley; Malcolm Molyneux; Terrie Taylor; Sarah J. Dunstan; Jeremy Farrar; Ivo Mueller; Kirk A. Rockett; Dominic P. Kwiatkowski

doi:10.1038/s41467-019-13480-z

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

Gavin Band
, Quang Si Le
, Geraldine M. Clarke
, Katja Kivinen
, Christina Hubbart
, Anna E. Jeffreys
, Kate Rowlands
, Ellen M. Leffler
, Muminatou Jallow
, David J. Conway
, Fatoumatta Sisay-Joof
, Giorgio Sirugo
, Umberto d’Alessandro
, Ousmane B. Toure
, Mahamadou A. Thera
, Salimata Konate
, Sibiri Sissoko
, Valentina D. Mangano
, Edith C. Bougouma
, Sodiomon B. Sirima

Lucas N. Amenga-Etego, Anita K. Ghansah, Abraham V. O. Hodgson, Michael D. Wilson, Anthony Enimil, Daniel Ansong, Jennifer Evans, Subulade A. Ademola, Tobias O. Apinjoh, Carolyne M. Ndila, Alphaxard Manjurano, Chris Drakeley, Hugh Reyburn, Nguyen Hoan Phu, Nguyen Thi Ngoc Quyen, Cao Quang Thai, Tran Tinh Hien, Yik Ying Teo, Laurens Manning, Moses Laman, Pascal Michon, Harin Karunajeewa, Peter Siba, Stephen Allen, Angela Allen, Melanie Bahlo, Timothy M. E. Davis, Victoria Cornelius, Jennifer Shelton, Chris C.A. Spencer, George B.J. Busby, Angeliki Kerasidou, Eleanor Drury, Jim Stalker, Alexander Dilthey, Alexander J. Mentzer, Gil McVean, Kalifa A. Bojang, Ogobara Doumbo, David Modiano, Kwadwo A. Koram, Tsiri Agbenyega, Olukemi K. Amodu, Eric Achidi, Thomas N. Williams, Kevin Marsh, Eleanor M. Riley, Malcolm Molyneux, Terrie Taylor, Sarah J. Dunstan, Jeremy Farrar, Ivo Mueller, Kirk A. Rockett, Dominic P. Kwiatkowski

Clinical Sciences

Research output: Contribution to journal › Article › peer-review

109 Citations (Scopus)

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.

Original language	English
Article number	5732
Journal	Nature Communications
Volume	10
Issue number	1
Early online date	16 Dec 2019
DOIs	https://doi.org/10.1038/s41467-019-13480-z
Publication status	E-pub ahead of print - 16 Dec 2019

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-019-13480-zLicence: CC BY

2019-07-02 MalariaGEN GWAS Supplementary1Other version, 28.4 MBLicence: CC BY
Figure 01 - data and structureOther version, 877 KBLicence: CC BY
Figure 02 - manhattanOther version, 267 KBLicence: CC BY
Figure 03 - rs6241876Other version, 449 KBLicence: CC BY
Figure 04 - patterns of risk v6Other version, 9.7 KBLicence: CC BY
Figure 05 - ATP2B4Other version, 2.17 MBLicence: CC BY
Figure 06 - HLAOther version, 2.76 MBLicence: CC BY
Supplementary tablesOther version, 838 KBLicence: CC BY
535898v2Accepted author manuscript, 25.2 MBLicence: CC BY

Cite this

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., Sirugo, G., d’Alessandro, U., Toure, O. B., Thera, M. A., Konate, S., Sissoko, S., Mangano, V. D., Bougouma, E. C., ... Kwiatkowski, D. P. (2019). Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania. Nature Communications, 10(1), Article 5732. Advance online publication. https://doi.org/10.1038/s41467-019-13480-z

@article{f0cb95e87692451eb8592255ba614180,

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

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 \textasciitilde{} 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.",

author = "Gavin Band and Le, \{Quang Si\} and Clarke, \{Geraldine M.\} and Katja Kivinen and Christina Hubbart and Jeffreys, \{Anna E.\} and Kate Rowlands and Leffler, \{Ellen M.\} and Muminatou Jallow and Conway, \{David J.\} and Fatoumatta Sisay-Joof and Giorgio Sirugo and Umberto d{\textquoteright}Alessandro and Toure, \{Ousmane B.\} and Thera, \{Mahamadou A.\} and Salimata Konate and Sibiri Sissoko and Mangano, \{Valentina D.\} and Bougouma, \{Edith C.\} and Sirima, \{Sodiomon B.\} and Amenga-Etego, \{Lucas N.\} and Ghansah, \{Anita K.\} and Hodgson, \{Abraham V. O.\} and Wilson, \{Michael D.\} and Anthony Enimil and Daniel Ansong and Jennifer Evans and Ademola, \{Subulade A.\} and Apinjoh, \{Tobias O.\} and Ndila, \{Carolyne M.\} and Alphaxard Manjurano and Chris Drakeley and Hugh Reyburn and Phu, \{Nguyen Hoan\} and \{Ngoc Quyen\}, \{Nguyen Thi\} and Thai, \{Cao Quang\} and Hien, \{Tran Tinh\} and Teo, \{Yik Ying\} and Laurens Manning and Moses Laman and Pascal Michon and Harin Karunajeewa and Peter Siba and Stephen Allen and Angela Allen and Melanie Bahlo and Davis, \{Timothy M. E.\} and Victoria Cornelius and Jennifer Shelton and Spencer, \{Chris C.A.\} and Busby, \{George B.J.\} and Angeliki Kerasidou and Eleanor Drury and Jim Stalker and Alexander Dilthey and Mentzer, \{Alexander J.\} and Gil McVean and Bojang, \{Kalifa A.\} and Ogobara Doumbo and David Modiano and Koram, \{Kwadwo A.\} and Tsiri Agbenyega and Amodu, \{Olukemi K.\} and Eric Achidi and Williams, \{Thomas N.\} and Kevin Marsh and Riley, \{Eleanor M.\} and Malcolm Molyneux and Terrie Taylor and Dunstan, \{Sarah J.\} and Jeremy Farrar and Ivo Mueller and Rockett, \{Kirk A.\} and Kwiatkowski, \{Dominic P.\}",

year = "2019",

month = dec,

day = "16",

doi = "10.1038/s41467-019-13480-z",

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Band, G, Le, QS, Clarke, GM, Kivinen, K, Hubbart, C, Jeffreys, AE, Rowlands, K, Leffler, EM, Jallow, M, Conway, DJ, Sisay-Joof, F, Sirugo, G, d’Alessandro, U, Toure, OB, Thera, MA, Konate, S, Sissoko, S, Mangano, VD, Bougouma, EC, Sirima, SB, Amenga-Etego, LN, Ghansah, AK, Hodgson, AVO, Wilson, MD, Enimil, A, Ansong, D, Evans, J, Ademola, SA, Apinjoh, TO, Ndila, CM, Manjurano, A, Drakeley, C, Reyburn, H, Phu, NH, Ngoc Quyen, NT, Thai, CQ, Hien, TT, Teo, YY, Manning, L, Laman, M, Michon, P, Karunajeewa, H, Siba, P, Allen, S, Allen, A, Bahlo, M, Davis, TME, Cornelius, V, Shelton, J, Spencer, CCA, Busby, GBJ, Kerasidou, A, Drury, E, Stalker, J, Dilthey, A, Mentzer, AJ, McVean, G, Bojang, KA, Doumbo, O, Modiano, D, Koram, KA, Agbenyega, T, Amodu, OK, Achidi, E, Williams, TN, Marsh, K, Riley, EM, Molyneux, M, Taylor, T, Dunstan, SJ, Farrar, J, Mueller, I, Rockett, KA & Kwiatkowski, DP 2019, 'Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania', Nature Communications, vol. 10, no. 1, 5732. https://doi.org/10.1038/s41467-019-13480-z

TY - JOUR

T1 - Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania

AU - Band, Gavin

AU - Le, Quang Si

AU - Clarke, Geraldine M.

AU - Kivinen, Katja

AU - Hubbart, Christina

AU - Jeffreys, Anna E.

AU - Rowlands, Kate

AU - Leffler, Ellen M.

AU - Jallow, Muminatou

AU - Conway, David J.

AU - Sisay-Joof, Fatoumatta

AU - Sirugo, Giorgio

AU - d’Alessandro, Umberto

AU - Toure, Ousmane B.

AU - Thera, Mahamadou A.

AU - Konate, Salimata

AU - Sissoko, Sibiri

AU - Mangano, Valentina D.

AU - Bougouma, Edith C.

AU - Sirima, Sodiomon B.

AU - Amenga-Etego, Lucas N.

AU - Ghansah, Anita K.

AU - Hodgson, Abraham V. O.

AU - Wilson, Michael D.

AU - Enimil, Anthony

AU - Ansong, Daniel

AU - Evans, Jennifer

AU - Ademola, Subulade A.

AU - Apinjoh, Tobias O.

AU - Ndila, Carolyne M.

AU - Manjurano, Alphaxard

AU - Drakeley, Chris

AU - Reyburn, Hugh

AU - Phu, Nguyen Hoan

AU - Ngoc Quyen, Nguyen Thi

AU - Thai, Cao Quang

AU - Hien, Tran Tinh

AU - Teo, Yik Ying

AU - Manning, Laurens

AU - Laman, Moses

AU - Michon, Pascal

AU - Karunajeewa, Harin

AU - Siba, Peter

AU - Allen, Stephen

AU - Allen, Angela

AU - Bahlo, Melanie

AU - Davis, Timothy M. E.

AU - Cornelius, Victoria

AU - Shelton, Jennifer

AU - Spencer, Chris C.A.

AU - Busby, George B.J.

AU - Kerasidou, Angeliki

AU - Drury, Eleanor

AU - Stalker, Jim

AU - Dilthey, Alexander

AU - Mentzer, Alexander J.

AU - McVean, Gil

AU - Bojang, Kalifa A.

AU - Doumbo, Ogobara

AU - Modiano, David

AU - Koram, Kwadwo A.

AU - Agbenyega, Tsiri

AU - Amodu, Olukemi K.

AU - Achidi, Eric

AU - Williams, Thomas N.

AU - Marsh, Kevin

AU - Riley, Eleanor M.

AU - Molyneux, Malcolm

AU - Taylor, Terrie

AU - Dunstan, Sarah J.

AU - Farrar, Jeremy

AU - Mueller, Ivo

AU - Rockett, Kirk A.

AU - Kwiatkowski, Dominic P.

PY - 2019/12/16

Y1 - 2019/12/16

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-019-13480-z

DO - 10.1038/s41467-019-13480-z

M3 - Article

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5732

ER -

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

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this