New Results
New insights into malaria susceptibility from the genomes of 17,000 individuals from Africa, Asia, and Oceania
Malaria Genomic Epidemiology Network, View ORCID ProfileGavin 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, Steve 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, View ORCID ProfileGil McVean, Kalifa A. Bojang, Ogobara Doumbo, David Modiano, Kwadwo A. Koram, Tsiri Agbenyega, Olukemi K. Amodu, Eric Achidi, Thomas N. Williams, Kevin Marsh, View ORCID ProfileEleanor M. Riley, Malcolm Molyneux, Terrie Taylor, View ORCID ProfileSarah J. Dunstan, Jeremy Farrar, Ivo Mueller, Kirk A. Rockett, Dominic P. Kwiatkowski
doi: https://doi.org/10.1101/535898
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Gavin Band
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
2Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
3Big Data Institute, Li Ka Shing Centre for Health and Information Discovery, Old Road Campus, Oxford OX3 7LF
Quang Si Le
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Geraldine M. Clarke
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Katja Kivinen
2Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
Christina Hubbart
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Anna E. Jeffreys
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Kate Rowlands
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Ellen M. Leffler
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
2Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
Muminatou Jallow
4Medical Research Council Unit, Atlantic Boulevard, Serrekunda, The Gambia
5Royal Victoria Teaching Hospital, Independence Drive, Banjul, The Gambia
David J. Conway
4Medical Research Council Unit, Atlantic Boulevard, Serrekunda, The Gambia
6Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK
Fatoumatta Sisay-Joof
4Medical Research Council Unit, Atlantic Boulevard, Serrekunda, The Gambia
Giorgio Sirugo
4Medical Research Council Unit, Atlantic Boulevard, Serrekunda, The Gambia
Umberto d’Alessandro
4Medical Research Council Unit, Atlantic Boulevard, Serrekunda, The Gambia
Ousmane B. Toure
7Malaria Research and Training Centre, Faculty of Medicine, University of Bamako, Bamako, Mali
Mahamadou A. Thera
7Malaria Research and Training Centre, Faculty of Medicine, University of Bamako, Bamako, Mali
Salimata Konate
7Malaria Research and Training Centre, Faculty of Medicine, University of Bamako, Bamako, Mali
Sibiri Sissoko
7Malaria Research and Training Centre, Faculty of Medicine, University of Bamako, Bamako, Mali
Valentina D. Mangano
8University of Rome La Sapienza, Italy
Edith C. Bougouma
9Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou, Burkina Faso
Sodiomon B. Sirima
9Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou, Burkina Faso
Lucas N. Amenga-Etego
10Navrongo Health Research Centre, Navrongo, Ghana
Anita K. Ghansah
11Noguchi Memorial Institute for Medical Research, Accra, Ghana
Abraham V. O. Hodgson
10Navrongo Health Research Centre, Navrongo, Ghana
Michael D. Wilson
11Noguchi Memorial Institute for Medical Research, Accra, Ghana
Anthony Enimil
12Komfo Anokye Teaching Hospital, Kumasi, Ghana
Daniel Ansong
12Komfo Anokye Teaching Hospital, Kumasi, Ghana
13Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Jennifer Evans
14Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Postfach 30 41 2, D-20324 Hamburg, Germany
15Kumasi Centre for Collaborative Research, Kumasi, Ghana
Subulade A. Ademola
16Institute of Child Health, College of Medicine, University of Ibadan, Nigeria
Tobias O. Apinjoh
17Department of Biochemistry & Molecular Biology, University of Buea, Buea, South West Region, Cameroon
Carolyne M. Ndila
18KEMRI-Wellcome Trust Research Programme, PO Box 230, Kilifi, Kenya
Alphaxard Manjurano
19Joint Malaria Programme, Kilimanjaro Christian Medical Centre, PO box 2228, Moshi, Tanzania
6Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK
20National Institute for Medical Research, Mwanza Research Centre, Tanzania
Chris Drakeley
19Joint Malaria Programme, Kilimanjaro Christian Medical Centre, PO box 2228, Moshi, Tanzania
6Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK
Hugh Reyburn
19Joint Malaria Programme, Kilimanjaro Christian Medical Centre, PO box 2228, Moshi, Tanzania
6Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK
Nguyen Hoan Phu
21Oxford University Clinical Research Unit, 764 Vo Van Kiet, District 5, Ho Chi Minh City, VietNam
22Hospital for Tropical Diseases, 764 Vo Van Kiet, District 5, Ho Chi Minh City, VietNam
Nguyen Thi Ngoc Quyen
21Oxford University Clinical Research Unit, 764 Vo Van Kiet, District 5, Ho Chi Minh City, VietNam
Cao Quang Thai
21Oxford University Clinical Research Unit, 764 Vo Van Kiet, District 5, Ho Chi Minh City, VietNam
22Hospital for Tropical Diseases, 764 Vo Van Kiet, District 5, Ho Chi Minh City, VietNam
Tran Tinh Hien
21Oxford University Clinical Research Unit, 764 Vo Van Kiet, District 5, Ho Chi Minh City, VietNam
22Hospital for Tropical Diseases, 764 Vo Van Kiet, District 5, Ho Chi Minh City, VietNam
Yik Ying Teo
23Saw Swee Hock School of Public Health, Tahir Foundation Building, National University of Singapore, 12 Science Drive 2, #10-01, Singapore 117549
Laurens Manning
24Papua New Guinea Institute of Medical Research, PO Box 60, Garoka, EHP441, PNG
25University of Western Australia, Perth, Australia
Moses Laman
24Papua New Guinea Institute of Medical Research, PO Box 60, Garoka, EHP441, PNG
Pascal Michon
26Faculty of Medicine and Health Sciences, Divine Word University, Madang, Papua New Guinea
Harin Karunajeewa
27The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Peter Siba
24Papua New Guinea Institute of Medical Research, PO Box 60, Garoka, EHP441, PNG
Steve Allen
28Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA UK
Angela Allen
29Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK
Melanie Bahlo
27The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Timothy M. E. Davis
25University of Western Australia, Perth, Australia
Victoria Cornelius
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
3Big Data Institute, Li Ka Shing Centre for Health and Information Discovery, Old Road Campus, Oxford OX3 7LF
Jennifer Shelton
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Chris C.A. Spencer
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
George B.J. Busby
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
3Big Data Institute, Li Ka Shing Centre for Health and Information Discovery, Old Road Campus, Oxford OX3 7LF
Angeliki Kerasidou
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
30The Ethox Centre, Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF
31Wellcome Centre for Ethics and Humanities, Nuffield Department of Population Health, Big Data Institute, Li Ka Shing Centre for Health and Information Discovery, Old Road Campus, Oxford OX3 7LF
Eleanor Drury
2Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
Jim Stalker
2Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
Alexander Dilthey
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
32Institute of Medical Microbiology, University Hospital of Dusseldorf, Dusseldorf, North Rhine-Westphalia, Germany
33Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, Bethesda, Maryland, USA
Alexander J. Mentzer
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
3Big Data Institute, Li Ka Shing Centre for Health and Information Discovery, Old Road Campus, Oxford OX3 7LF
Gil McVean
3Big Data Institute, Li Ka Shing Centre for Health and Information Discovery, Old Road Campus, Oxford OX3 7LF
Kalifa A. Bojang
4Medical Research Council Unit, Atlantic Boulevard, Serrekunda, The Gambia
Ogobara Doumbo
7Malaria Research and Training Centre, Faculty of Medicine, University of Bamako, Bamako, Mali
David Modiano
8University of Rome La Sapienza, Italy
Kwadwo A. Koram
11Noguchi Memorial Institute for Medical Research, Accra, Ghana
Tsiri Agbenyega
12Komfo Anokye Teaching Hospital, Kumasi, Ghana
13Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Olukemi K. Amodu
16Institute of Child Health, College of Medicine, University of Ibadan, Nigeria
Eric Achidi
34Department of Medical Laboratory Sciences, University of Buea, Buea, South West Region, Cameroon
Thomas N. Williams
18KEMRI-Wellcome Trust Research Programme, PO Box 230, Kilifi, Kenya
35Faculty of Medicine, Department of Medicine, Imperial College, Exhibition Road, London SW7 2AZ, UK
Kevin Marsh
18KEMRI-Wellcome Trust Research Programme, PO Box 230, Kilifi, Kenya
36Nuffield Department of Medicine, NDM Research Building, Roosevelt Drive, Headington, Oxford OX3 7FZ
Eleanor M. Riley
6Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK
37The Roslin Institute, The University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG
Malcolm Molyneux
38Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, PO Box 30096, Blantyre, Malawi
Terrie Taylor
39Blantyre Malaria Project, College of Medicine, University of Malawi
40College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824, USA
Sarah J. Dunstan
41Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Australia
Jeremy Farrar
21Oxford University Clinical Research Unit, 764 Vo Van Kiet, District 5, Ho Chi Minh City, VietNam
42Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, OX3 7LJ, UK
Ivo Mueller
24Papua New Guinea Institute of Medical Research, PO Box 60, Garoka, EHP441, PNG
27The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
43Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain
Kirk A. Rockett
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
2Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
Dominic P. Kwiatkowski
1Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
2Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
3Big Data Institute, Li Ka Shing Centre for Health and Information Discovery, Old Road Campus, Oxford OX3 7LF
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.
Footnotes
- Update to authors, affiliations, data availability statement - Include missing supplementary text sections
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Posted October 14, 2019.
New insights into malaria susceptibility from the genomes of 17,000 individuals from Africa, Asia, and Oceania
Malaria Genomic Epidemiology Network, 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, Steve 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
bioRxiv 535898; doi: https://doi.org/10.1101/535898
New insights into malaria susceptibility from the genomes of 17,000 individuals from Africa, Asia, and Oceania
Malaria Genomic Epidemiology Network, 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, Steve 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
bioRxiv 535898; doi: https://doi.org/10.1101/535898
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