34 results on '"Ndila, Carolyne M."'
Search Results
2. Glucose-6-phosphate dehydrogenase deficiency and susceptibility to childhood diseases in Kilifi, Kenya
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Uyoga, Sophie, Macharia, Alex W., Ndila, Carolyne M., Nyutu, Gideon, Shebe, Mohammed, Awuondo, Kennedy O., Mturi, Neema, Peshu, Norbert, Tsofa, Benjamin, Scott, J. Anthony G., Maitland, Kathryn, and Williams, Thomas N.
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- 2020
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3. The epidemiology of sickle cell disease in children recruited in infancy in Kilifi, Kenya: a prospective cohort study
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Uyoga, Sophie, Macharia, Alex W, Mochamah, George, Ndila, Carolyne M, Nyutu, Gideon, Makale, Johnstone, Tendwa, Metrine, Nyatichi, Emily, Ojal, John, Otiende, Mark, Shebe, Mohammed, Awuondo, Kennedy O, Mturi, Neema, Peshu, Norbert, Tsofa, Benjamin, Maitland, Kathryn, Scott, J Anthony G, and Williams, Thomas N
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- 2019
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4. Non-O ABO blood group genotypes differ in their associations with Plasmodium falciparum rosetting and severe malaria
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Opi, D. Herbert, primary, Ndila, Carolyne M., additional, Uyoga, Sophie, additional, Macharia, Alex W., additional, Fennell, Clare, additional, Ochola, Lucy B., additional, Nyutu, Gideon, additional, Siddondo, Bethseba R., additional, Ojal, John, additional, Shebe, Mohammed, additional, Awuondo, Kennedy O., additional, Mturi, Neema, additional, Peshu, Norbert, additional, Tsofa, Benjamin, additional, Band, Gavin, additional, Maitland, Kathryn, additional, Kwiatkowski, Dominic P., additional, Rockett, Kirk A., additional, Williams, Thomas N., additional, and Rowe, J. Alexandra, additional
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- 2023
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5. Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study
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Abathina, Amadou, Abubakar, Ismaela, Achidi, Eric, Agbenyega, Tsiri, Aiyegbo, Mohammed, Akoto, Alex, Allen, Angela, Allen, Stephen, Amenga-Etego, Lucas, Amodu, Folakemi, Amodu, Olukemi, Anchang-Kimbi, Judith, Ansah, Nana, Ansah, Patrick, Ansong, Daniel, Antwi, Sampson, Anyorigiya, Thomas, Apinjoh, Tobias, Asafo-Agyei, Emmanuel, Asoala, Victor, Atuguba, Frank, Auburn, Sarah, Bah, Abdou, Bamba, Kariatou, Bancone, Germana, Band, Gavin, Barnwell, David, Barry, Abdoulaye, Bauni, Evasius, Besingi, Richard, Bojang, Kalifa, Bougouma, Edith, Bull, Susan, Busby, George, Camara, Abdoulie, Camara, Landing, Campino, Susana, Carter, Richard, Carucci, Dan, Casals-Pascual, Climent, Ceesay, Ndey, Ceesay, Pa, Chau, Tran, Chuong, Ly, Clark, Taane, Clarke, Geraldine, Cole-Ceesay, Ramou, Conway, David, Cook, Katharine, Cook, Olivia, Cornelius, Victoria, Corran, Patrick, Correa, Simon, Cox, Sharon, Craik, Rachel, Danso, Bakary, Davis, Timothy, Day, Nicholas, Deloukas, Panos, Dembele, Awa, deVries, Jantina, Dewasurendra, Rajika, Diakite, Mahamadou, Diarra, Elizabeth, Dibba, Yaya, Diss, Andrea, Djimdé, Abdoulaye, Dolo, Amagana, Doumbo, Ogobara, Doyle, Alan, Drakeley, Chris, Drury, Eleanor, Duffy, Patrick, Dunstan, Sarah, Ebonyi, Augustine, Elhassan, Ahmed, Elhassan, Ibrahim, Elzein, Abier, Enimil, Anthony, Esangbedo, Pamela, Evans, Jennifer, Evans, Julie, Farrar, Jeremy, Fernando, Deepika, Fitzpatrick, Kathryn, Fullah, Janet, Garcia, Jacob, Ghansah, Anita, Gottleib, Michael, Green, Angie, Hart, Lee, Hennsman, Meike, Hien, Tran, Hieu, Nguyen, Hilton, Eliza, Hodgson, Abraham, Horstmann, Rolf, Hubbart, Christina, Hughes, Catherine, Hussein, Ayman, Hutton, Robert, Ibrahim, Muntaser, Ishengoma, Deus, Jaiteh, Jula, Jallow, Mariatou, Jallow, Muminatou, Jammeh, Kebba, Jasseh, Momodou, Jeffreys, Anna, Jobarteh, Amie, Johnson, Kimberly, Joseph, Sarah, Jyothi, Dushyanth, Kachala, David, Kamuya, Dorcas, Kanyi, Haddy, Karunajeewa, Harin, Karunaweera, Nadira, Keita, Momodou, Kerasidou, Angeliki, Khan, Aja, Kivinen, Katja, Kokwaro, Gilbert, Konate, Amadou, Konate, Salimata, Koram, Kwadwo, Kwiatkowski, Dominic, Laman, Moses, Le, Si, Leffler, Ellen, Lemnge, Martha, Lin, Enmoore, Ly, Alioune, Macharia, Alexander, MacInnis, Bronwyn, Mai, Nguyen, Makani, Julie, Malangone, Cinzia, Mangano, Valentina, Manjurano, Alphaxard, Manneh, Lamin, Manning, Laurens, Manske, Magnus, Marsh, Kevin, Marsh, Vicki, Maslen, Gareth, Maxwell, Caroline, Mbunwe, Eric, McCreight, Marilyn, Mead, Daniel, Mendy, Alieu, Mendy, Anthony, Mensah, Nathan, Michon, Pascal, Miles, Alistair, Miotto, Olivo, Modiano, David, Mohamed, Hiba, Molloy, Sile, Molyneux, Malcolm, Molyneux, Sassy, Moore, Mike, Moyes, Catherine, Mtei, Frank, Mtove, George, Mueller, Ivo, Mugri, Regina, Munthali, Annie, Mutabingwa, Theonest, Nadjm, Behzad, Ndi, Andre, Ndila, Carolyne, Newton, Charles, Niangaly, Amadou, Njie, Haddy, Njie, Jalimory, Njie, Madi, Njie, Malick, Njie, Sophie, Njiragoma, Labes, Nkrumah, Francis, Ntunthama, Neema, Nyika, Aceme, Nyirongo, Vysaul, O'Brien, John, Obu, Herbert, Oduro, Abraham, Ofori, Alex, Olaniyan, Subulade, Olaosebikan, Rasaq, Oluoch, Tom, Omotade, Olayemi, Oni, Olajumoke, Onykwelu, Emmanuel, Opi, Daniel, Orimadegun, Adebola, O'Riordan, Sean, Ouedraogo, Issa, Oyola, Samuel, Parker, Michael, Pearson, Richard, Pensulo, Paul, Peshu, Norbert, Phiri, Ajib, Phu, Nguyen, Pinder, Margaret, Pirinen, Matti, Plowe, Chris, Potter, Claire, Poudiougou, Belco, Puijalon, Odile, Quyen, Nguyen, Ragoussis, Ioannis, Ragoussis, Jiannis, Rasheed, Oba, Reeder, John, Reyburn, Hugh, Riley, Eleanor, Risley, Paul, Rockett, Kirk, Rodford, Joanne, Rogers, Jane, Rogers, William, Rowlands, Kate, Ruano-Rubio, Valentín, Sabally-Ceesay, Kumba, Sadiq, Abubacar, Saidy-Khan, Momodou, Saine, Horeja, Sakuntabhai, Anavaj, Sall, Abdourahmane, Sambian, David, Sambou, Idrissa, SanJoaquin, Miguel, Sepúlveda, Nuno, Shah, Shivang, Shelton, Jennifer, Siba, Peter, Silva, Nilupa, Simmons, Cameron, Simpore, Jaques, Singhasivanon, Pratap, Sinh, Dinh, Sirima, Sodiomon, Sirugo, Giorgio, Sisay-Joof, Fatoumatta, Sissoko, Sibiry, Small, Kerrin, Somaskantharajah, Elilan, Spencer, Chris, Stalker, Jim, Stevens, Marryat, Suriyaphol, Prapat, Sylverken, Justice, Taal, Bintou, Tall, Adama, Taylor, Terrie, Teo, Yik, Thai, Cao, Thera, Mahamadou, Titanji, Vincent, Toure, Ousmane, Troye-Blomberg, Marita, Usen, Stanley, Uyoga, Sophie, Vanderwal, Aaron, Wangai, Hannah, Watson, Renee, Williams, Thomas, Wilson, Michael, Wrigley, Rebecca, Yafi, Clarisse, Yamoah, Lawrence, Ndila, Carolyne M, Macharia, Alexander W, Nyutu, Gideon, Ojal, John, Shebe, Mohammed, Awuondo, Kennedy O, Mturi, Neema, Tsofa, Benjamin, Clark, Taane G, Kariuki, Silvia, Mackinnon, Margaret, Maitland, Kathryn, Kwiatkowski, Dominic P, Rockett, Kirk A, and Williams, Thomas N
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- 2018
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6. Resistance to malaria through structural variation of red blood cell invasion receptors
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Malaria Genomic Epidemiology Network, Leffler, Ellen M., Band, Gavin, Busby, George B. J., Kivinen, Katja, Le, Quang Si, Clarke, Geraldine M., Bojang, Kalifa A., Conway, David J., Jallow, Muminatou, Sisay-Joof, Fatoumatta, Bougouma, Edith C., Mangano, Valentina D., Modiano, David, Sirima, Sodiomon B., Achidi, Eric, Apinjoh, Tobias O., Marsh, Kevin, Ndila, Carolyne M., Peshu, Norbert, Williams, Thomas N., Drakeley, Chris, Manjurano, Alphaxard, Reyburn, Hugh, Riley, Eleanor, Kachala, David, Molyneux, Malcolm, Nyirongo, Vysaul, Taylor, Terrie, Thornton, Nicole, Tilley, Louise, Grimsley, Shane, Drury, Eleanor, Stalker, Jim, Cornelius, Victoria, Hubbart, Christina, Jeffreys, Anna E., Rowlands, Kate, Rockett, Kirk A., Spencer, Chris C. A., and Kwiatkowski, Dominic P.
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- 2017
7. The clinical spectrum of severe childhood malaria in Eastern Uganda
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Olupot-Olupot, Peter, Engoru, Charles, Nteziyaremye, Julius, Chebet, Martin, Ssenyondo, Tonny, Muhindo, Rita, Nyutu, Gideon, Macharia, Alexander W., Uyoga, Sophie, Ndila, Carolyne M., Karamagi, Charles, Maitland, Kathryn, and Williams, Thomas N.
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- 2020
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8. The indirect health effects of malaria estimated from health advantages of the sickle cell trait
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Uyoga, Sophie, Macharia, Alex W., Ndila, Carolyne M., Nyutu, Gideon, Shebe, Mohammed, Awuondo, Kennedy O., Mturi, Neema, Peshu, Norbert, Tsofa, Benjamin, Scott, J. Anthony G., Maitland, Kathryn, and Williams, Thomas N.
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- 2019
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9. Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study
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Uyoga, Sophie, Ndila, Carolyne M, Macharia, Alex W, Nyutu, Gideon, Shah, Shivang, Peshu, Norbert, Clarke, Geraldine M, Kwiatkowski, Dominic P, Rockett, Kirk A, and Williams, Thomas N
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- 2015
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10. Non-O ABO blood group genotypes differ in their associations with Plasmodium falciparum rosetting and severe malaria
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Opi, D. Herbert, primary, Ndila, Carolyne M, additional, Uyoga, Sophie, additional, Macharia, Alex W, additional, Fennell, Clare, additional, Nyutu, Gideon, additional, Ojal, John, additional, Shebe, Mohammed, additional, Awuondo, Kennedy O, additional, Mturi, Neema, additional, Peshu, Norbert, additional, Tsofa, Benjamin, additional, Band, Gavin, additional, Maitland, Kathryn, additional, Kwiatkowski, Dominic P, additional, Rockett, Kirk A, additional, Williams, Thomas N., additional, and Rowe, J. Alexandra, additional
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- 2022
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11. The clinical epidemiology of sickle cell anemia In Africa
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Macharia, Alex W., Mochamah, George, Uyoga, Sophie, Ndila, Carolyne M., Nyutu, Gideon, Makale, Johnstone, Tendwa, Metrine, Nyatichi, Emily, Ojal, John, Shebe, Mohammed, Awuondo, Kennedy O., Mturi, Neema, Peshu, Norbert, Tsofa, Benjamin, Scott, J. Anthony G., Maitland, Kathryn, and Williams, Thomas N.
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- 2018
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12. BIRC6 modifies risk of invasive bacterial infection in Kenyan children
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Gilchrist, James J, primary, Kariuki, Silvia N, additional, Watson, James A, additional, Band, Gavin, additional, Uyoga, Sophie, additional, Ndila, Carolyne M, additional, Mturi, Neema, additional, Mwarumba, Salim, additional, Mohammed, Shebe, additional, Mosobo, Moses, additional, Alasoo, Kaur, additional, Rockett, Kirk A, additional, Mentzer, Alexander J, additional, Kwiatkowski, Dominic P, additional, Hill, Adrian VS, additional, Maitland, Kathryn, additional, Scott, J Anthony G, additional, and Williams, Thomas N, additional
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- 2022
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13. Author response: BIRC6 modifies risk of invasive bacterial infection in Kenyan children
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Gilchrist, James J, primary, Kariuki, Silvia N, additional, Watson, James A, additional, Band, Gavin, additional, Uyoga, Sophie, additional, Ndila, Carolyne M, additional, Mturi, Neema, additional, Mwarumba, Salim, additional, Mohammed, Shebe, additional, Mosobo, Moses, additional, Alasoo, Kaur, additional, Rockett, Kirk A, additional, Mentzer, Alexander J, additional, Kwiatkowski, Dominic P, additional, Hill, Adrian VS, additional, Maitland, Kathryn, additional, Scott, J Anthony G, additional, and Williams, Thomas N, additional
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- 2022
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14. Malaria protection due to sickle haemoglobin depends on parasite genotype
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Band, Gavin, primary, Leffler, Ellen M., additional, Jallow, Muminatou, additional, Sisay-Joof, Fatoumatta, additional, Ndila, Carolyne M., additional, Macharia, Alexander W., additional, Hubbart, Christina, additional, Jeffreys, Anna E., additional, Rowlands, Kate, additional, Nguyen, Thuy, additional, Gonçalves, Sónia, additional, Ariani, Cristina V., additional, Stalker, Jim, additional, Pearson, Richard D., additional, Amato, Roberto, additional, Drury, Eleanor, additional, Sirugo, Giorgio, additional, d’Alessandro, Umberto, additional, Bojang, Kalifa A., additional, Marsh, Kevin, additional, Peshu, Norbert, additional, Saelens, Joseph W., additional, Diakité, Mahamadou, additional, Taylor, Steve M., additional, Conway, David J., additional, Williams, Thomas N., additional, Rockett, Kirk A., additional, and Kwiatkowski, Dominic P., additional
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- 2021
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15. A novel locus of resistance to severe malaria in a region of ancient balancing selection
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Band, Gavin, Rockett, Kirk A., Spencer, Chris C.A., Kwiatkowski, Dominic P., Le, Quang Si, Clarke, Geraldine M., Kivinen, Katja, Leffler, Ellen M., Cornelius, Victoria, Conway, David J., Williams, Thomas N., Taylor, Terrie, Bojang, Kalifa A., Doumbo, Ogobara, Thera, Mahamadou A., Modiano, David, Sirima, Sodiomon B., Wilson, Michael D., Koram, Kwadwo A., Agbenyega, Tsiri, Achidi, Eric, Marsh, Kevin, Reyburn, Hugh, Drakeley, Chris, Riley, Eleanor, Molyneux, Malcolm, Jallow, Muminatou, Pinder, Margaret, Toure, Ousmane B., Konate, Salimata, Sissoko, Sibiri, Bougouma, Edith C., Mangano, Valentina D., Amenga-Etego, Lucas N., Ghansah, Anita K., Hodgson, Abraham V.O., Ansong, Daniel, Enimil, Anthony, Evans, Jennifer, Apinjoh, Tobias O., Macharia, Alexander, Ndila, Carolyne M., Newton, Charles, Peshu, Norbert, Uyoga, Sophie, Manjurano, Alphaxard, Kachala, David, Nyirongo, Vysaul, Mead, Daniel, Drury, Eleanor, Auburn, Sarah, Campino, Susana G., MacInnis, Bronwyn, Stalker, Jim, Gray, Emma, Hubbart, Christina, Jeffreys, Anna E., Rowlands, Kate, Mendy, Alieu, Craik, Rachel, Fitzpatrick, Kathryn, Molloy, Sile, Hart, Lee, Hutton, Robert, Kerasidou, Angeliki, and Johnson, Kimberly J.
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- 2015
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16. Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision
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Watson, James A, primary, Ndila, Carolyne M, primary, Uyoga, Sophie, additional, Macharia, Alexander, additional, Nyutu, Gideon, additional, Mohammed, Shebe, additional, Ngetsa, Caroline, additional, Mturi, Neema, additional, Peshu, Norbert, additional, Tsofa, Benjamin, additional, Rockett, Kirk, additional, Leopold, Stije, additional, Kingston, Hugh, additional, George, Elizabeth C, additional, Maitland, Kathryn, additional, Day, Nicholas PJ, additional, Dondorp, Arjen M, additional, Bejon, Philip, additional, Williams, Thomas N, additional, Holmes, Chris C, additional, and White, Nicholas J, additional
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- 2021
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17. Author response: Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision
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Watson, James A, primary, Ndila, Carolyne M, additional, Uyoga, Sophie, additional, Macharia, Alexander, additional, Nyutu, Gideon, additional, Mohammed, Shebe, additional, Ngetsa, Caroline, additional, Mturi, Neema, additional, Peshu, Norbert, additional, Tsofa, Benjamin, additional, Rockett, Kirk, additional, Leopold, Stije, additional, Kingston, Hugh, additional, George, Elizabeth C, additional, Maitland, Kathryn, additional, Day, Nicholas PJ, additional, Dondorp, Arjen M, additional, Bejon, Philip, additional, Williams, Thomas, additional, Holmes, Chris C, additional, and White, Nicholas J, additional
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- 2021
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18. The protective effect of sickle cell haemoglobin against severe malaria depends on parasite genotype
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Band, Gavin, primary, Leffler, Ellen M., additional, Jallow, Muminatou, additional, Sisay-Joof, Fatoumatta, additional, Ndila, Carolyne M., additional, Macharia, Alexander W., additional, Hubbart, Christina, additional, Jeffreys, Anna E., additional, Rowlands, Kate, additional, Nguyen, Thuy, additional, Goncalves, Sonia M., additional, Ariani, Cristina V., additional, Stalker, Jim, additional, Pearson, Richard D., additional, Amato, Roberto, additional, Drury, Eleanor, additional, Sirugo, Giorgio, additional, D’Alessandro, Umberto, additional, Bojang, Kalifa A., additional, Marsh, Kevin, additional, Peshu, Norbert, additional, Conway, David J., additional, Williams, Thomas N., additional, Rockett, Kirk A., additional, and Kwiatkowski, Dominic P., additional
- Published
- 2021
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19. 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, 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., Kwiatkowski, Dominic P., HUS Gynecology and Obstetrics, and Wellcome Trust
- Subjects
0301 basic medicine ,Male ,RESISTANCE LOCI ,General Physics and Astronomy ,Datasets as Topic ,Genome-wide association study ,Disease ,Genome-wide association studies ,DISEASE ,0302 clinical medicine ,HLA Antigens ,BLOOD-GROUP ,Prevalence ,qu_460 ,Malaria, Falciparum ,Child ,lcsh:Science ,GENE-EXPRESSION ,11832 Microbiology and virology ,Genetics ,Multidisciplinary ,PLASMODIUM-FALCIPARUM ,biology ,GENOTYPE ,3. Good health ,ALLELE ,Cerebral Malaria ,Chromosomes, Human, Pair 6 ,Female ,Malaria Genomic Epidemiology Network ,Medical genomics ,Adult ,Asia ,Science ,Oceania ,wa_395 ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Article ,malaria genomic epidemiology ,plasmodium-falciparum ,genotype ,03 medical and health sciences ,Plasma Membrane Calcium-Transporting ATPases ,parasitic diseases ,medicine ,Immunogenetics ,Humans ,Genetic Predisposition to Disease ,Genetic association ,TRANSCRIPTOME ANALYSES ,IDENTIFICATION ,Case-control study ,Plasmodium falciparum ,wc_755 ,General Chemistry ,biology.organism_classification ,medicine.disease ,wc_750 ,Malaria ,ASSOCIATION ANALYSIS ,030104 developmental biology ,Infectious disease (medical specialty) ,Genetic Loci ,Case-Control Studies ,Africa ,lcsh:Q ,3111 Biomedicine ,030217 neurology & neurosurgery ,Genome-Wide Association Study - 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., Four genome-wide associated loci are currently known for malaria susceptibility. Here, the authors expand on earlier work by combining data from 11 malaria-endemic countries and additional population sequencing informing an African-enriched imputation reference panel, with findings including a previously unreported association on chromosome 6.
- Published
- 2019
20. β‐Thalassemia pathogenic variants in a cohort of children from the East African coast
- Author
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Macharia, Alexander W., primary, Mochamah, George, additional, Uyoga, Sophie, additional, Ndila, Carolyne M., additional, Nyutu, Gideon, additional, Tendwa, Metrine, additional, Nyatichi, Emily, additional, Makale, Johnstone, additional, Ware, Russell E., additional, and Williams, Thomas N., additional
- Published
- 2020
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21. A global network for investigating the genomic epidemiology of malaria
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Achidi, Eric Akum, Agbenyega, Tsiri, Allen, Stephen, Amodu, Olukemi, Bojang, Kalifa, Conway, David, Corran, Patrick, Deloukas, Panos, Djimde, Abdoulaye, Dolo, Amagana, Doumbo, Ogobara, Drakeley, Chris, Duffy, Patrick, Dunstan, Sarah, Evans, Jennifer, Farrar, Jeremy, Fernando, Deepika, Hien, Tran Tinh, Horstmann, Rolf, Ibrahim, Muntaser, Karunaweera, Nadira, Kokwaro, Gilbert, Koram, Kojo, Kwiatkowski, Dominic, Lemnge, Martha, Makani, Julie, Marsh, Kevin, Michon, Pascal, Modiano, David, Molyneux, Malcolm E., Mueller, Ivo, Mutabingwa, Theonest, Peshu, Norbert, Plowe, Chris, Puijalon, Odile, Ragoussis, Jiannis, Reeder, John, Reyburn, Hugh, Riley, Eleanor, Rogers, Jane, Sakuntabhai, Anavaj, Singhasivanon, Pratap, Sirima, Sodiomon, Sirugo, Giorgio, Tall, Adama, Taylor, Terrie, Thera, Mahamadou, Troye-Blomberg, Marita, Williams, Tom, Wilson, Michael, Amenga-Etego, Lucas, Apinjoh, Tobias O., Bougouma, Edith, Dewasurendra, Rajika, Diakite, Mahamadou, Enimil, Anthony, Hussein, Ayman, Ishengoma, Deus, Jallow, Muminatou, Lin, Enmoore, Ly, Alioune, Mangano, Valentina D., Manjurano, Alphaxard, Manning, Laurens, Ndila, Carolyne M., Nyirongo, Vysaul, Oluoch, Tom, Quyen, Nguyen T. N., Suriyaphol, Prapat, Toure, Ousman, Kwiatkowski, Dominic, Alcock, Daniel, Auburn, Sarah, Barnwell, David, Bull, Susan, Campino, Susana, deVries, Jantina, Elzein, Abier, Evans, Julie, Fitzpatrick, Kathryn, Ghansah, Anita, Green, Angie, Hart, Lee, Hilton, Eliza, Hubbart, Christina, Hughes, Catherine, Jeffreys, Anna E., Kivinen, Katja, MacInnis, Bronwyn, Manske, Magnus, Maslen, Gareth, McCreight, Marilyn, Mendy, Alieu, Moyes, Catherine, Nyika, Aceme, Potter, Claire, Risley, Paul, Rowlands, Kate, SanJoaquin, Miguel, Small, Kerrin, Somaskantharajah, Elilan, Stevens, Marryat, Teo, YikYing, Watson, Renee, Carucci, Dan, Cook, Katharine, Doyle, Alan, Duombo, Ogobara, Gottlieb, Michael, Kwiatkowski, Dominic, Rockett, Kirk A., Vanderwal, Aaron, Clark, Taane, Parker, Michael, and Wrigley, Rebecca
- Published
- 2008
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22. Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study
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Ndila, Carolyne M, Uyoga, Sophie, Macharia, Alexander W, Nyutu, Gideon, Peshu, Norbert, Ojal, John, Shebe, Mohammed, Awuondo, Kennedy O, Mturi, Neema, Tsofa, Benjamin, Sepúlveda, Nuno, Clark, Taane G, Band, Gavin, Clarke, Geraldine, Rowlands, Kate, Hubbart, Christina, Jeffreys, Anna, Kariuki, Silvia, Marsh, Kevin, Mackinnon, Margaret, Maitland, Kathryn, Kwiatkowski, Dominic P, Rockett, Kirk A, Williams, Thomas N, Abathina, Amadou, Abubakar, Ismaela, Achidi, Eric, Agbenyega, Tsiri, Aiyegbo, Mohammed, Akoto, Alex, Allen, Angela, Allen, Stephen, Amenga-Etego, Lucas, Amodu, Folakemi, Amodu, Olukemi, Anchang-Kimbi, Judith, Ansah, Nana, Ansah, Patrick, Ansong, Daniel, Antwi, Sampson, Anyorigiya, Thomas, Apinjoh, Tobias, Asafo-Agyei, Emmanuel, Asoala, Victor, Atuguba, Frank, Auburn, Sarah, Bah, Abdou, Bamba, Kariatou, Bancone, Germana, Barnwell, David, Barry, Abdoulaye, Bauni, Evasius, Besingi, Richard, Bojang, Kalifa, Bougouma, Edith, Bull, Susan, Busby, George, Camara, Abdoulie, Camara, Landing, Campino, Susana, Carter, Richard, Carucci, Dan, Casals-Pascual, Climent, Ceesay, Ndey, Ceesay, Pa, Chau, Tran, Chuong, Ly, Clark, Taane, Cole-Ceesay, Ramou, Conway, David, Cook, Katharine, Cook, Olivia, Cornelius, Victoria, Corran, Patrick, Correa, Simon, Cox, Sharon, Craik, Rachel, Danso, Bakary, Davis, Timothy, Day, Nicholas, Deloukas, Panos, Dembele, Awa, Devries, Jantina, Dewasurendra, Rajika, Diakite, Mahamadou, Diarra, Elizabeth, Dibba, Yaya, Diss, Andrea, Djimdé, Abdoulaye, Dolo, Amagana, Doumbo, Ogobara, Doyle, Alan, Drakeley, Chris, Drury, Eleanor, Duffy, Patrick, Dunstan, Sarah, Ebonyi, Augustine, Elhassan, Ahmed, Elhassan, Ibrahim, Elzein, Abier, Enimil, Anthony, Esangbedo, Pamela, Evans, Jennifer, Evans, Julie, Farrar, Jeremy, Fernando, Deepika, Fitzpatrick, Kathryn, Fullah, Janet, Garcia, Jacob, Ghansah, Anita, Gottleib, Michael, Green, Angie, Hart, Lee, Hennsman, Meike, Hien, Tran, Hieu, Nguyen, Hilton, Eliza, Hodgson, Abraham, Horstmann, Rolf, Hughes, Catherine, Hussein, Ayman, Hutton, Robert, Ibrahim, Muntaser, Ishengoma, Deus, Jaiteh, Jula, Jallow, Mariatou, Jallow, Muminatou, Jammeh, Kebba, Jasseh, Momodou, Jobarteh, Amie, Johnson, Kimberly, Joseph, Sarah, Jyothi, Dushyanth, Kachala, David, Kamuya, Dorcas, Kanyi, Haddy, Karunajeewa, Harin, Karunaweera, Nadira, Keita, Momodou, Kerasidou, Angeliki, Khan, Aja, Kivinen, Katja, Kokwaro, Gilbert, Konate, Amadou, Konate, Salimata, Koram, Kwadwo, Kwiatkowski, Dominic, Laman, Moses, Si, Le, Leffler, Ellen, Lemnge, Martha, Lin, Enmoore, Alioune, Ly, Macharia, Alexander, Macinnis, Bronwyn, Mai, Nguyen, Makani, Julie, Malangone, Cinzia, Mangano, Valentina, Manjurano, Alphaxard, Manneh, Lamin, Manning, Laurens, Manske, Magnus, Marsh, Vicki, Maslen, Gareth, Maxwell, Caroline, Mbunwe, Eric, Mccreight, Marilyn, Mead, Daniel, Mendy, Alieu, Mendy, Anthony, Mensah, Nathan, Michon, Pascal, Miles, Alistair, Miotto, Olivo, Modiano, David, Mohamed, Hiba, Molloy, Sile, Molyneux, Malcolm, Molyneux, Sassy, Moore, Mike, Moyes, Catherine, Mtei, Frank, Mtove, George, Mueller, Ivo, Mugri, Regina, Munthali, Annie, Mutabingwa, Theonest, Nadjm, Behzad, Ndi, Andre, Ndila, Carolyne, Newton, Charles, Niangaly, Amadou, Njie, Haddy, Njie, Jalimory, Njie, Madi, Njie, Malick, Njie, Sophie, Njiragoma, Labes, Nkrumah, Francis, Ntunthama, Neema, Nyika, Aceme, Nyirongo, Vysaul, O'Brien, John, Obu, Herbert, Oduro, Abraham, Ofori, Alex, Olaniyan, Subulade, Olaosebikan, Rasaq, Oluoch, Tom, Omotade, Olayemi, Oni, Olajumoke, Onykwelu, Emmanuel, Opi, Daniel, Orimadegun, Adebola, O'Riordan, Sean, Ouedraogo, Issa, Oyola, Samuel, Parker, Michael, Pearson, Richard, Pensulo, Paul, Phiri, Ajib, Phu, Nguyen, Pinder, Margaret, Pirinen, Matti, Plowe, Chris, Potter, Claire, Poudiougou, Belco, Puijalon, Odile, Quyen, Nguyen, Ragoussis, Ioannis, Ragoussis, Jiannis, Rasheed, Oba, Reeder, John, Reyburn, Hugh, Riley, Eleanor, Risley, Paul, Rockett, Kirk, Rodford, Joanne, Rogers, Jane, Rogers, William, Ruano-Rubio, Valentín, Sabally-Ceesay, Kumba, Sadiq, Abubacar, Saidy-Khan, Momodou, Saine, Horeja, Sakuntabhai, Anavaj, Sall, Abdourahmane, Sambian, David, Sambou, Idrissa, Sanjoaquin, Miguel, Shah, Shivang, Shelton, Jennifer, Siba, Peter, Silva, Nilupa, Simmons, Cameron, Simpore, Jaques, Singhasivanon, Pratap, Sinh, Dinh, Sirima, Sodiomon, Sirugo, Giorgio, Sisay-Joof, Fatoumatta, Sissoko, Sibiry, Small, Kerrin, Somaskantharajah, Elilan, Spencer, Chris, Stalker, Jim, Stevens, Marryat, Suriyaphol, Prapat, Sylverken, Justice, Taal, Bintou, Tall, Adama, Taylor, Terrie, Teo, Yik, Thai, Cao, Thera, Mahamadou, Titanji, Vincent, Toure, Ousmane, Troye-Blomberg, Marita, Usen, Stanley, Vanderwal, Aaron, Wangai, Hannah, Watson, Renee, Williams, Thomas, Wilson, Michael, Wrigley, Rebecca, Yafi, Clarisse, Yamoah, Lawrence, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, London School of Hygiene and Tropical Medicine (LSHTM), The Wellcome Trust Sanger Institute [Cambridge], St Mary's Hospital, Imperial College, TNW and MM are funded through awards from the Wellcome Trust (grants 091758 and 202800 [to TNW] and grant 088634 [to MM]) and DPK and TGC receive support from the Medical Research Council (grant G19/9 [to DPK] and grants MR/K000551/1, MR/M01360X/1, MR/N010469/1, and MC_PC_15103 [to TGC]). The research leading to these results received funding from the European Community's Seventh Framework Programme (FP7/2007-2013, under grant agreement 242095) and from the Medical Research Council (grant G0600718). MalariaGEN is supported by the Wellcome Trust (WT077383/Z/05/Z) and by the Foundation for the National Institutes of Health (grant 566) as part of the Bill & Melinda Gates' Grand Challenges in Global Health Initiative. The Resource Centre for Genomic Epidemiology of Malaria is supported by the Wellcome Trust (grant 090770/Z/09/Z). Support was also provided by the Medical Research Council (grant G0600718). The Wellcome Trust also provides core awards to the Wellcome Trust Centre for Human Genetics (grant 090532/Z/09/Z) and to the Wellcome Trust Sanger Institute (grant 098051). This work forms part of a larger collaboration with the MalariaGEN Consortium, whose members are listed at http://www.malariagen.net/projects/host/consortium-members. This paper is published with permission from the Director of the Kenya Medical Research Institute (KEMRI)., MalariaGEN Consortium (Anavaj Sakuntabhai), and European Project: 242095,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,EVIMALAR(2009)
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Case-Control Studies ,Child ,Child, Preschool ,Female ,Gene Frequency ,Genetic Predisposition to Disease ,Humans ,Kenya ,Malaria ,Male ,Polymorphism, Genetic ,Hematology ,macromolecular substances ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,Article ,Genetic ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,parasitic diseases ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Polymorphism ,Preschool - Abstract
Summary Background Human genetic factors are important determinants of malaria risk. We investigated associations between multiple candidate polymorphisms—many related to the structure or function of red blood cells—and risk for severe Plasmodium falciparum malaria and its specific phenotypes, including cerebral malaria, severe malaria anaemia, and respiratory distress. Methods We did a case-control study in Kilifi County, Kenya. We recruited as cases children presenting with severe malaria to the high-dependency ward of Kilifi County Hospital. We included as controls infants born in the local community between Aug 1, 2006, and Sept 30, 2010, who were part of a genetics study. We tested for associations between a range of candidate malaria-protective genes and risk for severe malaria and its specific phenotypes. We used a permutation approach to account for multiple comparisons between polymorphisms and severe malaria. We judged p values less than 0·005 significant for the primary analysis of the association between candidate genes and severe malaria. Findings Between June 11, 1995, and June 12, 2008, 2244 children with severe malaria were recruited to the study, and 3949 infants were included as controls. Overall, 263 (12%) of 2244 children with severe malaria died in hospital, including 196 (16%) of 1233 with cerebral malaria. We investigated 121 polymorphisms in 70 candidate severe malaria-associated genes. We found significant associations between risk for severe malaria overall and polymorphisms in 15 genes or locations, of which most were related to red blood cells: ABO, ATP2B4, ARL14, CD40LG, FREM3, INPP4B, G6PD, HBA (both HBA1 and HBA2), HBB, IL10, LPHN2 (also known as ADGRL2), LOC727982, RPS6KL1, CAND1, and GNAS. Combined, these genetic associations accounted for 5·2% of the variance in risk for developing severe malaria among individuals in the general population. We confirmed established associations between severe malaria and sickle-cell trait (odds ratio [OR] 0·15, 95% CI 0·11–0·20; p=2·61 × 10−58), blood group O (0·74, 0·66–0·82; p=6·26 × 10−8), and –α3·7-thalassaemia (0·83, 0·76–0·90; p=2·06 × 10−6). We also found strong associations between overall risk of severe malaria and polymorphisms in both ATP2B4 (OR 0·76, 95% CI 0·63–0·92; p=0·001) and FREM3 (0·64, 0·53–0·79; p=3·18 × 10−14). The association with FREM3 could be accounted for by linkage disequilibrium with a complex structural mutation within the glycophorin gene region (comprising GYPA, GYPB, and GYPE) that encodes for the rare Dantu blood group antigen. Heterozygosity for Dantu was associated with risk for severe malaria (OR 0·57, 95% CI 0·49–0·68; p=3·22 × 10−11), as was homozygosity (0·26, 0·11–0·62; p=0·002). Interpretation Both ATP2B4 and the Dantu blood group antigen are associated with the structure and function of red blood cells. ATP2B4 codes for plasma membrane calcium-transporting ATPase 4 (the major calcium pump on red blood cells) and the glycophorins are ligands for parasites to invade red blood cells. Future work should aim at uncovering the mechanisms by which these polymorphisms can result in severe malaria protection and investigate the implications of these associations for wider health. Funding Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative.
- Published
- 2018
23. Evaluation of the diagnostic accuracy and cost of different methods for the assessment of severe anaemia in hospitalised children in Eastern Uganda
- Author
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Olupot-Olupot, Peter, primary, Prevatt, Natalie, additional, Engoru, Charles, additional, Nteziyaremye, Julius, additional, Amorut, Denis, additional, Chebet, Martin, additional, Senyondo, Tonny, additional, Ongodia, Paul, additional, Ndila, Carolyne M., additional, Williams, Thomas N., additional, and Maitland, Kathryn, additional
- Published
- 2019
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24. Evaluation of the diagnostic accuracy and cost of different methods for the assessment of severe anaemia in hospitalised children in Eastern Uganda
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Olupot-Olupot, Peter, primary, Prevatt, Natalie, additional, Engoru, Charles, additional, Nteziyaremye, Julius, additional, Amorut, Denis, additional, Chebet, Martin, additional, Senyondo, Tonny, additional, Ongodia, Paul, additional, Ndila, Carolyne M., additional, Williams, Thomas N., additional, and Maitland, Kathryn, additional
- Published
- 2018
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25. Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia
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Opi, D Herbert, primary, Swann, Olivia, additional, Macharia, Alexander, additional, Uyoga, Sophie, additional, Band, Gavin, additional, Ndila, Carolyne M, additional, Harrison, Ewen M, additional, Thera, Mahamadou A, additional, Kone, Abdoulaye K, additional, Diallo, Dapa A, additional, Doumbo, Ogobara K, additional, Lyke, Kirsten E, additional, Plowe, Christopher V, additional, Moulds, Joann M, additional, Shebbe, Mohammed, additional, Mturi, Neema, additional, Peshu, Norbert, additional, Maitland, Kathryn, additional, Raza, Ahmed, additional, Kwiatkowski, Dominic P, additional, Rockett, Kirk A, additional, Williams, Thomas N, additional, and Rowe, J Alexandra, additional
- Published
- 2018
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- View/download PDF
26. Author response: Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia
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Opi, D Herbert, primary, Swann, Olivia, additional, Macharia, Alexander, additional, Uyoga, Sophie, additional, Band, Gavin, additional, Ndila, Carolyne M, additional, Harrison, Ewen M, additional, Thera, Mahamadou A, additional, Kone, Abdoulaye K, additional, Diallo, Dapa A, additional, Doumbo, Ogobara K, additional, Lyke, Kirsten E, additional, Plowe, Christopher V, additional, Moulds, Joann M, additional, Shebbe, Mohammed, additional, Mturi, Neema, additional, Peshu, Norbert, additional, Maitland, Kathryn, additional, Raza, Ahmed, additional, Kwiatkowski, Dominic P, additional, Rockett, Kirk A, additional, Williams, Thomas N, additional, and Rowe, J Alexandra, additional
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- 2018
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27. The clinical epidemiology of sickle cell anemia In Africa
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Macharia, Alex W., primary, Mochamah, George, additional, Uyoga, Sophie, additional, Ndila, Carolyne M., additional, Nyutu, Gideon, additional, Makale, Johnstone, additional, Tendwa, Metrine, additional, Nyatichi, Emily, additional, Ojal, John, additional, Shebe, Mohammed, additional, Awuondo, Kennedy O., additional, Mturi, Neema, additional, Peshu, Norbert, additional, Tsofa, Benjamin, additional, Scott, J. Anthony G., additional, Maitland, Kathryn, additional, and Williams, Thomas N., additional
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- 2017
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28. A novel locus of resistance to severe malaria in a region of ancient balancing selection
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Band, Gavin, Rockett, Kirk A., Spencer, Chris C. A., Kwiatkowski, Dominic P., Si Le, Quang, Clarke, Geraldine M., Kivinen, Katja, Leffler, Ellen M., Cornelius, Victoria, Conway, David J., Williams, Thomas N., Taylor, Terrie, Bojang, Kalifa A., Doumbo, Ogobara, Thera, Mahamadou A., Modiano, David, Sirima, Sodiomon B., Wilson, Michael D, Koram, Kwadwo A., Agbenyega, Tsiri, Achidi, Eric, Marsh, Kevin, Reyburn, Hugh, Drakeley, Chris, Riley, Eleanor, Molyneux, Malcolm, Jallow, Muminatou, Pinder, Margaret, Toure, Ousmane B., Konate, Salimata, Sissoko, Sibiri, Bougouma, Edith C., Mangano, Valentina D., Amenga Etego, Lucas N., Ghansah, Anita K., Hodgson, Abraham V. O., Wilson, Michael D., Ansong, Daniel, Enimil, Anthony, Evans, Jennifer, Apinjoh, Tobias O., Macharia, Alexander, Ndila, Carolyne M., Newton, Charles, Peshu, Norbert, Uyoga, Sophie, Manjurano, Alphaxard, Kachala, David, Nyirongo, Vysaul, Mead, Daniel, Drury, Eleanor, Auburn, Sarah, Campino, Susana G., Macinnis, Bronwyn, Stalker, Jim, Gray, Emma, Hubbart, Christina, Jeffreys, Anna E., Rowlands, Kate, Mendy, Alieu, Craik, Rachel, Fitzpatrick, Kathryn, Molloy, Sile, Hart, Lee, Hutton, Robert, Kerasidou, Angeliki, and Johnson, Kimberly J.
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Male ,Erythrocytes ,Genome-wide association study ,Balancing selection ,0302 clinical medicine ,Glycophorins ,Malaria, Falciparum ,malaria ,genetic ,resistance ,Child ,Conserved Sequence ,Genetics ,0303 health sciences ,Extracellular Matrix Proteins ,Multidisciplinary ,Natural selection ,Single Nucleotide ,3. Good health ,Female ,Glycophorin ,Falciparum ,Pan troglodytes ,Evolution ,Plasmodium falciparum ,Locus (genetics) ,Biology ,Polymorphism, Single Nucleotide ,Article ,ABO Blood-Group System ,Host-Parasite Interactions ,Evolution, Molecular ,03 medical and health sciences ,Genetic ,parasitic diseases ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Polymorphism ,Selection, Genetic ,Selection ,Gene ,030304 developmental biology ,Haplotype ,Erythrocyte Membrane ,Molecular ,medicine.disease ,biology.organism_classification ,Malaria ,Haplotypes ,Africa ,Genome-Wide Association Study ,030217 neurology & neurosurgery - Abstract
Malaria Genomic Epidemiology Network The high prevalence of sickle haemoglobin in Africa shows that malaria has been a major force for human evolutionary selection, but surprisingly few other polymorphisms have been proven to confer resistance to malaria in large epidemiological studies. To address this problem, we conducted a multi-centre genome-wide association study (GWAS) of life-threatening Plasmodium falciparum infection (severe malaria) in over 11,000 African children, with replication data in a further 14,000 individuals. Here we report a novel malaria resistance locus close to a cluster of genes encoding glycophorins that are receptors for erythrocyte invasion by P. falciparum. We identify a haplotype at this locus that provides 33% protection against severe malaria (odds ratio= 0.67, 95% confidence interval= 0.60-0.76, P value= 9.5× 10-11) and is linked to polymorphisms that have previously been shown to have features of ancient balancing selection, on the basis of haplotype sharing between humans and chimpanzees. Taken together with previous observations on the malaria-protective role of blood group O, these data reveal that two of the strongest GWAS signals for severe malaria lie in or close to genes encoding the glycosylated surface coat of the erythrocyte cell membrane, both within regions of the genome where it appears that evolution has maintained diversity for millions of years. These findings provide new insights into the host-parasite interactions that are critical in determining the outcome of malaria infection.
- Published
- 2014
29. Admixture into and within sub-Saharan Africa.
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Busby, George B. J., Band, Gavin, Quang Si Le, Jallow, Muminatou, Bougama, Edith, Mangano, Valentina D., Amenga-Etego, Lucas N., Enimil, Anthony, Apinjoh, Tobias, Ndila, Carolyne M., Manjurano, Alphaxard, Nyirongo, Vysaul, Doumba, Ogobara, Rockett, Kirk A., Kwiatkowski, Dominic P., Spencer, Chris C. A., and Network, Malaria Genomic Epidemiology
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- 2016
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30. Resistance to malaria through structural variation of red blood cell invasion receptors.
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Leffler, Ellen M., Band, Gavin, Busby, George B. J., Kivinen, Katja, Si Le, Quang, Clarke, Geraldine M., Bojang, Kalifa A., Conway, David J., Jallow, Muminatou, Sisay-Joof, Fatoumatta, Bougouma, Edith C., Mangano, Valentina D., Modiano, David, Sirima, Sodiomon B., Achidi, Eric, Apinjoh, Tobias O., Marsh, Kevin, Ndila, Carolyne M., Peshu, Norbert, and Williams, Thomas N.
- Published
- 2017
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31. Haplotype heterogeneity and low linkage disequilibrium reduce reliable prediction of genotypes for the ‑α 3.7I form of α-thalassaemia using genome-wide microarray data.
- Author
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Ndila CM, Nyirongo V, Macharia AW, Jeffreys AE, Rowlands K, Hubbart C, Busby GBJ, Band G, Harding RM, Rockett KA, and Williams TN
- Abstract
Background: The -α
3.7I -thalassaemia deletion is very common throughout Africa because it protects against malaria. When undertaking studies to investigate human genetic adaptations to malaria or other diseases, it is important to account for any confounding effects of α-thalassaemia to rule out spurious associations. Methods: In this study, we have used direct α-thalassaemia genotyping to understand why GWAS data from a large malaria association study in Kilifi Kenya did not identify the α-thalassaemia signal. We then explored the potential use of a number of new approaches to using GWAS data for imputing α-thalassaemia as an alternative to direct genotyping by PCR. Results: We found very low linkage-disequilibrium of the directly typed data with the GWAS SNP markers around α-thalassaemia and across the haemoglobin-alpha ( HBA ) gene region, which along with a complex haplotype structure, could explain the lack of an association signal from the GWAS SNP data. Some indirect typing methods gave results that were in broad agreement with those derived from direct genotyping and could identify an association signal, but none were sufficiently accurate to allow correct interpretation compared with direct typing, leading to confusing or erroneous results. Conclusions: We conclude that going forwards, direct typing methods such as PCR will still be required to account for α-thalassaemia in GWAS studies., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Ndila CM et al.)- Published
- 2021
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32. Haplotype heterogeneity and low linkage disequilibrium reduce reliable prediction of genotypes for the ‑α 3.7I form of α-thalassaemia using genome-wide microarray data.
- Author
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Ndila CM, Nyirongo V, Macharia AW, Jeffreys AE, Rowlands K, Hubbart C, Busby GBJ, Band G, Harding RM, Rockett KA, and Williams TN
- Abstract
Background: The -α
3.7I -thalassaemia deletion is very common throughout Africa because it protects against malaria. When undertaking studies to investigate human genetic adaptations to malaria or other diseases, it is important to account for any confounding effects of α-thalassaemia to rule out spurious associations. Methods: In this study we have used direct α-thalassaemia genotyping to understand why GWAS data from a large malaria association study in Kilifi Kenya did not identify the α-thalassaemia signal. We then explored the potential use of a number of new approaches to using GWAS data for imputing α-thalassaemia as an alternative to direct genotyping by PCR. Results: We found very low linkage-disequilibrium of the directly typed data with the GWAS SNP markers around α-thalassaemia and across the haemoglobin-alpha ( HBA ) gene region, which along with a complex haplotype structure, could explain the lack of an association signal from the GWAS SNP data. Some indirect typing methods gave results that were in broad agreement with those derived from direct genotyping and could identify an association signal, but none were sufficiently accurate to allow correct interpretation compared with direct typing, leading to confusing or erroneous results. Conclusions: We conclude that going forwards, direct typing methods such as PCR will still be required to account for α-thalassaemia in GWAS studies., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Ndila CM et al.)- Published
- 2020
- Full Text
- View/download PDF
33. Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study.
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Ndila CM, Uyoga S, Macharia AW, Nyutu G, Peshu N, Ojal J, Shebe M, Awuondo KO, Mturi N, Tsofa B, Sepúlveda N, Clark TG, Band G, Clarke G, Rowlands K, Hubbart C, Jeffreys A, Kariuki S, Marsh K, Mackinnon M, Maitland K, Kwiatkowski DP, Rockett KA, and Williams TN
- Subjects
- Case-Control Studies, Child, Child, Preschool, Female, Gene Frequency, Humans, Kenya, Male, Genetic Predisposition to Disease genetics, Malaria genetics, Polymorphism, Genetic
- Abstract
Background: Human genetic factors are important determinants of malaria risk. We investigated associations between multiple candidate polymorphisms-many related to the structure or function of red blood cells-and risk for severe Plasmodium falciparum malaria and its specific phenotypes, including cerebral malaria, severe malaria anaemia, and respiratory distress., Methods: We did a case-control study in Kilifi County, Kenya. We recruited as cases children presenting with severe malaria to the high-dependency ward of Kilifi County Hospital. We included as controls infants born in the local community between Aug 1, 2006, and Sept 30, 2010, who were part of a genetics study. We tested for associations between a range of candidate malaria-protective genes and risk for severe malaria and its specific phenotypes. We used a permutation approach to account for multiple comparisons between polymorphisms and severe malaria. We judged p values less than 0·005 significant for the primary analysis of the association between candidate genes and severe malaria., Findings: Between June 11, 1995, and June 12, 2008, 2244 children with severe malaria were recruited to the study, and 3949 infants were included as controls. Overall, 263 (12%) of 2244 children with severe malaria died in hospital, including 196 (16%) of 1233 with cerebral malaria. We investigated 121 polymorphisms in 70 candidate severe malaria-associated genes. We found significant associations between risk for severe malaria overall and polymorphisms in 15 genes or locations, of which most were related to red blood cells: ABO, ATP2B4, ARL14, CD40LG, FREM3, INPP4B, G6PD, HBA (both HBA1 and HBA2), HBB, IL10, LPHN2 (also known as ADGRL2), LOC727982, RPS6KL1, CAND1, and GNAS. Combined, these genetic associations accounted for 5·2% of the variance in risk for developing severe malaria among individuals in the general population. We confirmed established associations between severe malaria and sickle-cell trait (odds ratio [OR] 0·15, 95% CI 0·11-0·20; p=2·61 × 10
-58 ), blood group O (0·74, 0·66-0·82; p=6·26 × 10-8 ), and -α3·7 -thalassaemia (0·83, 0·76-0·90; p=2·06 × 10-6 ). We also found strong associations between overall risk of severe malaria and polymorphisms in both ATP2B4 (OR 0·76, 95% CI 0·63-0·92; p=0·001) and FREM3 (0·64, 0·53-0·79; p=3·18 × 10-14 ). The association with FREM3 could be accounted for by linkage disequilibrium with a complex structural mutation within the glycophorin gene region (comprising GYPA, GYPB, and GYPE) that encodes for the rare Dantu blood group antigen. Heterozygosity for Dantu was associated with risk for severe malaria (OR 0·57, 95% CI 0·49-0·68; p=3·22 × 10-11 ), as was homozygosity (0·26, 0·11-0·62; p=0·002)., Interpretation: Both ATP2B4 and the Dantu blood group antigen are associated with the structure and function of red blood cells. ATP2B4 codes for plasma membrane calcium-transporting ATPase 4 (the major calcium pump on red blood cells) and the glycophorins are ligands for parasites to invade red blood cells. Future work should aim at uncovering the mechanisms by which these polymorphisms can result in severe malaria protection and investigate the implications of these associations for wider health., Funding: Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
34. Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.
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Clarke GM, Rockett K, Kivinen K, Hubbart C, Jeffreys AE, Rowlands K, Jallow M, Conway DJ, Bojang KA, Pinder M, Usen S, Sisay-Joof F, Sirugo G, Toure O, Thera MA, Konate S, Sissoko S, Niangaly A, Poudiougou B, Mangano VD, Bougouma EC, Sirima SB, Modiano D, Amenga-Etego LN, Ghansah A, Koram KA, Wilson MD, Enimil A, Evans J, Amodu OK, Olaniyan S, Apinjoh T, Mugri R, Ndi A, Ndila CM, Uyoga S, Macharia A, Peshu N, Williams TN, Manjurano A, Sepúlveda N, Clark TG, Riley E, Drakeley C, Reyburn H, Nyirongo V, Kachala D, Molyneux M, Dunstan SJ, Phu NH, Quyen NN, Thai CQ, Hien TT, Manning L, Laman M, Siba P, Karunajeewa H, Allen S, Allen A, Davis TM, Michon P, Mueller I, Molloy SF, Campino S, Kerasidou A, Cornelius VJ, Hart L, Shah SS, Band G, Spencer CC, Agbenyega T, Achidi E, Doumbo OK, Farrar J, Marsh K, Taylor T, and Kwiatkowski DP
- Subjects
- Alleles, Anemia pathology, Case-Control Studies, Glucosephosphate Dehydrogenase genetics, Humans, Malaria, Cerebral pathology, Malaria, Falciparum pathology, Risk Assessment, Anemia epidemiology, Glucosephosphate Dehydrogenase Deficiency complications, Malaria, Cerebral epidemiology, Malaria, Falciparum epidemiology
- Abstract
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations., Competing Interests: JF: Director of the Wellcome Trust, one of the three founding funders of eLife. The other authors declare that no competing interests exist.
- Published
- 2017
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