Search

Your search keyword '"Jallow M"' showing total 7 results
Start Over Author "Jallow M" Publisher nature publishing group
7 results on '"Jallow M"'

1. Reappraisal of known malaria resistance loci in a large multicenter study

Author

Rockett, KA, Clarke, GM, Fitzpatrick, K, Hubbart, C, Jeffreys, AE, Rowlands, K, Craik, R, 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, O, Olaniyan, S, Apinjoh, T, Mugri, R, Ndi, A, Ndila, CM, Uyoga, S, Macharia, A, Peshu, N, Williams, TN, Manjurano, A, Riley, E, Drakeley, C, Reyburn, H, Nyirongo, V, Kachala, D, Molyneux, M, Dunstan, SJ, Nguyen, HP, Nguyen, TNQ, Cao, QT, Tran, TH, Manning, L, Laman, M, Siba, P, Karunajeewa, H, Allen, S, Allen, A, Davis, TME, Michon, P, Mueller, I, Green, A, Molloy, S, Johnson, KJ, Kerasidou, A, Cornelius, V, Hart, L, Vanderwal, A, SanJoaquin, M, Band, G, Le, SQ, Pirinen, M, Sepulveda, N, Spencer, CCA, Clark, TG, Agbenyega, T, Achidi, E, Doumbo, O, Farrar, J, Marsh, K, Taylor, T, Kwiatkowski, DP, Rockett, KA, Clarke, GM, Fitzpatrick, K, Hubbart, C, Jeffreys, AE, Rowlands, K, Craik, R, 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, O, Olaniyan, S, Apinjoh, T, Mugri, R, Ndi, A, Ndila, CM, Uyoga, S, Macharia, A, Peshu, N, Williams, TN, Manjurano, A, Riley, E, Drakeley, C, Reyburn, H, Nyirongo, V, Kachala, D, Molyneux, M, Dunstan, SJ, Nguyen, HP, Nguyen, TNQ, Cao, QT, Tran, TH, Manning, L, Laman, M, Siba, P, Karunajeewa, H, Allen, S, Allen, A, Davis, TME, Michon, P, Mueller, I, Green, A, Molloy, S, Johnson, KJ, Kerasidou, A, Cornelius, V, Hart, L, Vanderwal, A, SanJoaquin, M, Band, G, Le, SQ, Pirinen, M, Sepulveda, N, Spencer, CCA, Clark, TG, Agbenyega, T, Achidi, E, Doumbo, O, Farrar, J, Marsh, K, Taylor, T, and Kwiatkowski, DP

Abstract

Many human genetic associations with resistance to malaria have been reported, but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. We tested 55 SNPs in 27 loci previously reported to associate with severe malaria. There was evidence of association at P < 1 × 10(-4) with the HBB, ABO, ATP2B4, G6PD and CD40LG loci, but previously reported associations at 22 other loci did not replicate in the multicenter analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, with a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed.

Published
2014

2. Genome-wide association study identifies eight loci associated with blood pressure

Author

Newton-Cheh, C, Johnson, T, Gateva, V, Tobin, MD, Bochud, M, Coin, L, Najjar, SS, Zhao, JH, Heath, SC, Eyheramendy, S, Papadakis, K, Voight, BF, Scott, LJ, Zhang, F, Farrall, M, Tanaka, T, Wallace, C, Chambers, JC, Khaw, K, Nilsson, P, Van Der Harst, P, Polidoro, S, Grobbee, DE, Onland-Moret, NC, Bots, ML, Wain, LV, Elliot, KS, Teumer, A, Luan, J, Lucas, G, Kuusisto, J, Burton, PR, Hadley, D, McArdle, WL, Brown, M, Dominiczak, A, Newhouse, SJ, Samani, NJ, Webster, J, Zeggini, E, Beckmann, JS, Bergmann, S, Lim, N, Song, K, Vollenweider, P, Waeber, G, Waterworth, DM, Yuan, X, Groop, L, Orho-Melander, M, Allione, A, Di Gregorio, A, Guarrera, S, Panico, S, Ricceri, F, Romanazzi, V, Sacerdote, C, Vineis, P, Barroso, I, Sandhu, MS, Luben, RN, Crawford, GJ, Jousilahti, P, Perola, M, Boehnke, M, Bonnycastle, LL, Collins, FS, Jackson, AU, Mohlke, KL, Stringham, HM, Valle, TT, Willer, CJ, Bergman, RN, Morken, MA, Döring, A, Gieger, C, Illig, T, Meitinger, T, Org, E, Pfeufer, A, Wichmann, HE, Kathiresan, S, Marrugat, J, O'Donnell, CJ, Schwartz, SM, Siscovick, DS, Subirana, I, Freimer, NB, Hartikainen, A, McCarthy, MI, O'Reilly, PF, Peltonen, L, Pouta, A, De Jong, PE, Snieder, H, Van Gilst, WH, Clarke, R, Goel, A, Hamsten, A, Altshuler, D, Jarvelin, M, Elliott, P, Lakatta, EG, Forouhi, N, Wareham, NJ, Loos, RJF, Deloukas, P, Lathrop, GM, Zelenika, D, Strachan, DP, Soranzo, N, Williams, FM, Zhai, G, Spector, TD, Peden, JF, Watkins, H, Ferrucci, L, Caulfield, M, Munroe, PB, Berglund, G, Melander, O, Matullo, G, Uiterwaal, CS, van der Schouw, YT, Numans, ME, Ernst, F, Homuth, G, Völker, U, Elosua, R, Laakso, M, Connell, JM, Mooser, V, Salomaa, V, Tuomilehto, J, Laan, M, Navis, G, Seedorf, U, Syvänen, A, Tognoni, G, Sanna, S, Uda, M, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Felix, SB, Reffelmann, T, Lorbeer, R, Völzke, H, Rettig, R, Galan, P, Hercberg, S, Bingham, SA, Kooner, JS, Bandinelli, S, Meneton, P, Abecasis, G, Thompson, JR, Braga Marcano, CA, Barke, B, Dobson, R, Gungadoo, J, Lee, KL, Onipinla, A, Wallace, I, Xue, M, Clayton, DG, Leung, H, Nutland, S, Walker, NM, Todd, JA, Stevens, HE, Dunger, DB, Widmer, B, Downes, K, Cardon, LR, Kwiatkowski, DP, Barrett, JC, Evans, D, Morris, AP, Lindgren, CM, Rayner, NW, Timpson, NJ, Lyons, E, Vannberg, F, Hill, AVS, Teo, YY, Rockett, KA, Craddock, N, Attwood, AP, Bryan, C, Bumpstead, SJ, Chaney, A, Ghori, J, William, RG, Hunt, SE, Inouye, M, Keniry, E, King, E, McGinnis, R, Potter, S, Ravindrarajan, R, Whittaker, P, Withers, D, Bentley, D, Groves, CJ, Duncanson, A, Ouwehand, WH, Boorman, JP, Cant, B, Jolley, JD, Knight, AS, Koch, K, Taylor, NC, Watkins, NA, Winzer, T, Braund, PS, Dixon, RJ, Mangino, M, Stevens, S, Donnely, P, Davidson, D, Marchini, JL, Spencer, ICA, Cardin, NJ, Ferreira, T, Pereira-Gale, J, Hallgrimsdottir, IB, Howie, BN, Su, Z, Vukcevic, D, Easton, D, Everson, U, Hussey, JM, Meech, E, Prowse, CV, Walters, GR, Jones, RW, Ring, SM, Prembey, M, Breen, G, St Clair, D, Ceasar, S, Gordon-Smith, K, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Holmans, PA, Jones, IR, Kirov, G, Moskovina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Farmer, A, Williamson, R, McGruffin, P, Young, AH, Ferrier, IN, Ball, SG, Balmforth, AJ, Barrett, JH, Bishop, DT, Iles, MM, Maqbool, A, Yuldasheva, N, Hall, AS, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, CW, Nimmo, ER, Satsangi, J, Fisher, SA, Lewis, CM, Onnie, CM, Prescott, NJ, Mathew, CG, Forbes, A, Sanderson, J, Mathew, C, Barbour, J, Mohiuddin, MK, Todhunter, CE, Mansfield, JC, Ahmad, T, Cummings, FR, Jewell, DP, Barton, A, Bruce, IN, Donovan, H, Eyre, S, Gilbert, PD, Hider, SL, Hinks, AM, John, SL, Potter, C, Silman, AJ, Symmons, DPM, Thomson, W, Worthington, J, Frayling, TM, Freathy, RM, Lango, H, Perry, JRB, Weedon, MN, Hattersley, AT, Shields, BM, Hitman, GA, Walker, M, Newport, M, Sirugo, G, Conway, D, Jallow, M, Bradbury, LA, Pointon, JL, Brown, MA, Farrar, C, Wordsworth, P, Franklyn, JA, Heward, JM, Simmonds, MJ, Cough, SCL, Seal, S, Stratton, MR, Ban, M, Goris, A, Sawcer, SJ, Compston, A, Newton-Cheh, C, Johnson, T, Gateva, V, Tobin, MD, Bochud, M, Coin, L, Najjar, SS, Zhao, JH, Heath, SC, Eyheramendy, S, Papadakis, K, Voight, BF, Scott, LJ, Zhang, F, Farrall, M, Tanaka, T, Wallace, C, Chambers, JC, Khaw, K, Nilsson, P, Van Der Harst, P, Polidoro, S, Grobbee, DE, Onland-Moret, NC, Bots, ML, Wain, LV, Elliot, KS, Teumer, A, Luan, J, Lucas, G, Kuusisto, J, Burton, PR, Hadley, D, McArdle, WL, Brown, M, Dominiczak, A, Newhouse, SJ, Samani, NJ, Webster, J, Zeggini, E, Beckmann, JS, Bergmann, S, Lim, N, Song, K, Vollenweider, P, Waeber, G, Waterworth, DM, Yuan, X, Groop, L, Orho-Melander, M, Allione, A, Di Gregorio, A, Guarrera, S, Panico, S, Ricceri, F, Romanazzi, V, Sacerdote, C, Vineis, P, Barroso, I, Sandhu, MS, Luben, RN, Crawford, GJ, Jousilahti, P, Perola, M, Boehnke, M, Bonnycastle, LL, Collins, FS, Jackson, AU, Mohlke, KL, Stringham, HM, Valle, TT, Willer, CJ, Bergman, RN, Morken, MA, Döring, A, Gieger, C, Illig, T, Meitinger, T, Org, E, Pfeufer, A, Wichmann, HE, Kathiresan, S, Marrugat, J, O'Donnell, CJ, Schwartz, SM, Siscovick, DS, Subirana, I, Freimer, NB, Hartikainen, A, McCarthy, MI, O'Reilly, PF, Peltonen, L, Pouta, A, De Jong, PE, Snieder, H, Van Gilst, WH, Clarke, R, Goel, A, Hamsten, A, Altshuler, D, Jarvelin, M, Elliott, P, Lakatta, EG, Forouhi, N, Wareham, NJ, Loos, RJF, Deloukas, P, Lathrop, GM, Zelenika, D, Strachan, DP, Soranzo, N, Williams, FM, Zhai, G, Spector, TD, Peden, JF, Watkins, H, Ferrucci, L, Caulfield, M, Munroe, PB, Berglund, G, Melander, O, Matullo, G, Uiterwaal, CS, van der Schouw, YT, Numans, ME, Ernst, F, Homuth, G, Völker, U, Elosua, R, Laakso, M, Connell, JM, Mooser, V, Salomaa, V, Tuomilehto, J, Laan, M, Navis, G, Seedorf, U, Syvänen, A, Tognoni, G, Sanna, S, Uda, M, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Felix, SB, Reffelmann, T, Lorbeer, R, Völzke, H, Rettig, R, Galan, P, Hercberg, S, Bingham, SA, Kooner, JS, Bandinelli, S, Meneton, P, Abecasis, G, Thompson, JR, Braga Marcano, CA, Barke, B, Dobson, R, Gungadoo, J, Lee, KL, Onipinla, A, Wallace, I, Xue, M, Clayton, DG, Leung, H, Nutland, S, Walker, NM, Todd, JA, Stevens, HE, Dunger, DB, Widmer, B, Downes, K, Cardon, LR, Kwiatkowski, DP, Barrett, JC, Evans, D, Morris, AP, Lindgren, CM, Rayner, NW, Timpson, NJ, Lyons, E, Vannberg, F, Hill, AVS, Teo, YY, Rockett, KA, Craddock, N, Attwood, AP, Bryan, C, Bumpstead, SJ, Chaney, A, Ghori, J, William, RG, Hunt, SE, Inouye, M, Keniry, E, King, E, McGinnis, R, Potter, S, Ravindrarajan, R, Whittaker, P, Withers, D, Bentley, D, Groves, CJ, Duncanson, A, Ouwehand, WH, Boorman, JP, Cant, B, Jolley, JD, Knight, AS, Koch, K, Taylor, NC, Watkins, NA, Winzer, T, Braund, PS, Dixon, RJ, Mangino, M, Stevens, S, Donnely, P, Davidson, D, Marchini, JL, Spencer, ICA, Cardin, NJ, Ferreira, T, Pereira-Gale, J, Hallgrimsdottir, IB, Howie, BN, Su, Z, Vukcevic, D, Easton, D, Everson, U, Hussey, JM, Meech, E, Prowse, CV, Walters, GR, Jones, RW, Ring, SM, Prembey, M, Breen, G, St Clair, D, Ceasar, S, Gordon-Smith, K, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Holmans, PA, Jones, IR, Kirov, G, Moskovina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Farmer, A, Williamson, R, McGruffin, P, Young, AH, Ferrier, IN, Ball, SG, Balmforth, AJ, Barrett, JH, Bishop, DT, Iles, MM, Maqbool, A, Yuldasheva, N, Hall, AS, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, CW, Nimmo, ER, Satsangi, J, Fisher, SA, Lewis, CM, Onnie, CM, Prescott, NJ, Mathew, CG, Forbes, A, Sanderson, J, Mathew, C, Barbour, J, Mohiuddin, MK, Todhunter, CE, Mansfield, JC, Ahmad, T, Cummings, FR, Jewell, DP, Barton, A, Bruce, IN, Donovan, H, Eyre, S, Gilbert, PD, Hider, SL, Hinks, AM, John, SL, Potter, C, Silman, AJ, Symmons, DPM, Thomson, W, Worthington, J, Frayling, TM, Freathy, RM, Lango, H, Perry, JRB, Weedon, MN, Hattersley, AT, Shields, BM, Hitman, GA, Walker, M, Newport, M, Sirugo, G, Conway, D, Jallow, M, Bradbury, LA, Pointon, JL, Brown, MA, Farrar, C, Wordsworth, P, Franklyn, JA, Heward, JM, Simmonds, MJ, Cough, SCL, Seal, S, Stratton, MR, Ban, M, Goris, A, Sawcer, SJ, and Compston, A

Abstract

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10−24), CYP1A2 (P = 1 × 10−23), FGF5 (P = 1 × 10−21), SH2B3 (P = 3 × 10−18), MTHFR (P = 2 × 10−13), c10orf107 (P = 1 × 10−9), ZNF652 (P = 5 × 10−9) and PLCD3 (P = 1 × 10−8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

3. Malaria protection due to sickle haemoglobin depends on parasite genotype.

Author

Band G, Leffler EM, Jallow M, Sisay-Joof F, Ndila CM, Macharia AW, Hubbart C, Jeffreys AE, Rowlands K, Nguyen T, Gonçalves S, Ariani CV, Stalker J, Pearson RD, Amato R, Drury E, Sirugo G, d'Alessandro U, Bojang KA, Marsh K, Peshu N, Saelens JW, Diakité M, Taylor SM, Conway DJ, Williams TN, Rockett KA, and Kwiatkowski DP

Subjects
Alleles, Animals, Child, Female, Gambia epidemiology, Genes, Protozoan genetics, Humans, Kenya epidemiology, Linkage Disequilibrium, Malaria, Falciparum epidemiology, Male, Polymorphism, Genetic, Genotype, Hemoglobin, Sickle genetics, Host Adaptation genetics, Malaria, Falciparum blood, Malaria, Falciparum parasitology, Parasites genetics, Plasmodium falciparum genetics
Abstract

Host genetic factors can confer resistance against malaria 1 , raising the question of whether this has led to evolutionary adaptation of parasite populations. Here we searched for association between candidate host and parasite genetic variants in 3,346 Gambian and Kenyan children with severe malaria caused by Plasmodium falciparum. We identified a strong association between sickle haemoglobin (HbS) in the host and three regions of the parasite genome, which is not explained by population structure or other covariates, and which is replicated in additional samples. The HbS-associated alleles include nonsynonymous variants in the gene for the acyl-CoA synthetase family member 2-4 PfACS8 on chromosome 2, in a second region of chromosome 2, and in a region containing structural variation on chromosome 11. The alleles are in strong linkage disequilibrium and have frequencies that covary with the frequency of HbS across populations, in particular being much more common in Africa than other parts of the world. The estimated protective effect of HbS against severe malaria, as determined by comparison of cases with population controls, varies greatly according to the parasite genotype at these three loci. These findings open up a new avenue of enquiry into the biological and epidemiological significance of the HbS-associated polymorphisms in the parasite genome and the evolutionary forces that have led to their high frequency and strong linkage disequilibrium in African P. falciparum populations., (© 2021. The Author(s).)

Published
2022
Full Text
View/download PDF

4. Precision identification of high-risk phenotypes and progression pathways in severe malaria without requiring longitudinal data.

Author

Johnston IG, Hoffmann T, Greenbury SF, Cominetti O, Jallow M, Kwiatkowski D, Barahona M, Jones NS, and Casals-Pascual C

Abstract

More than 400,000 deaths from severe malaria (SM) are reported every year, mainly in African children. The diversity of clinical presentations associated with SM indicates important differences in disease pathogenesis that require specific treatment, and this clinical heterogeneity of SM remains poorly understood. Here, we apply tools from machine learning and model-based inference to harness large-scale data and dissect the heterogeneity in patterns of clinical features associated with SM in 2904 Gambian children admitted to hospital with malaria. This quantitative analysis reveals features predicting the severity of individual patient outcomes, and the dynamic pathways of SM progression, notably inferred without requiring longitudinal observations. Bayesian inference of these pathways allows us assign quantitative mortality risks to individual patients. By independently surveying expert practitioners, we show that this data-driven approach agrees with and expands the current state of knowledge on malaria progression, while simultaneously providing a data-supported framework for predicting clinical risk., Competing Interests: Competing interestsThe authors declare no competing interests.

Published
2019
Full Text
View/download PDF

5. Identification of a Novel Clinical Phenotype of Severe Malaria using a Network-Based Clustering Approach.

Author

Cominetti O, Smith D, Hoffman F, Jallow M, Thézénas ML, Huang H, Kwiatkowski D, Maini PK, and Casals-Pascual C

Subjects
Anemia etiology, Biomarkers, Child, Child, Preschool, Female, Humans, Malaria complications, Malaria mortality, Malaria, Falciparum diagnosis, Malaria, Falciparum mortality, Malaria, Falciparum parasitology, Male, Plasmodium falciparum, Severity of Illness Index, Malaria diagnosis, Malaria parasitology, Neural Networks, Computer, Phenotype
Abstract

The parasite Plasmodium falciparum is the main cause of severe malaria (SM). Despite treatment with antimalarial drugs, more than 400,000 deaths are reported every year, mainly in African children. The diversity of clinical presentations associated with SM highlights important differences in disease pathogenesis that often require specific therapeutic options. The clinical heterogeneity of SM is largely unresolved. Here we report a network-based analysis of clinical phenotypes associated with SM in 2,915 Gambian children admitted to hospital with Plasmodium falciparum malaria. We used a network-based clustering method which revealed a strong correlation between disease heterogeneity and mortality. The analysis identified four distinct clusters of SM and respiratory distress that departed from the WHO definition. Patients in these clusters characteristically presented with liver enlargement and high concentrations of brain natriuretic peptide (BNP), giving support to the potential role of circulatory overload and/or right-sided heart failure as a mechanism of disease. The role of heart failure is controversial in SM and our work suggests that standard clinical management may not be appropriate. We find that our clustering can be a powerful data exploration tool to identify novel disease phenotypes and therapeutic options to reduce malaria-associated mortality.

Published
2018
Full Text
View/download PDF

6. The African Genome Variation Project shapes medical genetics in Africa.

Author

Gurdasani D, Carstensen T, Tekola-Ayele F, Pagani L, Tachmazidou I, Hatzikotoulas K, Karthikeyan S, Iles L, Pollard MO, Choudhury A, Ritchie GR, Xue Y, Asimit J, Nsubuga RN, Young EH, Pomilla C, Kivinen K, Rockett K, Kamali A, Doumatey AP, Asiki G, Seeley J, Sisay-Joof F, Jallow M, Tollman S, Mekonnen E, Ekong R, Oljira T, Bradman N, Bojang K, Ramsay M, Adeyemo A, Bekele E, Motala A, Norris SA, Pirie F, Kaleebu P, Kwiatkowski D, Tyler-Smith C, Rotimi C, Zeggini E, and Sandhu MS

Subjects
Africa, Africa South of the Sahara, Asia ethnology, Europe ethnology, Humans, Risk Factors, Selection, Genetic genetics, Genetic Variation genetics, Genetics, Medical trends, Genome, Human genetics, Genomics trends
Abstract

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.

Published
2015
Full Text
View/download PDF

7. Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibility.

Author

Clark TG, Fry AE, Auburn S, Campino S, Diakite M, Green A, Richardson A, Teo YY, Small K, Wilson J, Jallow M, Sisay-Joof F, Pinder M, Sabeti P, Kwiatkowski DP, and Rockett KA

Subjects
Africa, Western, Animals, Case-Control Studies, Female, Gene Frequency, Genetic Linkage, Genetic Predisposition to Disease, Glucosephosphate Dehydrogenase genetics, Glycogen Storage Disease Type I complications, Humans, Malaria, Falciparum complications, Male, Plasmodium falciparum, Polymorphism, Single Nucleotide, Severity of Illness Index, Genetic Heterogeneity, Glycogen Storage Disease Type I genetics, Malaria, Falciparum genetics
Abstract

Several lines of evidence link glucose-6-phosphate dehydrogenase (G6PD) deficiency to protection from severe malaria. Early reports suggested most G6PD deficiency in sub-Saharan Africa was because of the 202A/376G G6PD A- allele, and recent association studies of G6PD deficiency have employed genotyping as a convenient way to determine enzyme status. However, further work has suggested that other G6PD deficiency alleles are relatively common in some regions of West Africa. To investigate the consequences of unrecognized allelic heterogeneity on association studies, in particular studies of G6PD deficiency and malaria, we carried out a case-control analysis of 2488 Gambian children with severe malaria and 3875 controls. No significant association was found between severe malaria and the 202A/376G G6PD A- allele when analyzed alone, but pooling 202A/376G with other deficiency alleles revealed the signal of protection (male odds ratio (OR) 0.77, 95% CI 0.62-0.95, P=0.016; female OR 0.71, 95% CI 0.56-0.89, P=0.004). We have identified the 968C mutation as the most common G6PD A- allele in The Gambia. Our results highlight some of the consequences of allelic heterogeneity, particularly the increased type I error. They also suggest that G6PD-deficient male hemizygotes and female heterozygotes are protected from severe malaria.

Published
2009
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results