EGAGenomicsMultiomicsN/Ahttps://ega-archive.org/datasets/EGAD000000000180EGA dataset EGAD00000000018EGAWe report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 × 10(-7) to P = 4 × 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.Genome-wide and fine-resolution association analysis of malaria in West Africa.Jallow Muminatou M, Teo Yik Ying YY, Small Kerrin S KS, Rockett Kirk A KA, Deloukas Panos P, Clark Taane G TG, Kivinen Katja K, Bojang Kalifa A KA, Conway David J DJ, Pinder Margaret M, Sirugo Giorgio G, Sisay-Joof Fatou F, Usen Stanley S, Auburn Sarah S, Bumpstead Suzannah J SJ, Campino Susana S, Coffey Alison A, Dunham Andrew A, Fry Andrew E AE, Green Angela A, Gwilliam Rhian R, Hunt Sarah E SE, Inouye Michael M, Jeffreys Anna E AE, Mendy Alieu A, Palotie Aarno A, Potter Simon S, Ragoussis Jiannis J, Rogers Jane J, Rowlands Kate K, Somaskantharajah Elilan E, Whittaker Pamela P, Widden Claire C, Donnelly Peter P, Howie Bryan B, Marchini Jonathan J, Morris Andrew A, SanJoaquin Miguel M, Achidi Eric Akum EA, Agbenyega Tsiri T, Allen Angela A, Amodu Olukemi O, Corran Patrick P, Djimde Abdoulaye A, Dolo Amagana A, Doumbo Ogobara K OK, Drakeley Chris C, Dunstan Sarah S, Evans Jennifer J, Farrar Jeremy J, Fernando Deepika D, Hien Tran Tinh TT, Horstmann Rolf D RD, Ibrahim Muntaser M, Karunaweera Nadira N, Kokwaro Gilbert G, Koram Kwadwo A KA, Lemnge Martha M, Makani Julie J, Marsh Kevin K, Michon Pascal P, Modiano David D, Molyneux Malcolm E ME, Mueller Ivo I, Parker Michael M, Peshu Norbert N, Plowe Christopher V CV, Puijalon Odile O, Reeder John J, Reyburn Hugh H, Riley Eleanor M EM, Sakuntabhai Anavaj A, Singhasivanon Pratap P, Sirima Sodiomon S, Tall Adama A, Taylor Terrie E TE, Thera Mahamadou M, Troye-Blomberg Marita M, Williams Thomas N TN, Wilson Michael M, Kwiatkowski Dominic P DPSMG1, Smg1, rst(1a)cyr, D69, G, 2810024K17Rik, clone 1.24, anon-D69, SMAUG, SmG, CG4555, DmelCG32743, SMGA, Sm-G, CG9742, snRNP-G, CG32743, SAMD4, dSmg1, sm-G, dG, DmelCG9742, SMAUG1, Sm protein G, anon-WO0170980.133, CG5263, snRNPG., SMG, Smg, AL022803, anon-EST:Liang-1.24, smg1, BcDNA:RE61341, HD10913, BcDNA:RH35475, anonD69, DmelCG5263, CG4549Plasmodium Infections, Plasmodium Infection, Infections, Fever, Remittent Fever, Infection, Plasmodium, Remittent, Marsh, plasmodiosis, Severe, Marsh Fever, Paludism, Republic of the Gambia.Plasmodium Infections, wide, wide/broad, Genomes, determination, Plasmodium Infection, Infections, Marsh., Associations, chemical analysis, Fever, Remittent Fever, Infection, Plasmodium, Remittent, assay, whole genome, broad, plasmodiosis, Marsh Fever, PaludismDisequilibrium, Procedures, region or site annotation, Remittent, Progress Reports, broad, supernumerary, Plasmodium Infections, School-Age, Techniques, Investigative, Method, Summary Report, Associations, resistance, Studies, symptoms, Low, attenuated, Summary Reports, Technique, study, School-Age Populations, increased, positional, me75, Progress Report, Genomes, Infections, Linkage Disequilibriums, weak, procedures, Population, SCAN, D17Mit170, T1, Solution, Study, Progress, Linkage, geographical area, Field Reports, Methodological Studies, undulated, Disequilibriums, Republic of the Gambia, Fever, hunchback, African unspecified., School Age Population, Investigative Reports, Marsh, plasmodiosis, Marsh Fever, Paludism, screening, findings, wide/broad, cou, Plasmodium, Procedure, un, Tl3, Tl2, Lr, Investigative Report, School Age, Research Reports, Infection, sequence, techniques, hbs, Populations, positional polypeptide feature, Plasmodium Infection, increased number, Field, signs, whole genome, Methodological, Children, Methodological Study, School Age Populations, wt, primary structure of sequence macromolecule, present in greater numbers in organism, wide, Report, Reports, Remittent Fever, Bra, School-Age Population, Summary, Severe, Field Report, accessory, methodology, Pax-1falseSMGSevere malaria cases from Gambia2018-04-23 10:50:53EGAD00000000018960619465909EGAC00000000002EGAS00000000026