Browsing by Author "Deloukas, P."
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Genome-wide and fine-resolution association analysis of malaria in west Africa(2009-06) Jallow, M.; Teo, Y.Y.; Small, K. S.; Koram, K.A.; Deloukas, P.; Clark, T.G.; Kivinen, K.; Bojang, K.A.; Conway, D.J.; Pinder, M.; Sirugo, G.; Sisay-Joof, F.; Usen, S.; Auburn, S.; Bumpstead, S.J.; Campino, S.; Coffey, A.; Dunham, A.; Fry, A.E.; Green, A.; Gwilliam, R.; Hurt, S.E.; Inouye, M.; Jeffreys, A.E.; Mendy, A.; Palotie, A.; Potter, S.; Ragoussis, J.; Rogers, J.; Rowlands, K.; Somaskantharajah, E.; Whittaker, P.; Wilson, M.; Kwiatkowski, D.P.We 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.Item A global network for investigating the genomic epidemiology of malaria(Nature, 2008-01) Achidi, E.A.; Agbenyega, T.; Allen, S.; Amodu, O.; Bojang, K.; Conway, D.; Corran, P.; Deloukas, P.; Koram, A.K.et.alLarge-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consortial approach that brings together researchers from 21 countries. © 2008 Macmillan Publishers Limited. All rights reserved.Item The Malaria Genomic Epidemiology Network. A global network for investigating the genomic epidemiology of malaria(Nature 456(7223): 732-7, 2008) Achidi, E.A.; Agbenyega, T.; Allen, S.; Amodu, O.; Bojang, K.; Conway, D.; Corran, P.; Deloukas, P.; Djimde, A.; Dolo, A.; Doumbo, O.; Drakeley, C.; Duffy, P.; Dunstan, S.; Evans, J.; Farrar, J.; Fernando, D.; Tran, T.H.; Horstmann, R.; Ibrahim, M.; Karunaweera, N.; Kokwaro, G.; Koram, K.; Kwiatkowski, D.; Lemnge, M.; Makani, J.; Marsh, K.; Michon, P.; Modiano, D.; Molyneux, M.E.; Mueller, I.; Mutabingwa, T.; Parker, M.; Peshu, N.; Plowe, C.; Puijalon, O.; Ragoussis, J.; Reeder, J.; Reyburn, H.; Riley, E.; Rogers, J.; Wilson, M.; Ghansah, A.Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consortial approach that brings together researchers from 21 countries.