作者
Muminatou Jallow, Yik Ying Teo, Kerrin S Small, Kirk A Rockett, Panos Deloukas, Taane G Clark, Katja Kivinen, Kalifa A Bojang, David J Conway, Margaret Pinder, Giorgio Sirugo, Fatou Sisay-Joof, Stanley Usen, Sarah Auburn, Suzannah J Bumpstead, Susana Campino, Alison Coffey, Andrew Dunham, Andrew E Fry, Angela Green, Rhian Gwilliam, Sarah E Hunt, Michael Inouye, Anna E Jeffreys, Alieu Mendy, Aarno Palotie, Simon Potter, Jiannis Ragoussis, Jane Rogers, Kate Rowlands, Elilan Somaskantharajah, Pamela Whittaker, Claire Widden, Peter Donnelly, Bryan Howie, Jonathan Marchini, Andrew Morris, Miguel SanJoaquin, Eric Akum Achidi, Tsiri Agbenyega, Angela Allen, Olukemi Amodu, Patrick Corran, Abdoulaye Djimde, Amagana Dolo, Ogobara K Doumbo, Chris Drakeley, Sarah Dunstan, Jennifer Evans, Jeremy Farrar, Deepika Fernando, Tran Tinh Hien, Rolf D Horstmann, Muntaser Ibrahim, Nadira Karunaweera, Gilbert Kokwaro, Kwadwo A Koram, Martha Lemnge, Julie Makani, Kevin Marsh, Pascal Michon, David Modiano, Malcolm E Molyneux, Ivo Mueller, Michael Parker, Norbert Peshu, Christopher V Plowe, Odile Puijalon, John Reeder, Hugh Reyburn, Eleanor M Riley, Anavaj Sakuntabhai, Pratap Singhasivanon, Sodiomon Sirima, Adama Tall, Terrie E Taylor, Mahamadou Thera, Marita Troye-Blomberg, Thomas N Williams, Michael Wilson, Dominic P Kwiatkowski, Wellcome Trust Case Control Consortium, Malaria Genomic Epidemiology Network
发表日期
2009/6
期刊
Nature genetics
卷号
41
期号
6
页码范围
657-665
出版商
Nature Publishing Group US
简介
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 …
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M Jallow, YY Teo, KS Small, KA Rockett, P Deloukas… - Nature genetics, 2009
