Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Genet. 2009 Jun;41(6):657-65. doi: 10.1038/ng.388. Epub 2009 May 24.

Genome-wide and fine-resolution association analysis of malaria in West Africa.

Collaborators (374)

Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Samani NJ, Todd JA, Donnelly P, Barrett JC, Burton PR, Davison D, Donnelly P, Easton D, Evans D, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Cardon LR, Clayton DG, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Todd JA, Ouwehand WH, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon-Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskvina V, Nikolov I, O'Donovan MC, Owen MJ, Craddock N, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Ball SG, Balmforth AJ, Barrett JH, Bishop DT, Iles MM, Maqbool A, Yuldasheva N, Hall AS, Braund PS, Burton PR, Dixon RJ, Mangino M, Stevens S, Tobin MD, Thompson JR, Samani NJ, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Mathew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP, Webster J, Brown MJ, Clayton DG, Lathrop GM, Connell J, Dominiczak A, Samani NJ, Braga Marcano CA, Burke B, Dobson R, Gungadoo J, Lee KL, Munroe PB, Newhouse SJ, Onipinla A, Wallace C, Xue M, Caulfield M, Farrall M, Barton A, Bruce IN, Donovan H, Eyre S, Gilbert PD, Hider SL, Hinks AM, John SL, Potter C, Silman AJ, Symmons DP, Thomson W, Worthington J, Clayton DG, Dunger DB, Nutland S, Stevens HE, Walker NM, Widmer B, Todd JA, Frayling TM, Freathy RM, Lango H, Perry JR, Shields BM, Weedon MN, Hattersley AT, Hitman GA, Walker M, Elliott KS, Groves CJ, Lindgren CM, Rayner NW, Timpson NJ, Zeggini E, McCarthy MI, Bradbury LA, Farrar C, Pointon JJ, Wordsworth P, Brown MA, Franklyn JA, Heward JM, Simmonds MJ, Gough SC, Seal S, Stratton MR, Rahman N, Ban M, Goris A, Sawcer SJ, Compston A, Conway D, Jallow M, Newport M, Sirugo G, Walton R, Rockett KA, Kwiatkowski DP, Bryan C, Bumpstead SJ, Chaney A, Downes K, Ghori J, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Withers D, Deloukas P, Leung HT, Nutland S, Stevens HE, Walker NM, Todd JA, Easton D, Clayton DG, Burton PR, Tobin MD, Barrett JC, Evans D, Morris AP, Cardon LR, Cardin NJ, Davison D, Ferreira T, Pereira-Gale J, Hallgrimsdóttir IB, Howie BN, Marchini JL, Spencer CC, Su Z, Teo YY, Vukcevic D, Donnelly P, Bentley D, Brown MA, Cardon LR, Caulfield M, Clayton DG, Compston DA, Craddock N, Deloukas P, Donnelly P, Farrall M, Gough SC, Hall AS, Hattersley AT, Hill AV, Kwiatkowski DP, Mathew CG, McCarthy MI, Ouwehand WH, Parkes M, Pembrey M, Rahman N, Samani NJ, Stratton MR, Todd JA, Worthington J, Achidi EA, 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, Hien TT, Horstmann R, Ibrahim M, Karunaweera N, Kokwaro G, Koram K, Kwiatkowski D, Lemnge M, Makani J, Marsh K, Michon P, Modiano D, Molyneux ME, Mueller I, Mutabingwa T, Parker M, Peshu N, Plowe C, Puijalon O, Ragoussis J, Reeder J, Reyburn H, Riley E, Rogers J, Sakuntabhai A, Singhasivanon P, Sirima S, Sirugo G, Tall A, Taylor T, Thera M, Troye-Blomberg M, Williams T, Wilson M, Amenga-Etego L, Apinjoh TO, Bougouma E, Dewasurendra R, Diakite M, Enimil A, Hussein A, Ishengoma D, Jallow M, Lin E, Ly A, Mangano VD, Manjurano A, Manning L, Ndila CM, Nyirongo V, Oluoch T, Quyen NT, Suriyaphol P, Toure O, Rockett KA, Vanderwal A, Clark T, Parker M, Wrigley R, Kwiatkowski D, Alcock D, Auburn S, Barnwell D, Bull S, Campino S, deVries J, Elzein A, Evans J, Fitzpatrick K, Ghansah A, Green A, Hart L, Hilton E, Hubbart C, Hughes C, Jeffreys AE, Kivinen K, MacInnis B, Manske M, Maslen G, McCreight M, Mendy A, Moyes C, Potter C, Risley P, Rowlands K, SanJoaquin M, Small KS, Somaskantharajah E, Stevens M, Teo Y, Watson R, Agbenyega T, Carucci D, Cook K, Doyle A, Duombo O, Farrar J, Gottlieb M, Marsh K, Puijalon O, Taylor T, Kwiatkowski D.

Author information

  • 1MRC Laboratories, Fajara, Banjul, Gambia.

Abstract

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.

PMID:
19465909
[PubMed - indexed for MEDLINE]
PMCID:
PMC2889040
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Publication Types, MeSH Terms, Substances, Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk