Imperial College London
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Professor Thomas N Williams

Faculty of Medicine, Department of Surgery & Cancer

Chair in Haemoglobinopathy Research
 
 
 
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Contact

 

tom.williams Website

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Opi:2018:10.7554/eLife.31579,
author = {Opi, DH and Swann, O and Macharia, A and Uyoga, S and Band, G and Ndila, CM and Harrison, EM and Thera, MA and Kone, AK and Diallo, DA and Doumbo, OK and Lyke, KE and Plowe, CV and Moulds, JM and Shebbe, M and Mturi, N and Peshu, N and Maitland, K and Raza, A and Kwiatkowski, DP and Rockett, KA and Williams, TN and Rowe, JA},
doi = {10.7554/eLife.31579},
journal = {eLife},
title = {Two complement receptor one alleles have opposing associations with cerebral malaria and interact with ethalassaemia},
url = {http://dx.doi.org/10.7554/eLife.31579},
volume = {7},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Malaria has been a major driving force in the evolution of the human genome. In sub-Saharan African populations, two neighbouring polymorphisms in the Complement Receptor One (CR1) gene, named Sl2 and McCb, occur at high frequencies, consistent with selection by malaria. Previous studies have been inconclusive. Using a large case-control study of severe malaria in Kenyan children and statistical models adjusted for confounders, we estimate the relationship between Sl2 and McCb and malaria phenotypes, and find they have opposing associations. The Sl2 polymorphism is associated with markedly reduced odds of cerebral malaria and death, while the McCb polymorphism is associated with increased odds of cerebral malaria. We also identify an apparent interaction between Sl2 and α+thalassaemia, with the protective association of Sl2 greatest in children with normal α-globin. The complex relationship between these three mutations may explain previous conflicting findings, highlighting the importance of considering genetic interactions in disease-association studies.
AU  - Opi,DH
AU  - Swann,O
AU  - Macharia,A
AU  - Uyoga,S
AU  - Band,G
AU  - Ndila,CM
AU  - Harrison,EM
AU  - Thera,MA
AU  - Kone,AK
AU  - Diallo,DA
AU  - Doumbo,OK
AU  - Lyke,KE
AU  - Plowe,CV
AU  - Moulds,JM
AU  - Shebbe,M
AU  - Mturi,N
AU  - Peshu,N
AU  - Maitland,K
AU  - Raza,A
AU  - Kwiatkowski,DP
AU  - Rockett,KA
AU  - Williams,TN
AU  - Rowe,JA
DO  - 10.7554/eLife.31579
PY  - 2018///
SN  - 2050-084X
TI  - Two complement receptor one alleles have opposing associations with cerebral malaria and interact with ethalassaemia
T2  - eLife
UR  - http://dx.doi.org/10.7554/eLife.31579
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000432119300001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/60676
VL  - 7
ER  -
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