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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Combining evidence of natural selection with association analysis increases power to detect malaria-resistance variants
American Journal of Human Genetics, Volume 81, No. 2, Year 2007
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Description
Statistical power to detect disease variants can be increased by weighting candidates by their evidence of natural selection. To demonstrate that this theoretical idea works in practice, we performed an association study of 10 putative resistance variants in 471 severe malaria cases and 474 controls from the Luo in Kenya. We replicated associations at HBB (P = .0008) and CD36 (P = .03) but also showed that the same variants are unusually differentiated in frequency between the Luo and Yoruba (who historically have been exposed to malaria) and the Masai and Kikuyu (who have not been exposed). This empirically demonstrates that combining association analysis with evidence of natural selection can increase power to detect risk variants by orders of magnitude - up to P = .000018 for HBB and P = .00043 for CD36. © 2007 by The American Society of Human Genetics. All rights reserved.
Authors & Co-Authors
Ayodo, George A.
United States, Cambridge
Broad Institute
Price, Alkes L.
United States, Cambridge
Broad Institute
Keinan, Alon
United States, Cambridge
Broad Institute
Ajwang, Arthur
Kenya, Nairobi
Kenyatta University
Otieno, Michael F.
Kenya, Nairobi
Kenyatta University
Orago, Alloys S.S.
Kenya, Nairobi
Kenyatta University
Patterson, Nick J.
United States, Cambridge
Broad Institute
Reich, David E.
United States, Cambridge
Broad Institute
United States, Boston
Harvard Medical School
Statistics
Citations: 83
Authors: 8
Affiliations: 3
Identifiers
Doi:
10.1086/519221
ISSN:
00029297
Research Areas
Genetics And Genomics
Infectious Diseases
Study Locations
Kenya