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Combining Evidence of Natural Selection with Association Analysis Increases Power to Detect Malaria-Resistance Variants

Ayodo, George ; Price, Alkes L. ; Keinan, Alon ; Ajwang, Arthur ; Otieno, Michael F. ; Orago, Alloys S.S. ; Patterson, Nick ; Reich, David

American journal of human genetics, 2007-08, Vol.81 (2), p.234-242 [Periódico revisado por pares]

Chicago, IL: Elsevier Inc

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Título:
Combining Evidence of Natural Selection with Association Analysis Increases Power to Detect Malaria-Resistance Variants
Autor: Ayodo, George ; Price, Alkes L. ; Keinan, Alon ; Ajwang, Arthur ; Otieno, Michael F. ; Orago, Alloys S.S. ; Patterson, Nick ; Reich, David
Assuntos: Adolescent ; Adult ; Biological and medical sciences ; Biostatistics ; Case-Control Studies ; Child ; Child, Preschool ; Evolution ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Frequency ; General aspects. Genetic counseling ; Genetic Variation ; Genetics of eukaryotes. Biological and molecular evolution ; Human protozoal diseases ; Humans ; Immunity, Innate - genetics ; Infant ; Infectious diseases ; Kenya ; Linkage Disequilibrium ; Malaria ; Malaria - genetics ; Male ; Medical genetics ; Medical sciences ; Molecular and cellular biology ; Parasitic diseases ; Parasitic protozoa ; Protozoal diseases ; Risk factors ; Selection, Genetic ; Statistics as Topic
É parte de: American journal of human genetics, 2007-08, Vol.81 (2), p.234-242
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: 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.
Editor: Chicago, IL: Elsevier Inc
Idioma: Inglês

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Combining Evidence of Natural Selection with Association Analysis Increases Power to Detect Malaria-Resistance Variants

Ayodo, George ; Price, Alkes L. ; Keinan, Alon ; Ajwang, Arthur ; Otieno, Michael F. ; Orago, Alloys S.S. ; Patterson, Nick ; Reich, David

Chicago, IL: Elsevier Inc

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