Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes

Andrew E. Fry, Anita Ghansa, Kerrin S. Small, Alejandro Palma, Sarah Auburn, Mahamadou Diakite, Angela Green, Susana Campino, Yik Y. Teo, Taane G. Clark, Anna E. Jeffreys, Jonathan Wilson, Muminatou Jallow, Fatou Sisay-Joof, Margaret Pinder, Michael J. Griffiths, Norbert Peshu, Thomas N. Williams, Charles R. Newton, Kevin Marsh & 8 others Malcolm E. Molyneux, Terrie E. Taylor, Kwadwo A. Koram, Abraham R. Oduro, William O. Rogers, Kirk A. Rockett, Pardis C. Sabeti, Dominic P. Kwiatkowski

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The prevalence of CD36 deficiency in East Asian and African populations suggests that the causal variants are under selection by severe malaria. Previous analysis of data from the International HapMap Project indicated that a CD36 haplotype bearing a nonsense mutation (T1264G; rs3211938) had undergone recent positive selection in the Yoruba of Nigeria. To investigate the global distribution of this putative selection event, we genotyped T1264G in 3420 individuals from 66 populations. We confirmed the high frequency of 1264G in the Yoruba (26%). However, the 1264G allele is less common in other African populations and absent from all non-African populations without recent African admixture. Using long-range linkage disequilibrium, we studied two West African groups in depth. Evidence for recent positive selection at the locus was demonstrable in the Yoruba, although not in Gambians. We screened 70 variants from across CD36 for an association with severe malaria phenotypes, employing a case-control study of 1350 subjects and a family study of 1288 parent-offspring trios. No marker was significantly associated with severe malaria. We focused on T1264G, genotyping 10 922 samples from four African populations. The nonsense allele was not associated with severe malaria (pooled allelic odds ratio 1.0; 95% confidence interval 0.89-1.12; P = 0.98). These results suggest a range of possible explanations including the existence of alternative selection pressures on CD36, co-evolution between host and parasite or confounding caused by allelic heterogeneity of CD36 deficiency.

Original languageEnglish
Pages (from-to)2683-2692
Number of pages10
JournalHuman Molecular Genetics
Volume18
Issue number14
DOIs
Publication statusPublished - 2009
Externally publishedYes

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Africa South of the Sahara
Malaria
Phenotype
Population
Alleles
HapMap Project
Nonsense Codon
Linkage Disequilibrium
Nigeria
Haplotypes
Case-Control Studies
Parasites
Odds Ratio
Confidence Intervals
Pressure
Platelet Glycoprotein IV Deficiency

Cite this

Fry, Andrew E. ; Ghansa, Anita ; Small, Kerrin S. ; Palma, Alejandro ; Auburn, Sarah ; Diakite, Mahamadou ; Green, Angela ; Campino, Susana ; Teo, Yik Y. ; Clark, Taane G. ; Jeffreys, Anna E. ; Wilson, Jonathan ; Jallow, Muminatou ; Sisay-Joof, Fatou ; Pinder, Margaret ; Griffiths, Michael J. ; Peshu, Norbert ; Williams, Thomas N. ; Newton, Charles R. ; Marsh, Kevin ; Molyneux, Malcolm E. ; Taylor, Terrie E. ; Koram, Kwadwo A. ; Oduro, Abraham R. ; Rogers, William O. ; Rockett, Kirk A. ; Sabeti, Pardis C. ; Kwiatkowski, Dominic P. / Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes. In: Human Molecular Genetics. 2009 ; Vol. 18, No. 14. pp. 2683-2692.
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title = "Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes",
abstract = "The prevalence of CD36 deficiency in East Asian and African populations suggests that the causal variants are under selection by severe malaria. Previous analysis of data from the International HapMap Project indicated that a CD36 haplotype bearing a nonsense mutation (T1264G; rs3211938) had undergone recent positive selection in the Yoruba of Nigeria. To investigate the global distribution of this putative selection event, we genotyped T1264G in 3420 individuals from 66 populations. We confirmed the high frequency of 1264G in the Yoruba (26{\%}). However, the 1264G allele is less common in other African populations and absent from all non-African populations without recent African admixture. Using long-range linkage disequilibrium, we studied two West African groups in depth. Evidence for recent positive selection at the locus was demonstrable in the Yoruba, although not in Gambians. We screened 70 variants from across CD36 for an association with severe malaria phenotypes, employing a case-control study of 1350 subjects and a family study of 1288 parent-offspring trios. No marker was significantly associated with severe malaria. We focused on T1264G, genotyping 10 922 samples from four African populations. The nonsense allele was not associated with severe malaria (pooled allelic odds ratio 1.0; 95{\%} confidence interval 0.89-1.12; P = 0.98). These results suggest a range of possible explanations including the existence of alternative selection pressures on CD36, co-evolution between host and parasite or confounding caused by allelic heterogeneity of CD36 deficiency.",
author = "Fry, {Andrew E.} and Anita Ghansa and Small, {Kerrin S.} and Alejandro Palma and Sarah Auburn and Mahamadou Diakite and Angela Green and Susana Campino and Teo, {Yik Y.} and Clark, {Taane G.} and Jeffreys, {Anna E.} and Jonathan Wilson and Muminatou Jallow and Fatou Sisay-Joof and Margaret Pinder and Griffiths, {Michael J.} and Norbert Peshu and Williams, {Thomas N.} and Newton, {Charles R.} and Kevin Marsh and Molyneux, {Malcolm E.} and Taylor, {Terrie E.} and Koram, {Kwadwo A.} and Oduro, {Abraham R.} and Rogers, {William O.} and Rockett, {Kirk A.} and Sabeti, {Pardis C.} and Kwiatkowski, {Dominic P.}",
year = "2009",
doi = "10.1093/hmg/ddp192",
language = "English",
volume = "18",
pages = "2683--2692",
journal = "Human Molecular Genetics",
issn = "0964-6906",
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Fry, AE, Ghansa, A, Small, KS, Palma, A, Auburn, S, Diakite, M, Green, A, Campino, S, Teo, YY, Clark, TG, Jeffreys, AE, Wilson, J, Jallow, M, Sisay-Joof, F, Pinder, M, Griffiths, MJ, Peshu, N, Williams, TN, Newton, CR, Marsh, K, Molyneux, ME, Taylor, TE, Koram, KA, Oduro, AR, Rogers, WO, Rockett, KA, Sabeti, PC & Kwiatkowski, DP 2009, 'Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes', Human Molecular Genetics, vol. 18, no. 14, pp. 2683-2692. https://doi.org/10.1093/hmg/ddp192

Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes. / Fry, Andrew E.; Ghansa, Anita; Small, Kerrin S.; Palma, Alejandro; Auburn, Sarah; Diakite, Mahamadou; Green, Angela; Campino, Susana; Teo, Yik Y.; Clark, Taane G.; Jeffreys, Anna E.; Wilson, Jonathan; Jallow, Muminatou; Sisay-Joof, Fatou; Pinder, Margaret; Griffiths, Michael J.; Peshu, Norbert; Williams, Thomas N.; Newton, Charles R.; Marsh, Kevin; Molyneux, Malcolm E.; Taylor, Terrie E.; Koram, Kwadwo A.; Oduro, Abraham R.; Rogers, William O.; Rockett, Kirk A.; Sabeti, Pardis C.; Kwiatkowski, Dominic P.

In: Human Molecular Genetics, Vol. 18, No. 14, 2009, p. 2683-2692.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes

AU - Fry, Andrew E.

AU - Ghansa, Anita

AU - Small, Kerrin S.

AU - Palma, Alejandro

AU - Auburn, Sarah

AU - Diakite, Mahamadou

AU - Green, Angela

AU - Campino, Susana

AU - Teo, Yik Y.

AU - Clark, Taane G.

AU - Jeffreys, Anna E.

AU - Wilson, Jonathan

AU - Jallow, Muminatou

AU - Sisay-Joof, Fatou

AU - Pinder, Margaret

AU - Griffiths, Michael J.

AU - Peshu, Norbert

AU - Williams, Thomas N.

AU - Newton, Charles R.

AU - Marsh, Kevin

AU - Molyneux, Malcolm E.

AU - Taylor, Terrie E.

AU - Koram, Kwadwo A.

AU - Oduro, Abraham R.

AU - Rogers, William O.

AU - Rockett, Kirk A.

AU - Sabeti, Pardis C.

AU - Kwiatkowski, Dominic P.

PY - 2009

Y1 - 2009

N2 - The prevalence of CD36 deficiency in East Asian and African populations suggests that the causal variants are under selection by severe malaria. Previous analysis of data from the International HapMap Project indicated that a CD36 haplotype bearing a nonsense mutation (T1264G; rs3211938) had undergone recent positive selection in the Yoruba of Nigeria. To investigate the global distribution of this putative selection event, we genotyped T1264G in 3420 individuals from 66 populations. We confirmed the high frequency of 1264G in the Yoruba (26%). However, the 1264G allele is less common in other African populations and absent from all non-African populations without recent African admixture. Using long-range linkage disequilibrium, we studied two West African groups in depth. Evidence for recent positive selection at the locus was demonstrable in the Yoruba, although not in Gambians. We screened 70 variants from across CD36 for an association with severe malaria phenotypes, employing a case-control study of 1350 subjects and a family study of 1288 parent-offspring trios. No marker was significantly associated with severe malaria. We focused on T1264G, genotyping 10 922 samples from four African populations. The nonsense allele was not associated with severe malaria (pooled allelic odds ratio 1.0; 95% confidence interval 0.89-1.12; P = 0.98). These results suggest a range of possible explanations including the existence of alternative selection pressures on CD36, co-evolution between host and parasite or confounding caused by allelic heterogeneity of CD36 deficiency.

AB - The prevalence of CD36 deficiency in East Asian and African populations suggests that the causal variants are under selection by severe malaria. Previous analysis of data from the International HapMap Project indicated that a CD36 haplotype bearing a nonsense mutation (T1264G; rs3211938) had undergone recent positive selection in the Yoruba of Nigeria. To investigate the global distribution of this putative selection event, we genotyped T1264G in 3420 individuals from 66 populations. We confirmed the high frequency of 1264G in the Yoruba (26%). However, the 1264G allele is less common in other African populations and absent from all non-African populations without recent African admixture. Using long-range linkage disequilibrium, we studied two West African groups in depth. Evidence for recent positive selection at the locus was demonstrable in the Yoruba, although not in Gambians. We screened 70 variants from across CD36 for an association with severe malaria phenotypes, employing a case-control study of 1350 subjects and a family study of 1288 parent-offspring trios. No marker was significantly associated with severe malaria. We focused on T1264G, genotyping 10 922 samples from four African populations. The nonsense allele was not associated with severe malaria (pooled allelic odds ratio 1.0; 95% confidence interval 0.89-1.12; P = 0.98). These results suggest a range of possible explanations including the existence of alternative selection pressures on CD36, co-evolution between host and parasite or confounding caused by allelic heterogeneity of CD36 deficiency.

UR - http://www.scopus.com/inward/record.url?scp=67650119972&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddp192

DO - 10.1093/hmg/ddp192

M3 - Article

VL - 18

SP - 2683

EP - 2692

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 14

ER -