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Evidence for Negative Selection at SNPs Increasing Dietary Choline Requirement in a Gambian Cohort

Silver, M J; Corbin, K D; Hellenthal, G; Da Costa, K A; Dominguez-Salas, P; Moore, S E; Owen, J; Prentice, A M; Hennig, B J; Zeishel, S H


M J Silver

K D Corbin

G Hellenthal

K A Da Costa

P Dominguez-Salas

S E Moore

J Owen

A M Prentice

B J Hennig

S H Zeishel


Choline is an essential nutrient, and the amount needed in the diet is modulated by several factors. Given geographical differences in dietary choline intake and disparate frequencies of single-nucleotide polymorphisms (SNPs) in choline metabolism genes between ethnic groups, we tested the hypothesis that 3 SNPs that increase dependence on dietary choline would be under negative selection pressure in settings where choline intake is low: choline dehydrogenase (CHDH) rs12676, methylenetetrahydrofolate reductase 1 (MTHFD1) rs2236225, and phosphatidylethanolamine-N-methyltransferase (PEMT) rs12325817. Evidence of negative selection was assessed in 2 populations: one in The Gambia, West Africa, where there is historic evidence of a choline-poor diet, and the other in the United States, with a comparatively choline-rich diet. We used 2 independent methods, and confirmation of our hypothesis was sought via a comparison with SNP data from the Maasai, an East African population with a genetic background similar to that of Gambians but with a traditional diet that is higher in choline. Our results show that frequencies of SNPs known to increase dependence on dietary choline are significantly reduced in the low-choline setting of The Gambia. Our findings suggest that adequate intake levels of choline may have to be reevaluated in different ethnic groups and highlight a possible approach for identifying novel functional SNPs under the influence of dietary selective pressure.


Silver, M. J., Corbin, K. D., Hellenthal, G., Da Costa, K. A., Dominguez-Salas, P., Moore, S. E., …Zeishel, S. H. (2015). Evidence for Negative Selection at SNPs Increasing Dietary Choline Requirement in a Gambian Cohort. FASEB Journal, 29(8), 3426-35.

Journal Article Type Article
Acceptance Date Apr 16, 2015
Publication Date Apr 28, 2015
Deposit Date Aug 20, 2015
Publicly Available Date Jan 23, 2019
Print ISSN 0892-6638
Publisher Federation of American Society of Experimental Biology (FASEB)
Peer Reviewed Peer Reviewed
Volume 29
Issue 8
Pages 3426-35
Public URL


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