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

Abstract

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.

Citation

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. (2015). Evidence for Negative Selection at SNPs Increasing Dietary Choline Requirement in a Gambian Cohort. FASEB Journal, 29(8), 3426-35. https://doi.org/10.1096/fj.15-271056

• 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
• Journal: FASEB Journal
• Print ISSN: 0892-6638
• Electronic ISSN: 1530-6860
• Publisher: Federation of American Society of Experimental Biology (FASEB)
• Peer Reviewed: Peer Reviewed
• Volume: 29
• Issue: 8
• Pages: 3426-35
• DOI: https://doi.org/10.1096/fj.15-271056
• Public URL: https://rvc-repository.worktribe.com/output/1401099