Evidence for negative selection of gene variants that increase dependence on dietary choline in a Gambian cohort.
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.
*Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council Unit, Banjul, The Gambia; Nutrition Research Institute, North Carolina Research Campus, Kannapolis, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University College London Genetics Institute, University College London, United Kingdom; Toxicology Services, Incorporated, Chapel Hill, North Carolina, USA; and Maternal and Child Nutrition Group, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.
Matt J
MJ
Silver
*Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council Unit, Banjul, The Gambia; Nutrition Research Institute, North Carolina Research Campus, Kannapolis, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University College London Genetics Institute, University College London, United Kingdom; Toxicology Services, Incorporated, Chapel Hill, North Carolina, USA; and Maternal and Child Nutrition Group, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.
Karen D
KD
Corbin
*Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council Unit, Banjul, The Gambia; Nutrition Research Institute, North Carolina Research Campus, Kannapolis, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University College London Genetics Institute, University College London, United Kingdom; Toxicology Services, Incorporated, Chapel Hill, North Carolina, USA; and Maternal and Child Nutrition Group, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.
Garrett
G
Hellenthal
*Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council Unit, Banjul, The Gambia; Nutrition Research Institute, North Carolina Research Campus, Kannapolis, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University College London Genetics Institute, University College London, United Kingdom; Toxicology Services, Incorporated, Chapel Hill, North Carolina, USA; and Maternal and Child Nutrition Group, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.
Kerry-Ann
KA
da Costa
*Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council Unit, Banjul, The Gambia; Nutrition Research Institute, North Carolina Research Campus, Kannapolis, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University College London Genetics Institute, University College London, United Kingdom; Toxicology Services, Incorporated, Chapel Hill, North Carolina, USA; and Maternal and Child Nutrition Group, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.
Paula
P
Dominguez-Salas
*Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council Unit, Banjul, The Gambia; Nutrition Research Institute, North Carolina Research Campus, Kannapolis, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University College London Genetics Institute, University College London, United Kingdom; Toxicology Services, Incorporated, Chapel Hill, North Carolina, USA; and Maternal and Child Nutrition Group, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.
Sophie E
SE
Moore
*Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council Unit, Banjul, The Gambia; Nutrition Research Institute, North Carolina Research Campus, Kannapolis, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University College London Genetics Institute, University College London, United Kingdom; Toxicology Services, Incorporated, Chapel Hill, North Carolina, USA; and Maternal and Child Nutrition Group, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.
Jennifer
J
Owen
*Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council Unit, Banjul, The Gambia; Nutrition Research Institute, North Carolina Research Campus, Kannapolis, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University College London Genetics Institute, University College London, United Kingdom; Toxicology Services, Incorporated, Chapel Hill, North Carolina, USA; and Maternal and Child Nutrition Group, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.
Andrew M
AM
Prentice
*Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council Unit, Banjul, The Gambia; Nutrition Research Institute, North Carolina Research Campus, Kannapolis, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University College London Genetics Institute, University College London, United Kingdom; Toxicology Services, Incorporated, Chapel Hill, North Carolina, USA; and Maternal and Child Nutrition Group, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.
Branwen J
BJ
Hennig
*Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council Unit, Banjul, The Gambia; Nutrition Research Institute, North Carolina Research Campus, Kannapolis, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University College London Genetics Institute, University College London, United Kingdom; Toxicology Services, Incorporated, Chapel Hill, North Carolina, USA; and Maternal and Child Nutrition Group, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom steven_zeisel@unc.edu.
Steven H
SH
Zeisel
D002794:Choline / Q000235:genetics* / Q000378:metabolism*; D050545:Choline Dehydrogenase / Q000235:genetics / Q000378:metabolism; D004032:Diet / Q000379:methods; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D050545:Choline Dehydrogenase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D050918:Phosphatidylethanolamine N-Methyltransferase; D002794:Choline
adequate intake levels; choline dehydrogenase; diet and selection; methylenetetrahydrofolate dehydrogenase; phosphatidylethanolamine-N-methyltransferase