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Accumulating evidence suggests that early-life nutrition can affect metabolism and thus increase the risk of disease in adulthood (e.g. type II diabetes and obesity). One possible mechanism to explain these effects is epigenetic variation at critical periods of development. Epigenetic variation describes non-inherited permanent alterations to an individuals DNA.
Recent work in mouse models has demonstrated that maternal nutritional status can affect such epigenetic processes such as DNA methylation and gene expression during embryonic development, with profound effects on outcomes. The investigators aim to study these processes in humans for the first time. The investigators will exploit the "experiment of nature" setting in The Gambia, i.e. fluctuation in diet according to season. During the 'hungry' season diets are known to be depleted in nutrients required for epigenetic gene regulation. Nutritional biomarkers in blood as well as the dietary intake will be measured in pregnant women according to season. A blood sample will also be taken from babies born to these women to determine whether there is a direct effect of diet on mothers' nutritional status and hence variation in DNA methylation patterns in their babies by season.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| maternal methyl-donors, infant epigenetics | women of reproductive age in rural Gambia, infants born to these women |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| season, dietary intake | Other |
|
| Measure | Description | Time Frame |
|---|---|---|
| DNA methylation of infants | Measurement of DNA methylation of infants recruited into the study, at 3-6 months of age. Measurement of blood biomarkers monthly after dietary assessment or in early pregnancy | infants: at 3-6 months of age |
| Measure | Description | Time Frame |
|---|---|---|
| Blood biomarker status of women | Measurement of blood biomarkers monthly after dietary assessment or in early pregnancy | monthly for 12 months or in early pregnancy |
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Inclusion criteria women:
- women aged 18-45 years on 15th March 2009, resident in West Kiang
Exclusion criteria women:
Inclusion criteria infants:
- born to the above women
Exclusion criteria infants:
- those known to be severely malnourished (weight-for-height Z-score < -3)
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women of reproductive age in rural Gambia and their infants
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24781383 | Result | Dominguez-Salas P, Moore SE, Baker MS, Bergen AW, Cox SE, Dyer RA, Fulford AJ, Guan Y, Laritsky E, Silver MJ, Swan GE, Zeisel SH, Innis SM, Waterland RA, Prentice AM, Hennig BJ. Maternal nutrition at conception modulates DNA methylation of human metastable epialleles. Nat Commun. 2014 Apr 29;5:3746. doi: 10.1038/ncomms4746. | |
| 26062908 |
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| ID | Term |
|---|---|
| D012621 | Seasons |
| D004435 | Eating |
| ID | Term |
|---|---|
| D010507 | Periodicity |
| D013995 | Time |
| D055585 | Physical Phenomena |
| D002980 | Climate |
| D004777 |
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blood, buccal swab, hair follicles
| Silver MJ, Kessler NJ, Hennig BJ, Dominguez-Salas P, Laritsky E, Baker MS, Coarfa C, Hernandez-Vargas H, Castelino JM, Routledge MN, Gong YY, Herceg Z, Lee YS, Lee K, Moore SE, Fulford AJ, Prentice AM, Waterland RA. Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment. Genome Biol. 2015 Jun 11;16(1):118. doi: 10.1186/s13059-015-0660-y. |
| 23576045 | Derived | Dominguez-Salas P, Moore SE, Cole D, da Costa KA, Cox SE, Dyer RA, Fulford AJ, Innis SM, Waterland RA, Zeisel SH, Prentice AM, Hennig BJ. DNA methylation potential: dietary intake and blood concentrations of one-carbon metabolites and cofactors in rural African women. Am J Clin Nutr. 2013 Jun;97(6):1217-27. doi: 10.3945/ajcn.112.048462. Epub 2013 Apr 10. |
| Environment |
| D055669 | Ecological and Environmental Phenomena |
| D001686 | Biological Phenomena |
| D001272 | Atmosphere |
| D008685 | Meteorological Concepts |
| D004778 | Environment and Public Health |
| D009747 | Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D004068 | Digestive System Physiological Phenomena |
| D055688 | Digestive System and Oral Physiological Phenomena |