Dietary intake of one-carbon metabolism nutrients and DNA methylation in peripheral blood

James A. Chamberlain, Pierre Antoine Dugué, Julie K. Bassett, Allison M. Hodge, Maree T. Brinkman, Ji Hoon E. Joo, Chol Hee Jung, Enes Makalic, Daniel F. Schmidt, John L. Hopper, Daniel D. Buchanan, Dallas R. English, Melissa C. Southey, Graham G. Giles, Roger L. Milne

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Folate and other one-carbon metabolism nutrients are essential to enable DNA methylation to occur, but the extent to which their dietary intake influences methylation in adulthood is unclear. Objective: We assessed associations between dietary intake of these nutrients and DNA methylation in peripheral blood, overall and at specific genomic locations. Design: We conducted a cross-sectional study using baseline data and samples from 5186 adult participants in the Melbourne Collaborative Cohort Study (MCCS). Nutrient intake was estimated from a food-frequency questionnaire. DNA methylation was measured by using the Illumina Infinium HumanMethylation450 BeadChip array (HM450K). We assessed associations of intakes of folate, riboflavin, vitamins B-6 and B-12, methionine, choline, and betaine with methylation at individual cytosine-guanine dinucleotides (CpGs), and with median (genome-wide) methylation across all CpGs, CpGs in gene bodies, and CpGs in gene promoters. We also assessed associations with methylation at long interspersed nuclear element 1 (LINE-1), satellite 2 (Sat2), and Arthrobacter luteus restriction endonuclease (Alu) repetitive elements for a subset of participants. We used linear mixed regression, adjusting for age, sex, country of birth, smoking, energy intake from food, alcohol intake, Mediterranean diet score, and batch effects to assess log-linear associations with dietary intake of each nutrient. In secondary analyses, we assessed associations with low or high intakes defined by extreme quintiles. Results: No evidence of log-linear association was observed at P < 10-7 between the intake of one-carbon metabolism nutrients and methylation at individual CpGs. Low intake of riboflavin was associated with higher methylation at CpG cg21230392 in the first exon of PROM1 (P = 5.0 × 10-8). No consistent evidence of association was observed with genome-wide or repetitive element measures of methylation. Conclusion: Our findings suggest that dietary intake of one-carbon metabolism nutrients in adulthood, as measured by a food-frequency questionnaire, has little association with blood DNA methylation. An association with low intake of riboflavin requires replication in independent cohorts.

Original languageEnglish
Pages (from-to)611-621
Number of pages11
JournalAmerican Journal of Clinical Nutrition
Volume108
Issue number3
DOIs
Publication statusPublished - 1 Sep 2018
Externally publishedYes

Keywords

  • B vitamins
  • DNA methylation
  • epigenetics
  • folate
  • one-carbon metabolism

Cite this

Chamberlain, James A. ; Dugué, Pierre Antoine ; Bassett, Julie K. ; Hodge, Allison M. ; Brinkman, Maree T. ; Joo, Ji Hoon E. ; Jung, Chol Hee ; Makalic, Enes ; Schmidt, Daniel F. ; Hopper, John L. ; Buchanan, Daniel D. ; English, Dallas R. ; Southey, Melissa C. ; Giles, Graham G. ; Milne, Roger L. / Dietary intake of one-carbon metabolism nutrients and DNA methylation in peripheral blood. In: American Journal of Clinical Nutrition. 2018 ; Vol. 108, No. 3. pp. 611-621.
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abstract = "Background: Folate and other one-carbon metabolism nutrients are essential to enable DNA methylation to occur, but the extent to which their dietary intake influences methylation in adulthood is unclear. Objective: We assessed associations between dietary intake of these nutrients and DNA methylation in peripheral blood, overall and at specific genomic locations. Design: We conducted a cross-sectional study using baseline data and samples from 5186 adult participants in the Melbourne Collaborative Cohort Study (MCCS). Nutrient intake was estimated from a food-frequency questionnaire. DNA methylation was measured by using the Illumina Infinium HumanMethylation450 BeadChip array (HM450K). We assessed associations of intakes of folate, riboflavin, vitamins B-6 and B-12, methionine, choline, and betaine with methylation at individual cytosine-guanine dinucleotides (CpGs), and with median (genome-wide) methylation across all CpGs, CpGs in gene bodies, and CpGs in gene promoters. We also assessed associations with methylation at long interspersed nuclear element 1 (LINE-1), satellite 2 (Sat2), and Arthrobacter luteus restriction endonuclease (Alu) repetitive elements for a subset of participants. We used linear mixed regression, adjusting for age, sex, country of birth, smoking, energy intake from food, alcohol intake, Mediterranean diet score, and batch effects to assess log-linear associations with dietary intake of each nutrient. In secondary analyses, we assessed associations with low or high intakes defined by extreme quintiles. Results: No evidence of log-linear association was observed at P < 10-7 between the intake of one-carbon metabolism nutrients and methylation at individual CpGs. Low intake of riboflavin was associated with higher methylation at CpG cg21230392 in the first exon of PROM1 (P = 5.0 × 10-8). No consistent evidence of association was observed with genome-wide or repetitive element measures of methylation. Conclusion: Our findings suggest that dietary intake of one-carbon metabolism nutrients in adulthood, as measured by a food-frequency questionnaire, has little association with blood DNA methylation. An association with low intake of riboflavin requires replication in independent cohorts.",
keywords = "B vitamins, DNA methylation, epigenetics, folate, one-carbon metabolism",
author = "Chamberlain, {James A.} and Dugu{\'e}, {Pierre Antoine} and Bassett, {Julie K.} and Hodge, {Allison M.} and Brinkman, {Maree T.} and Joo, {Ji Hoon E.} and Jung, {Chol Hee} and Enes Makalic and Schmidt, {Daniel F.} and Hopper, {John L.} and Buchanan, {Daniel D.} and English, {Dallas R.} and Southey, {Melissa C.} and Giles, {Graham G.} and Milne, {Roger L.}",
note = "Chamberlain, James A Dugue, Pierre-Antoine Bassett, Julie K Hodge, Allison M Brinkman, Maree T Joo, JiHoon E Jung, Chol-Hee Makalic, Enes Schmidt, Daniel F Hopper, John L Buchanan, Daniel D English, Dallas R Southey, Melissa C Giles, Graham G Milne, Roger L eng 2018/08/14 06:00 Am J Clin Nutr. 2018 Sep 1;108(3):611-621. doi: 10.1093/ajcn/nqy119.",
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Chamberlain, JA, Dugué, PA, Bassett, JK, Hodge, AM, Brinkman, MT, Joo, JHE, Jung, CH, Makalic, E, Schmidt, DF, Hopper, JL, Buchanan, DD, English, DR, Southey, MC, Giles, GG & Milne, RL 2018, 'Dietary intake of one-carbon metabolism nutrients and DNA methylation in peripheral blood' American Journal of Clinical Nutrition, vol. 108, no. 3, pp. 611-621. https://doi.org/10.1093/ajcn/nqy119

Dietary intake of one-carbon metabolism nutrients and DNA methylation in peripheral blood. / Chamberlain, James A.; Dugué, Pierre Antoine; Bassett, Julie K.; Hodge, Allison M.; Brinkman, Maree T.; Joo, Ji Hoon E.; Jung, Chol Hee; Makalic, Enes; Schmidt, Daniel F.; Hopper, John L.; Buchanan, Daniel D.; English, Dallas R.; Southey, Melissa C.; Giles, Graham G.; Milne, Roger L.

In: American Journal of Clinical Nutrition, Vol. 108, No. 3, 01.09.2018, p. 611-621.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Dietary intake of one-carbon metabolism nutrients and DNA methylation in peripheral blood

AU - Chamberlain, James A.

AU - Dugué, Pierre Antoine

AU - Bassett, Julie K.

AU - Hodge, Allison M.

AU - Brinkman, Maree T.

AU - Joo, Ji Hoon E.

AU - Jung, Chol Hee

AU - Makalic, Enes

AU - Schmidt, Daniel F.

AU - Hopper, John L.

AU - Buchanan, Daniel D.

AU - English, Dallas R.

AU - Southey, Melissa C.

AU - Giles, Graham G.

AU - Milne, Roger L.

N1 - Chamberlain, James A Dugue, Pierre-Antoine Bassett, Julie K Hodge, Allison M Brinkman, Maree T Joo, JiHoon E Jung, Chol-Hee Makalic, Enes Schmidt, Daniel F Hopper, John L Buchanan, Daniel D English, Dallas R Southey, Melissa C Giles, Graham G Milne, Roger L eng 2018/08/14 06:00 Am J Clin Nutr. 2018 Sep 1;108(3):611-621. doi: 10.1093/ajcn/nqy119.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Background: Folate and other one-carbon metabolism nutrients are essential to enable DNA methylation to occur, but the extent to which their dietary intake influences methylation in adulthood is unclear. Objective: We assessed associations between dietary intake of these nutrients and DNA methylation in peripheral blood, overall and at specific genomic locations. Design: We conducted a cross-sectional study using baseline data and samples from 5186 adult participants in the Melbourne Collaborative Cohort Study (MCCS). Nutrient intake was estimated from a food-frequency questionnaire. DNA methylation was measured by using the Illumina Infinium HumanMethylation450 BeadChip array (HM450K). We assessed associations of intakes of folate, riboflavin, vitamins B-6 and B-12, methionine, choline, and betaine with methylation at individual cytosine-guanine dinucleotides (CpGs), and with median (genome-wide) methylation across all CpGs, CpGs in gene bodies, and CpGs in gene promoters. We also assessed associations with methylation at long interspersed nuclear element 1 (LINE-1), satellite 2 (Sat2), and Arthrobacter luteus restriction endonuclease (Alu) repetitive elements for a subset of participants. We used linear mixed regression, adjusting for age, sex, country of birth, smoking, energy intake from food, alcohol intake, Mediterranean diet score, and batch effects to assess log-linear associations with dietary intake of each nutrient. In secondary analyses, we assessed associations with low or high intakes defined by extreme quintiles. Results: No evidence of log-linear association was observed at P < 10-7 between the intake of one-carbon metabolism nutrients and methylation at individual CpGs. Low intake of riboflavin was associated with higher methylation at CpG cg21230392 in the first exon of PROM1 (P = 5.0 × 10-8). No consistent evidence of association was observed with genome-wide or repetitive element measures of methylation. Conclusion: Our findings suggest that dietary intake of one-carbon metabolism nutrients in adulthood, as measured by a food-frequency questionnaire, has little association with blood DNA methylation. An association with low intake of riboflavin requires replication in independent cohorts.

AB - Background: Folate and other one-carbon metabolism nutrients are essential to enable DNA methylation to occur, but the extent to which their dietary intake influences methylation in adulthood is unclear. Objective: We assessed associations between dietary intake of these nutrients and DNA methylation in peripheral blood, overall and at specific genomic locations. Design: We conducted a cross-sectional study using baseline data and samples from 5186 adult participants in the Melbourne Collaborative Cohort Study (MCCS). Nutrient intake was estimated from a food-frequency questionnaire. DNA methylation was measured by using the Illumina Infinium HumanMethylation450 BeadChip array (HM450K). We assessed associations of intakes of folate, riboflavin, vitamins B-6 and B-12, methionine, choline, and betaine with methylation at individual cytosine-guanine dinucleotides (CpGs), and with median (genome-wide) methylation across all CpGs, CpGs in gene bodies, and CpGs in gene promoters. We also assessed associations with methylation at long interspersed nuclear element 1 (LINE-1), satellite 2 (Sat2), and Arthrobacter luteus restriction endonuclease (Alu) repetitive elements for a subset of participants. We used linear mixed regression, adjusting for age, sex, country of birth, smoking, energy intake from food, alcohol intake, Mediterranean diet score, and batch effects to assess log-linear associations with dietary intake of each nutrient. In secondary analyses, we assessed associations with low or high intakes defined by extreme quintiles. Results: No evidence of log-linear association was observed at P < 10-7 between the intake of one-carbon metabolism nutrients and methylation at individual CpGs. Low intake of riboflavin was associated with higher methylation at CpG cg21230392 in the first exon of PROM1 (P = 5.0 × 10-8). No consistent evidence of association was observed with genome-wide or repetitive element measures of methylation. Conclusion: Our findings suggest that dietary intake of one-carbon metabolism nutrients in adulthood, as measured by a food-frequency questionnaire, has little association with blood DNA methylation. An association with low intake of riboflavin requires replication in independent cohorts.

KW - B vitamins

KW - DNA methylation

KW - epigenetics

KW - folate

KW - one-carbon metabolism

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