Genome-wide average DNA methylation is determined in utero

Shuai Li, Ee Ming Wong, Pierre Antoine Dugué, Allan McRae, Eunae Kim, Jihoon Eric Joo, Tuong L. Nguyen, Jennifer L Stone, Gillian S Dite, Nicola Armstrong, Karen A Mather, Anbupalam Thalamuthu, Margaret J Wright, David J Ames, Roger L. Milne, Jeffrey Mark Craig, Richard Saffery, Grant W Montgomery, Yun Mi Song, Joohon Sung & 5 others Timothy D Spector, Perminder Singh Sachdev, Graham Gerald Giles, Melissa Caroline Southey, John L Hopper

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Investigating the genetic and environmental causes of variation in genome-wide average DNA methylation (GWAM), a global methylation measure from the HumanMethylation450 array, might give a better understanding of genetic and environmental influences on methylation. Methods: We measured GWAM for 2299 individuals aged 0 to 90 years from seven twin and/or family studies. We estimated familial correlations, modelled correlations with cohabitation history and fitted variance components models for GWAM. Results: The correlation in GWAM for twin pairs was 0.8 at birth, decreased with age during adolescence and was constant at 0.4 throughout adulthood, with no evidence that twin pair correlations differed by zygosity. Non-twin first-degree relatives were correlated, from 0.17 [95% confidence interval (CI): 0.05–0.30] to 0.28 (95% CI: 0.08–0.48), except for middle-aged siblings (0.01, 95% CI: 0.10–0.12), and the correlation increased with time living together and decreased with time living apart. Spouse pairs were correlated in all studies, from 0.23 (95% CI: 0.3–0.43) to 0.31 (95% CI: 0.05–0.52), and the correlation increased with time living together. The variance explained by environmental factors shared by twins alone was 90% (95% CI: 74–95%) at birth, decreased in early life and plateaued at 28% (95% CI: 17–39%) in middle age and beyond. There was a cohabitation-related environmental component of variance. Conclusions: GWAM is determined in utero by prenatal environmental factors, the effects of which persist throughout life. The variation of GWAM is also influenced by environmental factors shared by family members, as well as by individual-specific environmental factors.

Original languageEnglish
Pages (from-to)908-916
Number of pages9
JournalInternational Journal of Epidemiology
Volume47
Issue number3
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

  • DNA methylation
  • Epigenomics
  • Twin study

Cite this

Li, Shuai ; Wong, Ee Ming ; Dugué, Pierre Antoine ; McRae, Allan ; Kim, Eunae ; Joo, Jihoon Eric ; Nguyen, Tuong L. ; Stone, Jennifer L ; Dite, Gillian S ; Armstrong, Nicola ; Mather, Karen A ; Thalamuthu, Anbupalam ; Wright, Margaret J ; Ames, David J ; Milne, Roger L. ; Craig, Jeffrey Mark ; Saffery, Richard ; Montgomery, Grant W ; Song, Yun Mi ; Sung, Joohon ; Spector, Timothy D ; Sachdev, Perminder Singh ; Giles, Graham Gerald ; Southey, Melissa Caroline ; Hopper, John L. / Genome-wide average DNA methylation is determined in utero. In: International Journal of Epidemiology. 2018 ; Vol. 47, No. 3. pp. 908-916.
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title = "Genome-wide average DNA methylation is determined in utero",
abstract = "Background: Investigating the genetic and environmental causes of variation in genome-wide average DNA methylation (GWAM), a global methylation measure from the HumanMethylation450 array, might give a better understanding of genetic and environmental influences on methylation. Methods: We measured GWAM for 2299 individuals aged 0 to 90 years from seven twin and/or family studies. We estimated familial correlations, modelled correlations with cohabitation history and fitted variance components models for GWAM. Results: The correlation in GWAM for twin pairs was 0.8 at birth, decreased with age during adolescence and was constant at 0.4 throughout adulthood, with no evidence that twin pair correlations differed by zygosity. Non-twin first-degree relatives were correlated, from 0.17 [95{\%} confidence interval (CI): 0.05–0.30] to 0.28 (95{\%} CI: 0.08–0.48), except for middle-aged siblings (0.01, 95{\%} CI: 0.10–0.12), and the correlation increased with time living together and decreased with time living apart. Spouse pairs were correlated in all studies, from 0.23 (95{\%} CI: 0.3–0.43) to 0.31 (95{\%} CI: 0.05–0.52), and the correlation increased with time living together. The variance explained by environmental factors shared by twins alone was 90{\%} (95{\%} CI: 74–95{\%}) at birth, decreased in early life and plateaued at 28{\%} (95{\%} CI: 17–39{\%}) in middle age and beyond. There was a cohabitation-related environmental component of variance. Conclusions: GWAM is determined in utero by prenatal environmental factors, the effects of which persist throughout life. The variation of GWAM is also influenced by environmental factors shared by family members, as well as by individual-specific environmental factors.",
keywords = "DNA methylation, Epigenomics, Twin study",
author = "Shuai Li and Wong, {Ee Ming} and Dugu{\'e}, {Pierre Antoine} and Allan McRae and Eunae Kim and Joo, {Jihoon Eric} and Nguyen, {Tuong L.} and Stone, {Jennifer L} and Dite, {Gillian S} and Nicola Armstrong and Mather, {Karen A} and Anbupalam Thalamuthu and Wright, {Margaret J} and Ames, {David J} and Milne, {Roger L.} and Craig, {Jeffrey Mark} and Richard Saffery and Montgomery, {Grant W} and Song, {Yun Mi} and Joohon Sung and Spector, {Timothy D} and Sachdev, {Perminder Singh} and Giles, {Graham Gerald} and Southey, {Melissa Caroline} and Hopper, {John L}",
year = "2018",
month = "6",
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pages = "908--916",
journal = "International Journal of Epidemiology",
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Li, S, Wong, EM, Dugué, PA, McRae, A, Kim, E, Joo, JE, Nguyen, TL, Stone, JL, Dite, GS, Armstrong, N, Mather, KA, Thalamuthu, A, Wright, MJ, Ames, DJ, Milne, RL, Craig, JM, Saffery, R, Montgomery, GW, Song, YM, Sung, J, Spector, TD, Sachdev, PS, Giles, GG, Southey, MC & Hopper, JL 2018, 'Genome-wide average DNA methylation is determined in utero' International Journal of Epidemiology, vol. 47, no. 3, pp. 908-916. https://doi.org/10.1093/ije/dyy028

Genome-wide average DNA methylation is determined in utero. / Li, Shuai; Wong, Ee Ming; Dugué, Pierre Antoine; McRae, Allan; Kim, Eunae; Joo, Jihoon Eric; Nguyen, Tuong L.; Stone, Jennifer L; Dite, Gillian S; Armstrong, Nicola; Mather, Karen A; Thalamuthu, Anbupalam; Wright, Margaret J; Ames, David J; Milne, Roger L.; Craig, Jeffrey Mark; Saffery, Richard; Montgomery, Grant W; Song, Yun Mi; Sung, Joohon; Spector, Timothy D; Sachdev, Perminder Singh; Giles, Graham Gerald; Southey, Melissa Caroline; Hopper, John L.

In: International Journal of Epidemiology, Vol. 47, No. 3, 01.06.2018, p. 908-916.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Genome-wide average DNA methylation is determined in utero

AU - Li, Shuai

AU - Wong, Ee Ming

AU - Dugué, Pierre Antoine

AU - McRae, Allan

AU - Kim, Eunae

AU - Joo, Jihoon Eric

AU - Nguyen, Tuong L.

AU - Stone, Jennifer L

AU - Dite, Gillian S

AU - Armstrong, Nicola

AU - Mather, Karen A

AU - Thalamuthu, Anbupalam

AU - Wright, Margaret J

AU - Ames, David J

AU - Milne, Roger L.

AU - Craig, Jeffrey Mark

AU - Saffery, Richard

AU - Montgomery, Grant W

AU - Song, Yun Mi

AU - Sung, Joohon

AU - Spector, Timothy D

AU - Sachdev, Perminder Singh

AU - Giles, Graham Gerald

AU - Southey, Melissa Caroline

AU - Hopper, John L

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Background: Investigating the genetic and environmental causes of variation in genome-wide average DNA methylation (GWAM), a global methylation measure from the HumanMethylation450 array, might give a better understanding of genetic and environmental influences on methylation. Methods: We measured GWAM for 2299 individuals aged 0 to 90 years from seven twin and/or family studies. We estimated familial correlations, modelled correlations with cohabitation history and fitted variance components models for GWAM. Results: The correlation in GWAM for twin pairs was 0.8 at birth, decreased with age during adolescence and was constant at 0.4 throughout adulthood, with no evidence that twin pair correlations differed by zygosity. Non-twin first-degree relatives were correlated, from 0.17 [95% confidence interval (CI): 0.05–0.30] to 0.28 (95% CI: 0.08–0.48), except for middle-aged siblings (0.01, 95% CI: 0.10–0.12), and the correlation increased with time living together and decreased with time living apart. Spouse pairs were correlated in all studies, from 0.23 (95% CI: 0.3–0.43) to 0.31 (95% CI: 0.05–0.52), and the correlation increased with time living together. The variance explained by environmental factors shared by twins alone was 90% (95% CI: 74–95%) at birth, decreased in early life and plateaued at 28% (95% CI: 17–39%) in middle age and beyond. There was a cohabitation-related environmental component of variance. Conclusions: GWAM is determined in utero by prenatal environmental factors, the effects of which persist throughout life. The variation of GWAM is also influenced by environmental factors shared by family members, as well as by individual-specific environmental factors.

AB - Background: Investigating the genetic and environmental causes of variation in genome-wide average DNA methylation (GWAM), a global methylation measure from the HumanMethylation450 array, might give a better understanding of genetic and environmental influences on methylation. Methods: We measured GWAM for 2299 individuals aged 0 to 90 years from seven twin and/or family studies. We estimated familial correlations, modelled correlations with cohabitation history and fitted variance components models for GWAM. Results: The correlation in GWAM for twin pairs was 0.8 at birth, decreased with age during adolescence and was constant at 0.4 throughout adulthood, with no evidence that twin pair correlations differed by zygosity. Non-twin first-degree relatives were correlated, from 0.17 [95% confidence interval (CI): 0.05–0.30] to 0.28 (95% CI: 0.08–0.48), except for middle-aged siblings (0.01, 95% CI: 0.10–0.12), and the correlation increased with time living together and decreased with time living apart. Spouse pairs were correlated in all studies, from 0.23 (95% CI: 0.3–0.43) to 0.31 (95% CI: 0.05–0.52), and the correlation increased with time living together. The variance explained by environmental factors shared by twins alone was 90% (95% CI: 74–95%) at birth, decreased in early life and plateaued at 28% (95% CI: 17–39%) in middle age and beyond. There was a cohabitation-related environmental component of variance. Conclusions: GWAM is determined in utero by prenatal environmental factors, the effects of which persist throughout life. The variation of GWAM is also influenced by environmental factors shared by family members, as well as by individual-specific environmental factors.

KW - DNA methylation

KW - Epigenomics

KW - Twin study

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U2 - 10.1093/ije/dyy028

DO - 10.1093/ije/dyy028

M3 - Article

VL - 47

SP - 908

EP - 916

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

SN - 0300-5771

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ER -