Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age

Ken W K Lee; Rebecca Richmond; Pingzhao Hu; Leon French; Jean Shin; Celine Bourdon; Eva Reischl; Melanie Waldenberger; Sonja Zeilinger; Tom Gaunt; Wendy McArdle; Susan Ring; Geoff Woodward; Luigi Bouchard; Daniel Gaudet; George Davey Smith; Caroline Relton; Tomas Paus; Zdenka Pausova

doi:10.1289/ehp.1408614

Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age

Ken W K Lee, Rebecca Richmond, Pingzhao Hu, Leon French, Jean Shin, Celine Bourdon, Eva Reischl, Melanie Waldenberger, Sonja Zeilinger, Tom Gaunt, Wendy McArdle, Susan Ring, Geoff Woodward, Luigi Bouchard, Daniel Gaudet, George Davey Smith, Caroline Relton, Tomas Paus, Zdenka Pausova^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

159 Citations (Scopus)

Abstract

BACKGROUND: Prenatal exposure to maternal cigarette smoking (prenatal smoke exposure) had been associated with altered DNA methylation (DNAm) at birth.

OBJECTIVE: We examined whether such alterations are present from birth through adolescence.

METHODS: We used the Infinium HumanMethylation450K BeadChip to search across 473,395 CpGs for differential DNAm associated with prenatal smoke exposure during adolescence in a discovery cohort (n = 132) and at birth, during childhood, and during adolescence in a replication cohort (n = 447).

RESULTS: In the discovery cohort, we found five CpGs in MYO1G (top-ranking CpG: cg12803068, p = 3.3 × 10-11) and CNTNAP2 (cg25949550, p = 4.0 × 10-9) to be differentially methylated between exposed and nonexposed individuals during adolescence. The CpGs in MYO1G and CNTNAP2 were associated, respectively, with higher and lower DNAm in exposed versus nonexposed adolescents. The same CpGs were differentially methylated at birth, during childhood, and during adolescence in the replication cohort. In both cohorts and at all developmental time points, the differential DNAm was in the same direction and of a similar magnitude, and was not altered appreciably by adjustment for current smoking by the participants or their parents. In addition, four of the five EWAS (epigenome-wide association study)-significant CpGs in the adolescent discovery cohort were also among the top sites of differential methylation in a previous birth cohort, and differential methylation of CpGs in CYP1A1, AHRR, and GFI1 observed in that study was also evident in our discovery cohort.

CONCLUSIONS: Our findings suggest that modifications of DNAm associated with prenatal maternal smoking may persist in exposed offspring for many years-at least until adolescence.

Original language	English
Pages (from-to)	193-199
Number of pages	7
Journal	Environmental Health Perspectives
Volume	123
Issue number	2
DOIs	https://doi.org/10.1289/ehp.1408614
Publication status	Published - 1 Jan 2015

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The biosocial archive: transforming lifecourse social research through the incorporation of epigenetic measures
Davey Smith, G. (Principal Investigator)
1/10/13 → 1/04/15
Project: Research
IEU Theme 2
Flach, P. A. (Principal Investigator), Gaunt, T. R. (Principal Investigator) & Gaunt, T. R. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
MRC UoB UNITE Unit - programme 3
Timpson, N. J. (Principal Investigator) & Timpson, N. J. (Principal Investigator)
1/06/13 → 31/03/18
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Illumina Array
Ring, S. M. (Manager)
Bristol Population Health Science Institute
Facility/equipment: Facility

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Lee, K. W. K., Richmond, R., Hu, P., French, L., Shin, J., Bourdon, C., Reischl, E., Waldenberger, M., Zeilinger, S., Gaunt, T., McArdle, W., Ring, S., Woodward, G., Bouchard, L., Gaudet, D., Smith, G. D., Relton, C., Paus, T., & Pausova, Z. (2015). Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age. Environmental Health Perspectives, 123(2), 193-199. https://doi.org/10.1289/ehp.1408614

@article{06c696502f13409ca3ef340e7d4b60eb,

title = "Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age",

abstract = "BACKGROUND: Prenatal exposure to maternal cigarette smoking (prenatal smoke exposure) had been associated with altered DNA methylation (DNAm) at birth.OBJECTIVE: We examined whether such alterations are present from birth through adolescence.METHODS: We used the Infinium HumanMethylation450K BeadChip to search across 473,395 CpGs for differential DNAm associated with prenatal smoke exposure during adolescence in a discovery cohort (n = 132) and at birth, during childhood, and during adolescence in a replication cohort (n = 447).RESULTS: In the discovery cohort, we found five CpGs in MYO1G (top-ranking CpG: cg12803068, p = 3.3 × 10-11) and CNTNAP2 (cg25949550, p = 4.0 × 10-9) to be differentially methylated between exposed and nonexposed individuals during adolescence. The CpGs in MYO1G and CNTNAP2 were associated, respectively, with higher and lower DNAm in exposed versus nonexposed adolescents. The same CpGs were differentially methylated at birth, during childhood, and during adolescence in the replication cohort. In both cohorts and at all developmental time points, the differential DNAm was in the same direction and of a similar magnitude, and was not altered appreciably by adjustment for current smoking by the participants or their parents. In addition, four of the five EWAS (epigenome-wide association study)-significant CpGs in the adolescent discovery cohort were also among the top sites of differential methylation in a previous birth cohort, and differential methylation of CpGs in CYP1A1, AHRR, and GFI1 observed in that study was also evident in our discovery cohort.CONCLUSIONS: Our findings suggest that modifications of DNAm associated with prenatal maternal smoking may persist in exposed offspring for many years-at least until adolescence.",

author = "Lee, {Ken W K} and Rebecca Richmond and Pingzhao Hu and Leon French and Jean Shin and Celine Bourdon and Eva Reischl and Melanie Waldenberger and Sonja Zeilinger and Tom Gaunt and Wendy McArdle and Susan Ring and Geoff Woodward and Luigi Bouchard and Daniel Gaudet and Smith, {George Davey} and Caroline Relton and Tomas Paus and Zdenka Pausova",

year = "2015",

month = jan,

day = "1",

doi = "10.1289/ehp.1408614",

language = "English",

volume = "123",

pages = "193--199",

journal = "Environmental Health Perspectives",

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publisher = "Public Health Services, US Dept of Health and Human Services",

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Lee, KWK, Richmond, R, Hu, P, French, L, Shin, J, Bourdon, C, Reischl, E, Waldenberger, M, Zeilinger, S, Gaunt, T, McArdle, W, Ring, S, Woodward, G, Bouchard, L, Gaudet, D, Smith, GD, Relton, C, Paus, T & Pausova, Z 2015, 'Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age', Environmental Health Perspectives, vol. 123, no. 2, pp. 193-199. https://doi.org/10.1289/ehp.1408614

Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age. / Lee, Ken W K; Richmond, Rebecca; Hu, Pingzhao et al.
In: Environmental Health Perspectives, Vol. 123, No. 2, 01.01.2015, p. 193-199.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Prenatal exposure to maternal cigarette smoking and DNA methylation

T2 - epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age

AU - Lee, Ken W K

AU - Richmond, Rebecca

AU - Hu, Pingzhao

AU - French, Leon

AU - Shin, Jean

AU - Bourdon, Celine

AU - Reischl, Eva

AU - Waldenberger, Melanie

AU - Zeilinger, Sonja

AU - Gaunt, Tom

AU - McArdle, Wendy

AU - Ring, Susan

AU - Woodward, Geoff

AU - Bouchard, Luigi

AU - Gaudet, Daniel

AU - Smith, George Davey

AU - Relton, Caroline

AU - Paus, Tomas

AU - Pausova, Zdenka

PY - 2015/1/1

Y1 - 2015/1/1

N2 - BACKGROUND: Prenatal exposure to maternal cigarette smoking (prenatal smoke exposure) had been associated with altered DNA methylation (DNAm) at birth.OBJECTIVE: We examined whether such alterations are present from birth through adolescence.METHODS: We used the Infinium HumanMethylation450K BeadChip to search across 473,395 CpGs for differential DNAm associated with prenatal smoke exposure during adolescence in a discovery cohort (n = 132) and at birth, during childhood, and during adolescence in a replication cohort (n = 447).RESULTS: In the discovery cohort, we found five CpGs in MYO1G (top-ranking CpG: cg12803068, p = 3.3 × 10-11) and CNTNAP2 (cg25949550, p = 4.0 × 10-9) to be differentially methylated between exposed and nonexposed individuals during adolescence. The CpGs in MYO1G and CNTNAP2 were associated, respectively, with higher and lower DNAm in exposed versus nonexposed adolescents. The same CpGs were differentially methylated at birth, during childhood, and during adolescence in the replication cohort. In both cohorts and at all developmental time points, the differential DNAm was in the same direction and of a similar magnitude, and was not altered appreciably by adjustment for current smoking by the participants or their parents. In addition, four of the five EWAS (epigenome-wide association study)-significant CpGs in the adolescent discovery cohort were also among the top sites of differential methylation in a previous birth cohort, and differential methylation of CpGs in CYP1A1, AHRR, and GFI1 observed in that study was also evident in our discovery cohort.CONCLUSIONS: Our findings suggest that modifications of DNAm associated with prenatal maternal smoking may persist in exposed offspring for many years-at least until adolescence.

AB - BACKGROUND: Prenatal exposure to maternal cigarette smoking (prenatal smoke exposure) had been associated with altered DNA methylation (DNAm) at birth.OBJECTIVE: We examined whether such alterations are present from birth through adolescence.METHODS: We used the Infinium HumanMethylation450K BeadChip to search across 473,395 CpGs for differential DNAm associated with prenatal smoke exposure during adolescence in a discovery cohort (n = 132) and at birth, during childhood, and during adolescence in a replication cohort (n = 447).RESULTS: In the discovery cohort, we found five CpGs in MYO1G (top-ranking CpG: cg12803068, p = 3.3 × 10-11) and CNTNAP2 (cg25949550, p = 4.0 × 10-9) to be differentially methylated between exposed and nonexposed individuals during adolescence. The CpGs in MYO1G and CNTNAP2 were associated, respectively, with higher and lower DNAm in exposed versus nonexposed adolescents. The same CpGs were differentially methylated at birth, during childhood, and during adolescence in the replication cohort. In both cohorts and at all developmental time points, the differential DNAm was in the same direction and of a similar magnitude, and was not altered appreciably by adjustment for current smoking by the participants or their parents. In addition, four of the five EWAS (epigenome-wide association study)-significant CpGs in the adolescent discovery cohort were also among the top sites of differential methylation in a previous birth cohort, and differential methylation of CpGs in CYP1A1, AHRR, and GFI1 observed in that study was also evident in our discovery cohort.CONCLUSIONS: Our findings suggest that modifications of DNAm associated with prenatal maternal smoking may persist in exposed offspring for many years-at least until adolescence.

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U2 - 10.1289/ehp.1408614

DO - 10.1289/ehp.1408614

M3 - Article (Academic Journal)

C2 - 25325234

AN - SCOPUS:84923036855

SN - 0091-6765

VL - 123

SP - 193

EP - 199

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

IS - 2

ER -

Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age

Abstract

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Projects

The biosocial archive: transforming lifecourse social research through the incorporation of epigenetic measures

IEU Theme 2

MRC UoB UNITE Unit - programme 3

Equipment

Illumina Array

Cite this