Methylome-wide association study of early life stressors and adult mental health

David Howard; Ollie Pain; Ryan Arathimos; Miruna C. Barbu; Carmen Amador; Rosie M. Walker; Bradley S. Jermy; Mark Adams; Ian Deary; David J. Porteous; Archie Campbell; Patrick F. Sullivan; Kathryn L Evans; Louise Arseneault; Naomi R. Wray; Michael J. Meaney; Andrew McIntosh; Cathryn Lewis

doi:10.1093/hmg/ddab274

Methylome-wide association study of early life stressors and adult mental health

David Howard, Ollie Pain, Ryan Arathimos, Miruna C. Barbu, Carmen Amador, Rosie M. Walker, Bradley S. Jermy, Mark Adams, Ian Deary, David J. Porteous, Archie Campbell, Patrick F. Sullivan, Kathryn L Evans, Louise Arseneault, Naomi R. Wray, Michael J. Meaney, Andrew McIntosh, Cathryn Lewis

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Abstract

The environment and events that we are exposed to in utero, during birth and in early childhood influence our future physical and mental health. The underlying mechanisms that lead to these outcomes are unclear, but long-term changes in epigenetic marks, such as DNA methylation, could act as a mediating factor or biomarker. DNA methylation data was assayed at 713,522 CpG sites from 9,537 participants of the Generation Scotland: Scottish Family Health Study, a family-based cohort with extensive genetic, medical, family history and lifestyle information. Methylome-wide association studies of eight early life environment phenotypes and two adult mental health phenotypes (major depressive disorder and brief resilience scale) were conducted using DNA methylation data collected from adult whole blood samples. Two genes involved with different developmental pathways (PRICKLE2 and ABI1) were annotated to CpG sites associated with preterm birth (P < 1.27×10^-9). A further two genes important to the development of sensory pathways (SOBP and RPGRIP1) were annotated to sites associated with low birth weight (P < 4.35×10^-8). The examination of methylation profile scores and genes and gene-sets annotated from associated CpGs sites found no evidence of overlap between the early life environment and mental health conditions. Birth date was associated with a significant difference in estimated lymphocyte and neutrophil counts. Previous studies have shown that early life environments influence the risk of developing mental health disorders later in life; however, this study found no evidence that this is mediated by stable changes to the methylome detectable in peripheral blood.

Original language	English
Pages (from-to)	651–664
Journal	Human Molecular Genetics
Volume	31
Issue number	4
DOIs	https://doi.org/10.1093/hmg/ddab274
Publication status	Published - 15 Sept 2021

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Methylome-wide association study of early life stressors and adult mental healthAccepted author manuscript, 973 KBLicence: CC BY

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Howard, D., Pain, O., Arathimos, R., Barbu, M. C., Amador, C., Walker, R. M., Jermy, B. S., Adams, M., Deary, I., Porteous, D. J., Campbell, A., Sullivan, P. F., Evans, K. L., Arseneault, L., Wray, N. R., Meaney, M. J., McIntosh, A., & Lewis, C. (2021). Methylome-wide association study of early life stressors and adult mental health. Human Molecular Genetics, 31(4), 651–664. https://doi.org/10.1093/hmg/ddab274

@article{27292c09179b4666804056c452707316,

title = "Methylome-wide association study of early life stressors and adult mental health",

abstract = "The environment and events that we are exposed to in utero, during birth and in early childhood influence our future physical and mental health. The underlying mechanisms that lead to these outcomes are unclear, but long-term changes in epigenetic marks, such as DNA methylation, could act as a mediating factor or biomarker. DNA methylation data was assayed at 713,522 CpG sites from 9,537 participants of the Generation Scotland: Scottish Family Health Study, a family-based cohort with extensive genetic, medical, family history and lifestyle information. Methylome-wide association studies of eight early life environment phenotypes and two adult mental health phenotypes (major depressive disorder and brief resilience scale) were conducted using DNA methylation data collected from adult whole blood samples. Two genes involved with different developmental pathways (PRICKLE2 and ABI1) were annotated to CpG sites associated with preterm birth (P < 1.27×10-9). A further two genes important to the development of sensory pathways (SOBP and RPGRIP1) were annotated to sites associated with low birth weight (P < 4.35×10-8). The examination of methylation profile scores and genes and gene-sets annotated from associated CpGs sites found no evidence of overlap between the early life environment and mental health conditions. Birth date was associated with a significant difference in estimated lymphocyte and neutrophil counts. Previous studies have shown that early life environments influence the risk of developing mental health disorders later in life; however, this study found no evidence that this is mediated by stable changes to the methylome detectable in peripheral blood.",

author = "David Howard and Ollie Pain and Ryan Arathimos and Barbu, {Miruna C.} and Carmen Amador and Walker, {Rosie M.} and Jermy, {Bradley S.} and Mark Adams and Ian Deary and Porteous, {David J.} and Archie Campbell and Sullivan, {Patrick F.} and Evans, {Kathryn L} and Louise Arseneault and Wray, {Naomi R.} and Meaney, {Michael J.} and Andrew McIntosh and Cathryn Lewis",

year = "2021",

month = sep,

day = "15",

doi = "10.1093/hmg/ddab274",

language = "English",

volume = "31",

pages = "651–664",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

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Howard, D , Pain, O , Arathimos, R, Barbu, MC, Amador, C, Walker, RM, Jermy, BS, Adams, M, Deary, I, Porteous, DJ, Campbell, A, Sullivan, PF, Evans, KL, Arseneault, L, Wray, NR, Meaney, MJ, McIntosh, A & Lewis, C 2021, 'Methylome-wide association study of early life stressors and adult mental health', Human Molecular Genetics, vol. 31, no. 4, pp. 651–664. https://doi.org/10.1093/hmg/ddab274

TY - JOUR

T1 - Methylome-wide association study of early life stressors and adult mental health

AU - Howard, David

AU - Pain, Ollie

AU - Arathimos, Ryan

AU - Barbu, Miruna C.

AU - Amador, Carmen

AU - Walker, Rosie M.

AU - Jermy, Bradley S.

AU - Adams, Mark

AU - Deary, Ian

AU - Porteous, David J.

AU - Campbell, Archie

AU - Sullivan, Patrick F.

AU - Evans, Kathryn L

AU - Arseneault, Louise

AU - Wray, Naomi R.

AU - Meaney, Michael J.

AU - McIntosh, Andrew

AU - Lewis, Cathryn

PY - 2021/9/15

Y1 - 2021/9/15

N2 - The environment and events that we are exposed to in utero, during birth and in early childhood influence our future physical and mental health. The underlying mechanisms that lead to these outcomes are unclear, but long-term changes in epigenetic marks, such as DNA methylation, could act as a mediating factor or biomarker. DNA methylation data was assayed at 713,522 CpG sites from 9,537 participants of the Generation Scotland: Scottish Family Health Study, a family-based cohort with extensive genetic, medical, family history and lifestyle information. Methylome-wide association studies of eight early life environment phenotypes and two adult mental health phenotypes (major depressive disorder and brief resilience scale) were conducted using DNA methylation data collected from adult whole blood samples. Two genes involved with different developmental pathways (PRICKLE2 and ABI1) were annotated to CpG sites associated with preterm birth (P < 1.27×10-9). A further two genes important to the development of sensory pathways (SOBP and RPGRIP1) were annotated to sites associated with low birth weight (P < 4.35×10-8). The examination of methylation profile scores and genes and gene-sets annotated from associated CpGs sites found no evidence of overlap between the early life environment and mental health conditions. Birth date was associated with a significant difference in estimated lymphocyte and neutrophil counts. Previous studies have shown that early life environments influence the risk of developing mental health disorders later in life; however, this study found no evidence that this is mediated by stable changes to the methylome detectable in peripheral blood.

AB - The environment and events that we are exposed to in utero, during birth and in early childhood influence our future physical and mental health. The underlying mechanisms that lead to these outcomes are unclear, but long-term changes in epigenetic marks, such as DNA methylation, could act as a mediating factor or biomarker. DNA methylation data was assayed at 713,522 CpG sites from 9,537 participants of the Generation Scotland: Scottish Family Health Study, a family-based cohort with extensive genetic, medical, family history and lifestyle information. Methylome-wide association studies of eight early life environment phenotypes and two adult mental health phenotypes (major depressive disorder and brief resilience scale) were conducted using DNA methylation data collected from adult whole blood samples. Two genes involved with different developmental pathways (PRICKLE2 and ABI1) were annotated to CpG sites associated with preterm birth (P < 1.27×10-9). A further two genes important to the development of sensory pathways (SOBP and RPGRIP1) were annotated to sites associated with low birth weight (P < 4.35×10-8). The examination of methylation profile scores and genes and gene-sets annotated from associated CpGs sites found no evidence of overlap between the early life environment and mental health conditions. Birth date was associated with a significant difference in estimated lymphocyte and neutrophil counts. Previous studies have shown that early life environments influence the risk of developing mental health disorders later in life; however, this study found no evidence that this is mediated by stable changes to the methylome detectable in peripheral blood.

U2 - 10.1093/hmg/ddab274

DO - 10.1093/hmg/ddab274

M3 - Article

SN - 0964-6906

VL - 31

SP - 651

EP - 664

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 4

ER -

Methylome-wide association study of early life stressors and adult mental health

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