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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 were assayed at 713\u2009522 CpG sites from 9537 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, Prickle Planar Cell Polarity Protein 2 and ABI1, Abl-Interactor-1) were annotated to CpG sites associated with preterm birth (P\u2009&amp;lt;\u20091.27\u2009\u00d7\u200910\u22129). A further two genes important to the development of sensory pathways (SOBP, Sine Oculis Binding Protein Homolog and RPGRIP1, Retinitis Pigmentosa GTPase Regulator Interacting Protein) were annotated to sites associated with low birth weight (P\u2009&amp;lt;\u20094.35\u2009\u00d7\u200910\u22128). 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.<\/jats:p>","DOI":"10.1093\/hmg\/ddab274","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T07:11:56Z","timestamp":1631517116000},"page":"651-664","source":"Crossref","is-referenced-by-count":13,"title":["Methylome-wide association study of early life stressors and adult mental health"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6005-1972","authenticated-orcid":false,"given":"David M","family":"Howard","sequence":"first","affiliation":[{"name":"Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK"},{"name":"Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh EH10 5HF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Pain","sequence":"additional","affiliation":[{"name":"Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Arathimos","sequence":"additional","affiliation":[{"name":"Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK"},{"name":"NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London SE5 8AF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miruna C","family":"Barbu","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh EH10 5HF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Amador","sequence":"additional","affiliation":[{"name":"MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosie M","family":"Walker","sequence":"additional","affiliation":[{"name":"Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK"},{"name":"Centre for Clinical Brain Sciences, Chancellor\u2019s Building, 49 Little France Crescent, University of Edinburgh, Edinburgh EH16 4SB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley","family":"Jermy","sequence":"additional","affiliation":[{"name":"Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK"},{"name":"NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London SE5 8AF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J","family":"Adams","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh EH10 5HF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian J","family":"Deary","sequence":"additional","affiliation":[{"name":"Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Porteous","sequence":"additional","affiliation":[{"name":"Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Archie","family":"Campbell","sequence":"additional","affiliation":[{"name":"Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK"},{"name":"Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH16 4UX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick F","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden"},{"name":"Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA"},{"name":"Department of Psychiatry, University of North Carolina, Chapel Hill, NC 27514, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn L","family":"Evans","sequence":"additional","affiliation":[{"name":"Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Arseneault","sequence":"additional","affiliation":[{"name":"Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi R","family":"Wray","sequence":"additional","affiliation":[{"name":"Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Meaney","sequence":"additional","affiliation":[{"name":"Douglas Hospital Research Centre, Douglas Mental Health University Institute, McGill University, Montr\u00e9al, QC H4H 1R3, Canada"},{"name":"Ludmer Centre for Neuroinformatics and Mental Health, McGill University, Montr\u00e9al, QC H3T 1E2, Canada"},{"name":"Singapore Institute for Clinical Sciences, Singapore 117609, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew M","family":"McIntosh","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh EH10 5HF, UK"},{"name":"Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathryn M","family":"Lewis","sequence":"additional","affiliation":[{"name":"Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK"},{"name":"NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London SE5 8AF, 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