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Characterizing the human methylome across the life course: findings from eight UK-based studies

View ORCID ProfileEsther Walton, Riccardo Marioni, Hannah R Elliott, Simon R Cox, Ian J Deary, View ORCID ProfileAlun D Hughes, Therese Tillin, Meena Kumari, Tom Woofenden, Juan E Castillo-Fernandez, Jordana T Bell, Alissa Goodman, George Ploubidis, Kate Tilling, Matthew Suderman, Tom R Gaunt, Erin C Dunn, Andrew Smith, Caroline L Relton
doi: https://doi.org/10.1101/2021.09.18.460916
Esther Walton
1Department of Psychology, University of Bath, Bath, United Kingdom
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  • For correspondence: E.Walton@bath.ac.uk
Riccardo Marioni
2Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom
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Hannah R Elliott
3MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
4Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
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Simon R Cox
5The Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, United Kingdom
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Ian J Deary
5The Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, United Kingdom
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Alun D Hughes
6MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, University College London, London, United Kingdom
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Therese Tillin
6MRC Unit for Lifelong Health and Ageing at UCL, Institute of Cardiovascular Science, University College London, London, United Kingdom
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Meena Kumari
7Institution of Social and Economic Research, University of Essex, Colchester, United Kingdom
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Tom Woofenden
1Department of Psychology, University of Bath, Bath, United Kingdom
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Juan E Castillo-Fernandez
8Department of Twin Research and Genetic Epidemiology, King’s College London, UK
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Jordana T Bell
8Department of Twin Research and Genetic Epidemiology, King’s College London, UK
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Alissa Goodman
9Centre for Longitudinal Studies, UCL Social Research Institute, University College London, London, UK
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George Ploubidis
9Centre for Longitudinal Studies, UCL Social Research Institute, University College London, London, UK
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Kate Tilling
3MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
4Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
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Matthew Suderman
3MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
4Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
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Tom R Gaunt
3MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
4Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
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Erin C Dunn
10Department of Psychiatry and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States
11Department of Psychiatry, Harvard Medical School, Boston, MA, United States
12Center on the Developing Child at Harvard University, Cambridge, MA, United States
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Andrew Smith
13Mathematics and Statistics Research Group, University of the West of England, Bristol, United Kingdom
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Caroline L Relton
3MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
4Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
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Abstract

Variation in DNA methylation (DNAm) is associated with multiple biological processes that track growth and development, ageing and age-related diseases. However, there is little understanding of what constitutes typical patterns of DNAm variation and how these patterns change across the life course. In this study, we synthesised a map of the human methylome across the life course, focussing on changes in variability and mean DNAm.

Harmonizing DNAm datasets across eight longitudinal and cross-sectional UK-based studies, we meta-analysed n=13,215 blood samples from n=7,037 unique individuals from birth to 98 years of age. Changes in CpG-specific variability and means were described across the life course using a meta-regression framework. CpG-specific associations of variability or mean DNAm in relation to the likelihood of association with 100 traits linked to environmental exposures, health and disease were tested within and across ten developmental age bins across the life course.

Age was linked to DNAm variability at 29,212 CpG sites. On average, we observed a 1.26 fold increase in DNAm variability per year across the life course. 33,730 CpGs displayed changes in mean DNAm, with 64% of these loci showing decreases in DNAm over time. CpG sites linked to traits were in general more variable across the life course.

Our study provides, for the first time, a map of the human methylome across the life course, which is publicly accessible through a searchable online database. This resource allows researchers to query CpG-specific trajectories from birth to old age and link these to health and disease.

Competing Interest Statement

REM has received payment from Illumina for a presentation. TRG receives research funding from Biogen for unrelated research.

Footnotes

  • ↵* shared authorship

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Characterizing the human methylome across the life course: findings from eight UK-based studies
Esther Walton, Riccardo Marioni, Hannah R Elliott, Simon R Cox, Ian J Deary, Alun D Hughes, Therese Tillin, Meena Kumari, Tom Woofenden, Juan E Castillo-Fernandez, Jordana T Bell, Alissa Goodman, George Ploubidis, Kate Tilling, Matthew Suderman, Tom R Gaunt, Erin C Dunn, Andrew Smith, Caroline L Relton
bioRxiv 2021.09.18.460916; doi: https://doi.org/10.1101/2021.09.18.460916
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Characterizing the human methylome across the life course: findings from eight UK-based studies
Esther Walton, Riccardo Marioni, Hannah R Elliott, Simon R Cox, Ian J Deary, Alun D Hughes, Therese Tillin, Meena Kumari, Tom Woofenden, Juan E Castillo-Fernandez, Jordana T Bell, Alissa Goodman, George Ploubidis, Kate Tilling, Matthew Suderman, Tom R Gaunt, Erin C Dunn, Andrew Smith, Caroline L Relton
bioRxiv 2021.09.18.460916; doi: https://doi.org/10.1101/2021.09.18.460916

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