Associations with early-life socio-economic position in adult DNA methylation

Associations with early-life socio-economic position in adult DNA methylationNada Borghol1,2,†, Matthew Suderman1,2,3,†, Wendy McArdle4, Ariane Racine1,2, Michael Hallett3, Marcus Pembrey5,*, Clyde Hertzman6,*, Chris Power7,* and Moshe Szyf1,2,*

+ Author Affiliations
1Sackler Program for Epigenetics & Developmental Psychobiology, McGill University, Montreal, Quebec, Canada, 2Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada, 3McGill Centre for Bioinformatics, McGill University, Montreal, Quebec, Canada, 4Department of Social Medicine, University of Bristol, Bristol, UK, 5Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, UK, 6Human Early Learning Partnership, University of British Columbia, Vancouver, British Columbia, Canada and 7MRC Centre of Epidemiology for Child Health, Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK
*Corresponding authors. Moshe Szyf, Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade #1309, Montreal, Quebec, Canada H3G 1Y6. E-mail: moshe.szyf@mcgill.ca; Chris Power, MRC Centre of Epidemiology for Child Health, Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK. E-mail: c.power@ich.ucl.ac.uk; Clyde Hertzman, Human Early Learning Partnership, University of British Columbia, 440 - 2206 East Mall, Vancouver, Canada BC V6T 1Z3. E-mail: clyde.hertzman@ubc.ca; Marcus Pembrey, Clinical and Molecular Genetics Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK. E-mail: m.pembrey@bristol.ac.uk
Accepted August 25, 2011.
Abstract
Background
Disadvantaged socio-economic position (SEP) in childhood is associated with increased adult mortality and morbidity. We aimed to establish whether childhood SEP was associated with differential methylation of adult DNA.
Methods
Forty adult males from the 1958 British Birth Cohort Study were selected from SEP extremes in both early childhood and mid-adulthood. We performed genome-wide methylation analysis on blood DNA taken at 45 years using MeDIP (methylated DNA immunoprecipitation). We mapped in triplicate the methylation state of promoters of approximately 20 000 genes and 400 microRNAs. Probe methylation scores were averaged across triplicates and differential methylation between groups of individuals was determined. Differentially methylated promoter sites of selected genes were validated using pyrosequencing of bisulfite-converted DNA.
Results
Variably methylated probes (9112 from n = 223 359 on the microarray) corresponded to 6176 gene promoters with at least one variable probe. Unsupervised hierarchical clustering of probes obtained from the 500 most variable promoters revealed a cluster enriched with high SEP individuals confirming that SEP differences contribute to overall epigenetic variation. Methylation levels for 1252 gene promoters were associated with childhood SEP vs 545 promoters for adulthood SEP. Functionally, associations with childhood SEP appear in promoters of genes enriched in key cell signalling pathways. The differentially methylated promoters associated with SEP cluster in megabase-sized regions of the genome.
Conclusions
Adult blood DNA methylation profiles show more associations with childhood SEP than adult SEP. Organization of these associations across the genome suggests a well-defined epigenetic pattern linked to early socio-economic environment.
Key words
1958 British birth cohortadult DNA methylation profilechildhood socio-economic position

Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2011; all rights reserved.
Associations with early-life socio-economic position in adult DNA methylation