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

Comparison of whole blood DNA methylation in 45 year-old humans with low and high childhood and adulthood socio-economic position 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 45y using MeDIP (methylated DNA immunoprecipitation). We mapped in triplicate the methylation state of promoters of ~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: 9,112 variably methylated probes (from N=223,359 on the microarray) corresponded to 6,176 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. Overall design: 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 45y using MeDIP (methylated DNA immunoprecipitation) with custom-designed microarrays. Probes on the microarrays were selected to tile from -1000bp to +250bp of each transcription start site. Methylation profiles were generated in triplicate.