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Genotype effects contribute to variation in longitudinal methylome patterns in older people

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Original languageEnglish
Pages (from-to)1-11
JournalGenome Medicine
Issue number75
Publication statusPublished - 22 Oct 2018


Background: DNA methylation levels change along with age, but few studies have examined the variation in the rate of such changes between individuals. 
Methods: We performed a longitudinal analysis to quantify the variation in the rate of change of DNA methylation between individuals using whole blood DNA methylation array profiles collected at 2-4 time points (N = 2,894) in 954 individuals (67 - 90 years). 
Results: After stringent quality control, we identified 1,507 DNA methylation CpG sites (rsCpGs) with statistically significant variation in the rate of change (random slope) of DNA methylation among individuals in a mixed linear model analysis. Genes in the vicinity of these rsCpGs were found to be enriched in Homeobox transcription factors and the Wnt signialing pathway, both of which are related to ageing processes. Furthermore, we investigated the SNP effect on the random slope. We found that 4 out of 1,507 rsCpGs had one significant (P < 510-8/1,507) SNP effect and 343 rsCpGs had at least one SNP effect (436 SNP-probe pairs) reaching genome-wide significance (P < 510-8). 95% of the significant (P < 510-8) SNPs are on different chromosomes from their corresponding probes. 
Conclusions: We identified CpG sites that have variability in the rate of change of DNA methylation between individuals, and our results suggest a genetic basis of this variation. Genes around these CpG sites have been reported to be involved in the ageing process.

    Research areas

  • DNA methylation, longitudinal analysis, methylation change, G by AGE

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