Genotype effects contribute to variation in longitudinal methylome patterns in older people.
Zhang Q., Marioni RE., Robinson MR., Higham J., Sproul D., Wray NR., Deary IJ., McRae AF., Visscher PM.
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 = 2894) in 954 individuals (67-90 years). RESULTS: After stringent quality control, we identified 1507 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 signalling 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 1507 rsCpGs had one significant (P