Genotype effects contribute to variation in longitudinal methylome patterns in older people
Abstract 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 who...
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BMC
2018-10-01
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| Series: | Genome Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s13073-018-0585-7 |
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| author | Qian Zhang Riccardo E Marioni Matthew R Robinson Jon Higham Duncan Sproul Naomi R Wray Ian J Deary Allan F McRae Peter M Visscher |
| author_facet | Qian Zhang Riccardo E Marioni Matthew R Robinson Jon Higham Duncan Sproul Naomi R Wray Ian J Deary Allan F McRae Peter M Visscher |
| author_sort | Qian Zhang |
| collection | DOAJ |
| description | Abstract 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 < 5 × 10−8/1507) SNP effect and 343 rsCpGs had at least one SNP effect (436 SNP-probe pairs) reaching genome-wide significance (P < 5 × 10−8). Ninety-five percent 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. |
| first_indexed | 2024-04-13T16:11:23Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1756-994X |
| language | English |
| last_indexed | 2024-04-13T16:11:23Z |
| publishDate | 2018-10-01 |
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| record_format | Article |
| series | Genome Medicine |
| spelling | doaj.art-ea06486f289a4bf1a79f156881c4cce92022-12-22T02:40:14ZengBMCGenome Medicine1756-994X2018-10-0110111110.1186/s13073-018-0585-7Genotype effects contribute to variation in longitudinal methylome patterns in older peopleQian Zhang0Riccardo E Marioni1Matthew R Robinson2Jon Higham3Duncan Sproul4Naomi R Wray5Ian J Deary6Allan F McRae7Peter M Visscher8Institute for Molecular Bioscience, The University of QueenslandCentre for Cognitive Ageing and Cognitive Epidemiology, University of EdinburghInstitute for Molecular Bioscience, The University of QueenslandMedical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of EdinburghMedical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of EdinburghInstitute for Molecular Bioscience, The University of QueenslandCentre for Cognitive Ageing and Cognitive Epidemiology, University of EdinburghInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandAbstract 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 < 5 × 10−8/1507) SNP effect and 343 rsCpGs had at least one SNP effect (436 SNP-probe pairs) reaching genome-wide significance (P < 5 × 10−8). Ninety-five percent 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.http://link.springer.com/article/10.1186/s13073-018-0585-7DNA methylationLongitudinal analysisMethylation changeG by AGE |
| spellingShingle | Qian Zhang Riccardo E Marioni Matthew R Robinson Jon Higham Duncan Sproul Naomi R Wray Ian J Deary Allan F McRae Peter M Visscher Genotype effects contribute to variation in longitudinal methylome patterns in older people Genome Medicine DNA methylation Longitudinal analysis Methylation change G by AGE |
| title | Genotype effects contribute to variation in longitudinal methylome patterns in older people |
| title_full | Genotype effects contribute to variation in longitudinal methylome patterns in older people |
| title_fullStr | Genotype effects contribute to variation in longitudinal methylome patterns in older people |
| title_full_unstemmed | Genotype effects contribute to variation in longitudinal methylome patterns in older people |
| title_short | Genotype effects contribute to variation in longitudinal methylome patterns in older people |
| title_sort | genotype effects contribute to variation in longitudinal methylome patterns in older people |
| topic | DNA methylation Longitudinal analysis Methylation change G by AGE |
| url | http://link.springer.com/article/10.1186/s13073-018-0585-7 |
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