Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time
Epigenome-wide association studies (EWAS) have focused primarily on DNA methylation as a chemically stable and functional epigenetic modification. However, the stability and accuracy of the measurement of methylation in different tissues and extraction types is still being actively studied, and the...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-01-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2017.1411443 |
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| author | Marie Forest Kieran J. O'Donnell Greg Voisin Helene Gaudreau Julia L. MacIsaac Lisa M. McEwen Patricia P. Silveira Meir Steiner Michael S. Kobor Michael J. Meaney Celia M.T. Greenwood |
| author_facet | Marie Forest Kieran J. O'Donnell Greg Voisin Helene Gaudreau Julia L. MacIsaac Lisa M. McEwen Patricia P. Silveira Meir Steiner Michael S. Kobor Michael J. Meaney Celia M.T. Greenwood |
| author_sort | Marie Forest |
| collection | DOAJ |
| description | Epigenome-wide association studies (EWAS) have focused primarily on DNA methylation as a chemically stable and functional epigenetic modification. However, the stability and accuracy of the measurement of methylation in different tissues and extraction types is still being actively studied, and the longitudinal stability of DNA methylation in commonly studied peripheral tissues is of great interest. Here, we used data from two studies, three tissue types, and multiple time points to assess the stability of DNA methylation measured with the Illumina Infinium HumanMethylation450 BeadChip array. Redundancy analysis enabled visual assessment of agreement of replicate samples overall and showed good agreement after removing effects of tissue type, age, and sex. At the probe level, analysis of variance contrasts separating technical and biological replicates clearly showed better agreement between technical replicates versus longitudinal samples, and suggested increased stability for buccal cells versus blood or blood spots. Intraclass correlations (ICCs) demonstrated that inter-individual variability is of similar magnitude to within-sample variability at many probes; however, as inter-individual variability increased, so did ICC. Furthermore, we were able to demonstrate decreasing agreement in methylation levels with time, despite a maximal sampling interval of only 576 days. Finally, at 6 popular candidate genes, there was a large range of stability across probes. Our findings highlight important sources of technical and biological variation in DNA methylation across different tissues over time. These data will help to inform longitudinal sampling strategies of future EWAS. |
| first_indexed | 2024-03-11T23:07:16Z |
| format | Article |
| id | doaj.art-38e7a687521c4744bb54c7d66f98b099 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:07:16Z |
| publishDate | 2018-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-38e7a687521c4744bb54c7d66f98b0992023-09-21T13:09:20ZengTaylor & Francis GroupEpigenetics1559-22941559-23082018-01-01131193210.1080/15592294.2017.14114431411443Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and timeMarie Forest0Kieran J. O'Donnell1Greg Voisin2Helene Gaudreau3Julia L. MacIsaac4Lisa M. McEwen5Patricia P. Silveira6Meir Steiner7Michael S. Kobor8Michael J. Meaney9Celia M.T. Greenwood10Lady Davis InstituteMcGill UniversityLady Davis InstituteMcGill Universityand BC Children's Hospital Research Institute, University of British Columbiaand BC Children's Hospital Research Institute, University of British ColumbiaMcGill UniversityMcMaster Universityand BC Children's Hospital Research Institute, University of British ColumbiaMcGill UniversityLady Davis InstituteEpigenome-wide association studies (EWAS) have focused primarily on DNA methylation as a chemically stable and functional epigenetic modification. However, the stability and accuracy of the measurement of methylation in different tissues and extraction types is still being actively studied, and the longitudinal stability of DNA methylation in commonly studied peripheral tissues is of great interest. Here, we used data from two studies, three tissue types, and multiple time points to assess the stability of DNA methylation measured with the Illumina Infinium HumanMethylation450 BeadChip array. Redundancy analysis enabled visual assessment of agreement of replicate samples overall and showed good agreement after removing effects of tissue type, age, and sex. At the probe level, analysis of variance contrasts separating technical and biological replicates clearly showed better agreement between technical replicates versus longitudinal samples, and suggested increased stability for buccal cells versus blood or blood spots. Intraclass correlations (ICCs) demonstrated that inter-individual variability is of similar magnitude to within-sample variability at many probes; however, as inter-individual variability increased, so did ICC. Furthermore, we were able to demonstrate decreasing agreement in methylation levels with time, despite a maximal sampling interval of only 576 days. Finally, at 6 popular candidate genes, there was a large range of stability across probes. Our findings highlight important sources of technical and biological variation in DNA methylation across different tissues over time. These data will help to inform longitudinal sampling strategies of future EWAS.http://dx.doi.org/10.1080/15592294.2017.1411443intraclass correlationsmethylationredundancy analysisreplicationtissue stability |
| spellingShingle | Marie Forest Kieran J. O'Donnell Greg Voisin Helene Gaudreau Julia L. MacIsaac Lisa M. McEwen Patricia P. Silveira Meir Steiner Michael S. Kobor Michael J. Meaney Celia M.T. Greenwood Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time Epigenetics intraclass correlations methylation redundancy analysis replication tissue stability |
| title | Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time |
| title_full | Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time |
| title_fullStr | Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time |
| title_full_unstemmed | Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time |
| title_short | Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time |
| title_sort | agreement in dna methylation levels from the illumina 450k array across batches tissues and time |
| topic | intraclass correlations methylation redundancy analysis replication tissue stability |
| url | http://dx.doi.org/10.1080/15592294.2017.1411443 |
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