Critical evaluation of the reliability of DNA methylation probes on the Illumina MethylationEPIC v1.0 BeadChip microarrays

Figures & data

Figure 1. Distribution of estimated intraclass correlation coefficient (ICC) of DNA methylation levels in EPIC-EPIC comparison, using 69 blood DNA samples, each measured twice, generated by the Alzheimer’s disease neuroimaging initiative study. Dashed lines indicate mode of the distribution.

Figure 2. Probe reliability (ICC) increased as standard deviation (SD) of DNA methylation levels increased.

Figure 3. Higher probe reliability (ICC) is associated with smaller absolute difference in the estimated effect sizes of DNAm-to-AD diagnosis associations in ADNI and AIBL studies (p < 2.2 × 10⁻¹⁶). The effect sizes for DNAm-to-AD associations were obtained from Silva et al. (2022) (PMID: 35982059). Reliability of the probes were determined based on ICC: excellent (>0.75), good (0.6–0.75), fair (0.4–0.6), or poor (<0.4). AD: Alzheimer’s disease.

Figure 4. CpGs probes located within DMRs had higher probe reliability (ICC) compared to other probes in the analysis of (a) Male samples and (b) Female samples (p < 2.2 × 10⁻¹⁶ for both comparisons). The AD-associated DMRs were obtained from table 2 of Silva et al. (2022) (PMID: 36109771).

Data availability statement

The ADNI datasets can be accessed from http://adni.loni.usc.edu. The scripts for the analysis performed in this study are available at https://github.com/TransBioInfoLab/DNAm-reliability