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Evaluating DNA methylation age on the Illumina MethylationEPIC Bead Chip.

Publication ,  Journal Article
Dhingra, R; Kwee, LC; Diaz-Sanchez, D; Devlin, RB; Cascio, W; Hauser, ER; Gregory, S; Shah, S; Kraus, WE; Olden, K; Ward-Caviness, CK
Published in: PLoS One
2019

DNA methylation age (DNAm age) has become a widely utilized epigenetic biomarker for the aging process. The Horvath method for determining DNAm age is perhaps the most widely utilized and validated DNA methylation age assessment measure. Horvath DNAm age is calculated based on methylation measurements at 353 loci, present on Illumina's 450k and 27k DNA methylation microarrays. With increasing use of the more recently developed Illumina MethylationEPIC (850k) microarray, it is worth revisiting this aging measure to evaluate estimation differences due to array design. Of the requisite 353 loci, 17 are missing from the 850k microarray. Similarly, an alternate, 71 loci DNA methylation age assessment measure created by Hannum et al. is missing 6 requisite loci. Using 17 datasets with 27k, 450k, and/or 850k methylation data, we compared each sample's epigenetic age estimated from all 353 loci required by the Horvath DNAm age calculator, and using only the 336 loci available on the 850k array. In 450k/27k data, removing loci not on the 850k array resulted in underestimation of Horvath's DNAm age. Underestimation of Horvath DNAm age increased from ages 0 to ~20, remaining stable thereafter (mean deviation = -3.46 y, SD = 1.13 for individuals ≥20 years). Underestimation of Horvath's DNAm age by the reduced 450k/27k data was similar to the underestimation observed in the 850k data indicating it is driven by missing probes. In analogous examination of Hannum's DNAm age, the magnitude and direction of epigenetic age misestimation varied with chronological age. In conclusion, inter-array deviations in DNAm age estimations may be largely driven by missing probes between arrays, despite default probe imputation procedures. Though correlations and associations based on Horvath's DNAm age may be unaffected, researchers should exercise caution when interpreting results based on absolute differences in DNAm age or when mixing samples assayed on different arrays.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2019

Volume

14

Issue

4

Start / End Page

e0207834

Location

United States

Related Subject Headings

  • Young Adult
  • Polymorphism, Single Nucleotide
  • Oligonucleotide Array Sequence Analysis
  • Middle Aged
  • Male
  • Infant
  • Humans
  • Genetic Loci
  • General Science & Technology
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
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Dhingra, R., Kwee, L. C., Diaz-Sanchez, D., Devlin, R. B., Cascio, W., Hauser, E. R., … Ward-Caviness, C. K. (2019). Evaluating DNA methylation age on the Illumina MethylationEPIC Bead Chip. PLoS One, 14(4), e0207834. https://doi.org/10.1371/journal.pone.0207834
Dhingra, Radhika, Lydia Coulter Kwee, David Diaz-Sanchez, Robert B. Devlin, Wayne Cascio, Elizabeth R. Hauser, Simon Gregory, et al. “Evaluating DNA methylation age on the Illumina MethylationEPIC Bead Chip.PLoS One 14, no. 4 (2019): e0207834. https://doi.org/10.1371/journal.pone.0207834.
Dhingra R, Kwee LC, Diaz-Sanchez D, Devlin RB, Cascio W, Hauser ER, et al. Evaluating DNA methylation age on the Illumina MethylationEPIC Bead Chip. PLoS One. 2019;14(4):e0207834.
Dhingra, Radhika, et al. “Evaluating DNA methylation age on the Illumina MethylationEPIC Bead Chip.PLoS One, vol. 14, no. 4, 2019, p. e0207834. Pubmed, doi:10.1371/journal.pone.0207834.
Dhingra R, Kwee LC, Diaz-Sanchez D, Devlin RB, Cascio W, Hauser ER, Gregory S, Shah S, Kraus WE, Olden K, Ward-Caviness CK. Evaluating DNA methylation age on the Illumina MethylationEPIC Bead Chip. PLoS One. 2019;14(4):e0207834.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2019

Volume

14

Issue

4

Start / End Page

e0207834

Location

United States

Related Subject Headings

  • Young Adult
  • Polymorphism, Single Nucleotide
  • Oligonucleotide Array Sequence Analysis
  • Middle Aged
  • Male
  • Infant
  • Humans
  • Genetic Loci
  • General Science & Technology
  • Female