Systematic evaluation of DNA methylation age estimation with common preprocessing methods and the Infinium...

Area of Science:

• Epigenetics
• Genomics
• Bioinformatics

Background:

• DNA methylation (DNAm) technologies and bioinformatics methods are rapidly advancing.
• The Illumina EPIC array replaces the 450K array, nearly doubling targeted CpG sites.
• The utility of 450K array tools on EPIC data requires assessment due to missing CpG sites.

Purpose of the Study:

• To assess the utility of DNAm age predictors on the EPIC array.
• To evaluate the impact of data preprocessing on DNAm age estimates.
• To determine if EPIC array data can accurately estimate DNAm age.

Main Methods:

• DNAm quantified on 450K and EPIC platforms from human primary monocytes.
• DNAm age calculated from raw and preprocessed data.
• DNAm age investigated in peripheral blood mononuclear cells, bronchoalveolar lavage, and bronchial brushing samples using the EPIC array.

Main Results:

• DNAm age was highly correlated across platforms and preprocessing methods (r > 0.91).
• Platform and normalization methods introduce systematic offsets in age estimates.
• Median absolute difference in DNAm age between 450K and EPIC was 1.44-3.10 years.

Conclusions:

• Epigenetic clocks are resistant to missing CpG sites on the EPIC array.
• Technical variance is crucial when interpreting group differences in epigenetic data.
• Epigenetic age acceleration is robust across normalization methods and measurement platforms.