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Creating and Validating a DNA Methylation-Based Proxy for Interleukin-6.

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The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
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DNA methylation (DNAm) can predict inflammation levels, offering new insights into cognitive function. This DNAm proxy for interleukin-6 (IL-6) showed an association with cognitive decline, unlike measured IL-6.

Keywords:
Cognitive abilityDNA methylationEpigeneticsInflammationInterleukin-6

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Area of Science:

  • Epigenetics
  • Inflammation Biology
  • Cognitive Neuroscience

Background:

  • Heterogeneous results exist regarding chronic inflammation and cognitive function.
  • Variability in inflammatory mediators may cause misclassification of inflammation levels.
  • DNA methylation (DNAm) can index environmental exposures and serve as a proxy for inflammation.

Purpose of the Study:

  • To develop and validate a DNAm-based predictor for interleukin-6 (IL-6).
  • To investigate the association between this DNAm IL-6 proxy and cognitive functioning.
  • To explore the utility of DNAm in understanding inflammation's impact on health outcomes.

Main Methods:

  • Elastic net regression was used to develop a DNAm predictor for IL-6 in the Lothian Birth Cohort 1936 (N=875).
  • The predictor was validated in the independent Generation Scotland cohort (N=7028).
  • Associations with age and cognitive ability were assessed for both measured IL-6 and the DNAm proxy.

Main Results:

  • A 35 CpG site DNAm score accurately predicted IL-6 in the independent cohort (R2=4.4%).
  • Both measured IL-6 and the DNAm proxy increased with age.
  • Serum IL-6 did not correlate with cognitive ability, but the DNAm IL-6 score showed an inverse association with cognitive functioning (pFDR < 2 × 10-16).

Conclusions:

  • DNAm-based predictors can serve as effective proxies for inflammatory markers.
  • This approach may provide deeper insights into the relationship between inflammation and health.
  • The DNAm IL-6 score's association with cognitive function warrants further investigation.