Blood-based epigenome-wide analyses of cognitive abilities

Genome Biol. 2022 Jan 17;23(1):26. doi: 10.1186/s13059-021-02596-5.


Background: Blood-based markers of cognitive functioning might provide an accessible way to track neurodegeneration years prior to clinical manifestation of cognitive impairment and dementia.

Results: Using blood-based epigenome-wide analyses of general cognitive function, we show that individual differences in DNA methylation (DNAm) explain 35.0% of the variance in general cognitive function (g). A DNAm predictor explains ~4% of the variance, independently of a polygenic score, in two external cohorts. It also associates with circulating levels of neurology- and inflammation-related proteins, global brain imaging metrics, and regional cortical volumes.

Conclusions: As sample sizes increase, the ability to assess cognitive function from DNAm data may be informative in settings where cognitive testing is unreliable or unavailable.

Keywords: Cognitive ability; DNA methylation; EWAS; Epidemiology; Prediction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cognition
  • DNA Methylation
  • Epigenesis, Genetic*
  • Epigenome*
  • Genome-Wide Association Study / methods