Blood-based epigenome-wide analyses of cognitive abilities

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 similar to 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.

Automated summary

By analyzing blood-based DNA methylation, individual differences in general cognitive function can be explained, which is important for tracking the development of neurodegenerative diseases. Assessing cognitive function using DNAm data may be valuable in environments where reliable or accessible cognitive testing is lacking.