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Updated: Oct 6, 2025
Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain
Published on: July 12, 2012
Blood-based epigenome-wide analyses of cognitive abilities
Daniel L McCartney1, Robert F Hillary2, Eleanor L S Conole3,4
1Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK. daniel.mccartney@ed.ac.uk.
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.
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