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Using blood-based epigenome-wide analyses of general cognitive function (g; n=9,162) we show that individual differences in DNA methylation (DNAm) explain 35.0% of the variance in g. A DNAm predictor explains ~4% of the variance in g, 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. As sample sizes increase, our ability to assess cognitive function from DNAm data may be informative in settings where cognitive testing is unreliable or unavailable.

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