Blood-based epigenome-wide analyses of cognitive abilities

Abstract

We present a blood-based epigenome-wide association study and variance-components analysis of cognitive functions (n=9,162). Individual differences in DNA methylation (DNAm) accounted for up to 41.5% of the variance in cognitive functions; together, genetic and epigenetic markers accounted for up to 70.4% of the variance. A DNAm predictor accounted for 3.4% and 4.5% (P≤9.9x10-6) of the variance in general cognitive ability, independently of a polygenic score, in two external cohorts.

A comparison of blood and brain‐derived ageing and inflammation‐related DNA methylation signatures and their association with microglial burdens

“…It has been implicated in the regulation of gene expression and can itself be influenced by both genetic and environmental factors (Beck & Rakyan, 2008; Jaenisch & Bird, 2003). Genome‐wide DNAm patterns in the blood have been leveraged to index lifestyle traits, such as smoking (Liu et al, 2018; McCartney et al, 2018), and have been used to investigate diverse physical and mental health‐related phenotypes, including cognitive functioning (McCartney et al, 2022). In addition to this, by exploiting the manifest alterations in DNAm patterns with ageing, several DNAm‐based markers of age have been developed, which attempt to provide surrogate measures of biological ageing (Hannum et al, 2013; Horvath, 2013; Levine et al, 2018; Lu et al, 2019).…”

Associations of Socioeconomic Disparities With Buccal DNA-Methylation Measures Of Biological Aging

“…DNAm measures of biological aging that are most strongly predictive of disease, disability, and mortality are also consistently associated with social determinants of health (Oblak et al, 2021; Raffington & Belsky, 2022). In addition, there is evidence for social patterning of a DNAm measurement quantifying cognitive performance (McCartney et al, 2022), which parallels well-documented socioeconomic disparities in cognitive function across the life course (Lövdén et al, 2020). These DNAm measures open opportunities to study mechanisms of social disparities in physical and cognitive health and to guide the development and evaluation of interventions to address them.…”

A correlation map of genome-wide DNA methylation patterns between paired human brain and buccal samples

“…Accordingly, study designs exploiting DNAm profiles on a genome-wide scale—often referred to as epigenome-wide association studies (EWAS)—are becoming increasingly popular. Many EWAS aim to assess the relationship between DNAm patterns and certain brain-related phenotypes [ 2 , 3 ], such as neuropsychiatric traits [ 4 , 5 ], cognitive functions [ 6 , 7 ], and risk for neurodegenerative diseases [ 8 – 10 ], with the goal to better understand the biology and pathophysiology of the traits of interest. However, given that the primary organ of interest, the brain, is typically inaccessible in living individuals, many studies use tissues that are more readily available.…”

“…However, given that the primary organ of interest, the brain, is typically inaccessible in living individuals, many studies use tissues that are more readily available. While most DNAm studies use blood samples [ 3 , 6 , 7 , 10 ], it has been hypothesized that buccal [ 11 ] or saliva [ 12 ] samples may be more informative for EWAS of psychiatric phenotypes. One key advantage of using peripheral tissues as surrogates is that samples can be obtained from living individuals and do not require post-mortem sampling.…”