Abstract
BackgroundEpigenetic mechanisms are important in aging and may be involved in late-life changes in cognitive abilities. We conducted an epigenome-wide association study of leukocyte DNA methylation in relation to level and change in cognitive abilities, from midlife through late life in 535 Swedish twins.ResultsMethylation levels were measured with the Infinium Human Methylation 450 K or Infinium MethylationEPIC array, and all sites passing quality control on both arrays were selected for analysis (n = 250,816). Empirical Bayes estimates of individual intercept (age 65), linear, and quadratic change were obtained from latent growth curve models of cognitive traits and used as outcomes in linear regression models. Significant sites (p < 2.4 × 10–7) were followed up in between-within twin pair models adjusting for familial confounding and full-growth modeling. We identified six significant associations between DNA methylation and level of cognitive abilities at age 65: cg18064256 (PPP1R13L) with processing speed and spatial ability; cg04549090 (NRXN3) with spatial ability; cg09988380 (POGZ), cg25651129 (-), and cg08011941 (ENTPD8) with working memory. The genes are involved in neuroinflammation, neuropsychiatric disorders, and ATP metabolism. Within-pair associations were approximately half that of between-pair associations across all sites. In full-growth curve models, associations between DNA methylation and cognitive level at age 65 were of small effect sizes, and associations between DNA methylation and longitudinal change in cognitive abilities of very small effect sizes.ConclusionsLeukocyte DNA methylation was associated with level, but not change in cognitive abilities. The associations were substantially attenuated in within-pair analyses, indicating they are influenced in part by genetic factors.
Highlights
Epigenetic mechanisms are important in aging and may be involved in late-life changes in cognitive abilities
Study population The study was based on 535 individuals from the Swedish Adoption/Twin Study of Aging (SATSA) [11], a substudy of the population-based Swedish Twin Registry (STR) [12]
This may indicate that the findings represent systemic effects, either with long-term effects on cognitive level, or themselves affected by factors related to cognitive abilities
Summary
Epigenetic mechanisms are important in aging and may be involved in late-life changes in cognitive abilities. We conducted an epigenome-wide association study of leukocyte DNA methylation in relation to level and change in cognitive abilities, from midlife through late life in 535 Swedish twins. Starnawska et al [9] studied blood DNA methylation in relation to level and 10-year linear change in general cognitive ability in 243 monozygotic twin pairs with a mean age of 70 at last measurement. The first EWAS of cognition in a Chinese sample was conducted by Wang et al, who studied blood DNA methylation and cognitive function in 30 monozygotic twin pairs with a median age of 52 years [10]
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