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Schlagwörter:
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Zusammenfassung:
Increasing age is tightly linked to decreased thickness of the human
neocortex. The biological mechanisms that mediate this effect are
hitherto unknown. The DNA methylome, as part of the epigenome,
contributes significantly to age-related phenotypic changes. Here, we
identify an epigenetic signature that is associated with cortical
thickness (P = 3.86 x 10(-8)) and memory performance in 533 healthy
young adults. The epigenetic effect on cortical thickness was replicated
in a sample comprising 596 participants with major depressive disorder
and healthy controls. The epigenetic signature mediates partially the
effect of age on cortical thickness (P < 0.001). A multilocus genetic
score reflecting genetic variability of this signature is associated
with memory performance (P = 0.0003) in 3,346 young and elderly healthy
adults. The genomic location of the contributing methylation sites
points to the involvement of specific immune system genes. The
decomposition of blood methylome-wide patterns bears considerable
potential for the study of brain-related traits.
