Imprinting methylation predicts hippocampal volumes and hyperintensities and the change with age in later life

Abstract

Epigenetic imprinting is important for neurogenesis and brain function. Hippocampal volumes and brain hyperintensities in late life have been associated with early life circumstances. Epigenetic imprinting may underpin these associations. Methylation was measured at 982 sites in 13 imprinted locations in blood samples from a longitudinal cohort by bisulphite amplicon sequencing. Hippocampal volumes and hyperintensities were determined at age 64y and 72y using MRI. Hyperintensities were determined in white matter, grey matter and infratentorial regions. Permutation methods were used to adjust for multiple testing. At 64y, H19/IGF2 and NESPAS methylation predicted hippocampal volumes. PEG3 predicted hyperintensities in hippocampal grey matter, and white matter. GNASXL predicted grey matter hyperintensities. Changes with age were predicted for hippocampal volume (MEST1, KvDMR, L3MBTL, GNASXL), white matter (MEST1, PEG3) and hippocampal grey matter hyperintensities (MCTS2, GNASXL, NESPAS, L3MBTL, MCTS2, SNRPN, MEST1). Including childhood cognitive ability, years in education, or socioeconomic status as additional explanatory variables in regression analyses did not change the overall findings. Imprinting methylation in multiple genes predicts brain structures, and their change over time. These findings are potentially relevant to the development of novel tests of brain structure and function across the life-course, strategies to improve cognitive outcomes, and our understanding of early influences on brain development and function.

ADHD‐associated PARK2 copy number variants: A pilot study on gene expression and effects of supplementary deprivation in patient‐derived cell lines

“…Loss of function of peg3 in mouse placenta leads to low birth weight in pups (Creeth & John, 2020). In the ABC1936 cohort, it could be shown that PEG3 methylation predicted hyperintensities in hippocampal gray and white matter in the participants at age 64 and 72 (Lorgen‐Ritchie et al, 2021). As low birth weight is one of the best validated developmental risk factor for ADHD, in future studies, the birth history will be reported and it might be of interest to investigate the PEG3 methylation level as well.…”

Role of primary aging hallmarks in Alzheimer´s disease

“…However, oxo8dG and 5hmC in CGIs can induce DNA hypomethylation by inhibiting DNA methylation or activating the DNA demethylation processes 193 . Additionally, there is evidence showing that H19/IGF2 methylation states are potentially relevant to hippocampal structure and function across the life course 595 , 596 . Taken together, the decline in CTCF may cooperate with the gained methylation on ICR at the initial stage of AD to induce LOI of IGF2, which then may cause cascade events resulting in LOI of H19.…”

Identification of a Methylation Pattern in the SNRPN Gene Promoter and its Association with Semen Abnormality Among Iraqi Males

“…Genetics and environment can both have an impact on imprints. Variation in the sequence underlying the assessed epigenetic regions may have an impact on epigenetic states for genetic effects [17]. Imprinted genes have an unusual function in germ cells, in reprogramming events.…”