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Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)?three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Molecular Psychiatry, 2021, 26(8), 3884-3895

Editorial: Nature Publishing Group

 Año de publicación: 2021

Nº de páginas: 12

Tipo de publicación: Artículo de Revista

 DOI: 10.1038/s41380-019-0605-z

ISSN: 1359-4184,1476-5578

Url de la publicación: https://doi.org/10.1038/s41380-019-0605-z

Autoría

JIA, TIANYE

CHU, CONGYING

LIU, YUN

DONGEN, JENNY VAN

PAPASTERGIOS, EVANGELOS

ARMSTRONG, NICOLA J.

BASTIN, MARK E.

CARRILLO-ROA, TANIA

BRABER, ANOUK DEN

HARRIS, MATHEW

JANSEN, RICK

LIU, JINGYU

LUCIANO, MICHELLE

ORI, ANIL P. S.

ROBERTO ROIZ SANTIAÑEZ

RUGGERI, BARBARA

SARKISYAN, DANIIL

SHIN, JEAN

SUNGEUN, KIM

BENEDICTO CRESPO FACORRO