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Genetic architecture of epigenetic and neuronal ageing rates in human brain regions
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Journal Article
Genetic architecture of epigenetic and neuronal ageing rates in human brain regions
2017
Overview
Identifying genes regulating the pace of epigenetic ageing represents a new frontier in genome-wide association studies (GWASs). Here using 1,796 brain samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based biomarkers of brain age: the epigenetic ageing rate and estimated proportion of neurons. Locus 17q11.2 is significantly associated (
P
=4.5 × 10
−9
) with the ageing rate across five brain regions and harbours a
cis
-expression quantitative trait locus for
EFCAB5
(
P
=3.4 × 10
−20
). Locus 1p36.12 is significantly associated (
P
=2.2 × 10
−8
) with epigenetic ageing of the prefrontal cortex, independent of the proportion of neurons. Our GWAS of the proportion of neurons identified two genome-wide significant loci (10q26 and 12p13.31) and resulted in a gene set that overlaps significantly with sets found by GWAS of age-related macular degeneration (
P
=1.4 × 10
−12
), ulcerative colitis (
P
<1.0 × 10
−20
), type 2 diabetes (
P
=2.8 × 10
−13
), hip/waist circumference in men (
P
=1.1 × 10
−9
), schizophrenia (
P
=1.6 × 10
−9
), cognitive decline (
P
=5.3 × 10
−4
) and Parkinson’s disease (
P
=8.6 × 10
−3
).
Studies on the ‘epigenetic clock’, a recently identified ageing biomarker, suggest that pathology might be linked to tissue-specific accelerated ageing. Here, the authors investigate ageing in the human brain and identify genetic loci associated with accelerated ageing in different brain regions.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/91
/ Adult
/ Age
/ Aged
/ Aging
/ Brain
/ Calcium-Binding Proteins - genetics
/ Calcium-Binding Proteins - metabolism
/ Child
/ Cognitive Dysfunction - genetics
/ Cognitive Dysfunction - metabolism
/ Cognitive Dysfunction - pathology
/ Female
/ Genome-Wide Association Study
/ Genomes
/ Humanities and Social Sciences
/ Humans
/ Infant
/ Male
/ Nerve Tissue Proteins - genetics
/ Nerve Tissue Proteins - metabolism
/ Neurodegenerative Diseases - genetics
/ Neurodegenerative Diseases - metabolism
/ Neurodegenerative Diseases - pathology
/ Science
