How epigenetics impacts stroke risk and outcomes through DNA methylation: A systematic review
Journal of Cerebral Blood Flow & Metabolism,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 27, 2025
The
impact
of
DNA
methylation
(DNAm)
on
epigenetics
has
gained
prominence
in
recent
years
due
to
its
potential
influence
ischemic
stroke
(IS)
and
treatment
outcomes.
DNAm
is
reversible
a
better
understanding
role
IS
could
help
identify
novel
therapeutic
targets.
aim
this
systematic
review
was
compile
the
available
data
risk
prognosis
explore
potential.
process
followed
PRISMA
criteria.
We
searched
Pubmed
Cochrane
databases
studies
that
used
hypothesis
free
methodological
approaches.
Of
459
identified,
34
met
inclusion
were
categorized
as
follows:
IS;
outcomes;
age.
Most
genotyping
array
technology
rather
than
whole-genome
sequencing.
testing
mainly
based
blood
samples.
involved
European
cohorts.
performed
at
single-center
with
recruitment
time
stroke.
In
few
studies,
health
status
determined
longitudinally.
This
shows
patients
are
biologically
older
expected
present
characteristic
patterns
related
These
be
develop
new
treatments
epidrugs.
Язык: Английский
Towards equitable brain genomics research, for us by us
Nature Neuroscience,
Год журнала:
2024,
Номер
27(6), С. 1021 - 1023
Опубликована: Май 20, 2024
Язык: Английский
RFMix-reader: Accelerated reading and processing for local ancestry studies
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 17, 2024
Local
ancestry
inference
is
a
powerful
technique
in
genetics,
revealing
population
history
and
the
genetic
basis
of
diseases.
It
particularly
valuable
for
improving
eQTL
discovery
fine-mapping
admixed
populations.
Despite
widespread
use
RFMix
software
local
inference,
large-scale
genomic
studies
face
challenges
high
memory
consumption
processing
times
when
handling
output
files.
Язык: Английский
Integrated Single-Cell Multiomic Profiling of Caudate Nucleus Suggests Key Mechanisms in Alcohol Use Disorder
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 6, 2024
Abstract
Alcohol
use
disorder
(AUD)
induces
complex
transcriptional
and
regulatory
changes
across
multiple
brain
regions
including
the
caudate
nucleus,
which
remains
understudied.
Using
paired
single-nucleus
RNA-seq
ATAC-seq
on
samples
from
143
human
postmortem
brains,
74
with
AUD,
we
identified
17
distinct
cell
types.
We
found
that
a
significant
portion
of
alcohol-induced
in
gene
expression
occurred
through
altered
chromatin
accessibility.
Notably,
novel
accessibility
differences
medium
spiny
neurons,
impacting
pathways
such
as
RNA
metabolism
immune
response.
A
small
cluster
D1/D2
hybrid
neurons
showed
differences,
suggesting
unique
role
AUD.
Microglia
exhibited
activation
states
deviating
classical
M1/M2
designations,
astrocytes
entered
reactive
state
partially
regulated
by
JUND
,
affecting
glutamatergic
synapse
pathways.
Oligodendrocyte
dysregulation,
driven
part
OLIG2
was
linked
to
demyelination
increased
TGF-β1
signaling
microglia
astrocytes.
also
observed
microglia-astrocyte
communication
via
IL-1β
pathway.
Leveraging
our
multiomic
data,
performed
type-specific
quantitative
trait
loci
analysis,
integrating
public
genome-wide
association
studies
identify
AUD
risk
genes
ADAL
PPP2R3C
providing
direct
link
between
genetic
variants,
accessibility,
These
findings
not
only
provide
new
insights
into
cellular
mechanisms
related
but
demonstrate
broader
utility
large-scale
uncovering
regulation
diverse
types,
has
implications
beyond
substance
field.
Язык: Английский
The neuroscience of mental illness: Building toward the future
Cell,
Год журнала:
2024,
Номер
187(21), С. 5858 - 5870
Опубликована: Окт. 1, 2024
Язык: Английский
Integrated Transcriptome Analysis Reveals Novel Molecular Signatures for Schizophrenia Characterization
Advanced Science,
Год журнала:
2024,
Номер
12(2)
Опубликована: Ноя. 20, 2024
Abstract
Schizophrenia
(SCZ)
is
a
complex
psychiatric
disorder
presenting
challenges
for
characterization.
The
current
study
aimed
to
identify
and
evaluate
disease‐responsive
essential
genes
(DREGs)
enhance
the
molecular
characterization
of
SCZ.
RNA‐sequencing
data
from
PsychENCODE
(536
SCZ
patients,
832
controls)
peripheral
blood
transcriptome
144
recruited
subjects
(59
6
non‐SCZ
79
are
analyzed.
Shared
differential
expression
obtained
using
three
algorithms.
Support
vector
machine
(SVM)‐based
recursive
feature
elimination
employed
DREGs.
biological
relevance
these
DREGs
examined
through
protein–protein
interaction
network,
pathway
enrichment,
polygenic
scoring,
brain
tissue
expression.
Key
validated
in
animal
models.
A
DREGs‐based
machine‐learning
model
developed
its
performance
assessed
multiple
datasets.
analysis
identified
184
forming
an
interconnected
network
involved
synaptic
plasticity,
inflammation,
neuronal
development,
neurotransmission.
exhibited
distinct
SCZ‐related
regions
Their
genetic
contributions
comparable
genome‐wide
risk
scores.
DREG‐based
SVM
demonstrated
high
(AUC
85%
characterization,
79%
specificity).
These
findings
provide
new
insights
into
mechanisms
underlying
emphasize
potential
improving
Язык: Английский
Cell type-specific expression of angiotensin receptors in the human lung with implications for health, aging, and chronic disease
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 22, 2024
The
renin-angiotensin
system
is
a
highly
characterized
integrative
pathway
in
mammalian
homeostasis
whose
clinical
spectrum
has
been
expanded
to
lung
disorders
such
as
chronic
obstructive
pulmonary
disease
(COPD)-emphysema,
idiopathic
fibrosis
(IPF),
and
COVID
pathogenesis.
Despite
this
widespread
interest,
specific
localization
of
receptor
family
the
limited,
partially
due
imprecision
available
antibody
reagents.
In
study,
we
establish
expression
pattern
two
predominant
angiotensin
receptors
human
lung,
Язык: Английский
The role of interferon signaling in neurodegeneration and neuropsychiatric disorders
Frontiers in Psychiatry,
Год журнала:
2024,
Номер
15
Опубликована: Окт. 3, 2024
Recent
advances
in
transcriptomics
research
have
uncovered
heightened
interferon
(IFN)
responses
neurodegenerative
diseases
including
Alzheimer's
disease,
primary
tauopathy,
Parkinson's
TDP-43
proteinopathy,
and
related
mouse
models.
Augmented
IFN
signaling
is
now
relatively
well
established
for
microglia
these
contexts,
but
emerging
work
has
highlighted
a
novel
role
IFN-responsive
T
cells
the
brain
peripheral
blood
some
types
of
neurodegeneration.
These
findings
complement
body
literature
implicating
dysregulated
neuropsychiatric
disorders
major
depression
post-traumatic
stress
disorder.
In
this
review,
we
will
characterize
integrate
our
understanding
discuss
how
sex
ancestry
modulate
response,
examine
potential
mechanistic
explanations
upregulation
antiviral-like
pathways
seemingly
non-viral
neurological
psychiatric
disorders.
Язык: Английский
Reported race-associated differences in control and schizophrenia post-mortem brain transcriptomes implicate stress-related and neuroimmune pathways
Frontiers in Molecular Neuroscience,
Год журнала:
2024,
Номер
17
Опубликована: Ноя. 18, 2024
Background
The
molecular
mechanisms
underlying
racial
disparities
in
schizophrenia
(SCZ)
illness
courses
and
outcomes
are
poorly
understood.
While
these
differences
thought
to
arise
partly
through
stressful
social
gradients,
little
is
known
about
how
reflected
the
brain,
nor
they
might
underlie
disparate
psychiatric
outcomes.
Methods
To
better
understand
neuro-molecular
correlates
of
SCZ,
their
overlap,
we
analyzed
post-mortem
dorsolateral
prefrontal
cortex
(DLPFC)
RNAseq
data
from
two
racially
diverse
cohorts
CommonMind
Consortium
(235
reported
Black
546
White,
322
SCZ
cases
459
controls)
using
differential
expression
gene
set
variation
analyses.
Results
We
observed
brain
that
were
consistent
across
race.
A
combined
mega-analysis
identified
1,514
genes
with
(DE)
between
race
groups
after
accounting
for
diagnosis
other
covariates.
Functional
enrichment
analyses
upregulation
involved
stress
immune
response,
highlighting
potential
role
environmental
groups.
In
a
race-by-diagnosis
interaction
analysis,
no
individual
passed
statistical
significance.
However,
109
sets
showed
statistically
significant
differences,
implicating
metabolic
pathways.
Conclusion
Our
results
suggest
uniquely
perturbed
identify
several
candidate
pathways
associated
race-dependent
manner.
underscore
importance
cohort
ascertainment
capture
population-level
pathogenesis.
Язык: Английский
Ancestry-specific gene expression in peripheral monocytes mediates risk of neurodegenerative disease
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 22, 2024
Abstract
It
is
hypothesised
that
peripheral
immune
states
responding
to
regional
environmental
triggers
contribute
central
neurodegeneration.
Region-specific
genetic
selection
pressures
require
this
hypothesis
be
assessed
in
an
ancestry
specific
manner.
Here
we
utilise
genome-wide
association
studies
and
expression
quantitative
trait
loci
from
African,
East
Asian
European
ancestries
show
genes
causing
neurodegeneration
are
preferentially
expressed
innate
rather
than
adaptive
cells,
of
these
mediates
the
risk
neurodegenerative
disease
monocytes
ancestry-specific
Язык: Английский