Pleiotropic Effects of Grm7/GRM7 in Shaping Neurodevelopmental Pathways and the Neural Substrate of Complex Behaviors and Disorders
Beatrix Gyetvai,
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Csaba Vadász
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Biomolecules,
Journal Year:
2025,
Volume and Issue:
15(3), P. 392 - 392
Published: March 8, 2025
Natural
gene
variants
of
metabotropic
glutamate
receptor
subtype
7
(Grm7),
coding
for
mGluR7,
affect
individuals’
alcohol-drinking
preference.
Psychopharmacological
investigations
have
suggested
that
mGluR7
is
also
involved
in
responses
to
cocaine,
morphine,
and
nicotine
exposures.
We
review
the
pleiotropic
effects
Grm7
principle
recombinant
quantitative
trait
locus
introgression
(RQI),
which
led
discovery
first
mammalian
accounting
Grm7/GRM7
can
play
important
roles
ontogenesis,
brain
development,
predisposition
addiction.
It
other
behavioral
phenotypes,
including
emotion,
stress,
motivated
cognition,
defensive
behavior,
pain-related
symptoms.
This
identified
pleiotropy
modulation
neurobehavioral
processes
by
variations
Grm7/GRM7.
Patterns
genes
form
oligogenic
architectures
whosecombined
additive
interaction
significantly
predispose
individuals
expressions
disorders.
Identifying
characterizing
are
necessary
understanding
complex
traits.
requires
tasks,
such
as
discovering
identifying
novel
genetic
elements
architecture,
unsuitable
AI
but
require
classical
experimental
genetics.
Language: Английский
5. Collaborative Study on the Genetics of Alcoholism: Functional genomics
Genes Brain & Behavior,
Journal Year:
2023,
Volume and Issue:
22(5)
Published: Aug. 2, 2023
Abstract
Alcohol
Use
Disorder
is
a
complex
genetic
disorder,
involving
genetic,
neural,
and
environmental
factors,
their
interactions.
The
Collaborative
Study
on
the
Genetics
of
Alcoholism
(COGA)
has
been
investigating
these
factors
identified
putative
alcohol
use
disorder
risk
genes
through
genome‐wide
association
studies.
In
this
review,
we
describe
advances
made
by
COGA
in
elucidating
functional
changes
induced
using
multimodal
approaches
with
human
cell
lines
brain
tissue.
These
studies
involve
gene
regulation
lymphoblastoid
cells
from
participants
post‐mortem
tissues.
High
throughput
reporter
assays
are
being
used
to
identify
single
nucleotide
polymorphisms
which
alternate
alleles
differ
driving
expression.
Specific
(both
coding
or
noncoding)
have
modeled
pluripotent
stem
derived
evaluate
effects
variants
transcriptomics,
neuronal
excitability,
synaptic
physiology,
response
ethanol
neurons
individuals
without
disorder.
We
provide
perspective
future
studies,
such
as
polygenic
scores
populations
cell‐derived
signaling
pathways
related
responses
alcohol.
Starting
loci
associated
demonstrated
that
integration
data
within
can
reveal
mechanisms
linking
genomic
potential
targets
for
treatments.
Language: Английский
Polygenic Risk for Alcohol Use Disorder Affects Cellular Responses to Ethanol Exposure in a Human Microglial Cell Model
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Feb. 21, 2024
Abstract
Polygenic
risk
scores
(PRS)
assess
genetic
susceptibility
to
Alcohol
Use
Disorder
(AUD),
yet
their
molecular
implications
remain
underexplored.
Neuroimmune
interactions,
particularly
in
microglia,
are
recognized
as
significant
contributors
AUD
pathophysiology.
We
investigated
the
interplay
between
PRS
and
ethanol
human
microglia
derived
from
iPSCs
individuals
with
high-
or
low-PRS
(HPRS
LPRS)
of
AUD.
Ethanol
exposure
induced
elevated
CD68
expression
morphological
changes
differential
responses
HPRS
LPRS
microglial
cells.
Transcriptomic
analysis
revealed
differences
MHCII
complex
phagocytosis-related
genes
following
exposure;
cells
displayed
enhanced
phagocytosis
increased
CLEC7A
expression,
unlike
Synapse
numbers
co-cultures
neurons
after
alcohol
were
lower
HRPS
co-cultures,
suggesting
possible
excess
synapse
pruning.
This
study
provides
insights
into
intricate
relationship
PRS,
ethanol,
function,
potentially
influencing
neuronal
functions
developing
Language: Английский
Polygenic risk for alcohol use disorder affects cellular responses to ethanol exposure in a human microglial cell model
Science Advances,
Journal Year:
2024,
Volume and Issue:
10(45)
Published: Nov. 8, 2024
Polygenic
risk
scores
(PRSs)
assess
genetic
susceptibility
to
alcohol
use
disorder
(AUD),
yet
their
molecular
implications
remain
underexplored.
Neuroimmune
interactions,
particularly
in
microglia,
are
recognized
as
notable
contributors
AUD
pathophysiology.
We
investigated
the
interplay
between
PRS
and
ethanol
human
microglia
derived
from
iPSCs
individuals
with
high-PRS
(diagnosed
AUD)
or
low-PRS
(unaffected).
Ethanol
exposure
induced
elevated
CD68
expression
morphological
changes
differential
responses
microglial
cells.
Transcriptomic
analysis
revealed
differences
MHCII
complex
phagocytosis-related
genes
following
exposure;
cells
displayed
enhanced
phagocytosis
increased
Language: Английский
Collaborative study on the genetics of alcoholism: The strength of collaboration, team science, and longitudinal data
Genes Brain & Behavior,
Journal Year:
2023,
Volume and Issue:
22(5)
Published: Sept. 19, 2023
Abstract
This
issue
contains
a
series
of
articles
describing
the
various
resources,
studies,
results,
and
future
directions
for
collaborative
study
on
genetics
alcoholism
(COGA).
The
integrative
approach
initiated
by
this
group
~30
years
ago
serves
as
an
excellent
example
strength
team
science.
Individually,
aspects
COGA
would
be
limited
in
their
impact
toward
improved
understanding
alcohol
use
disorder.
Collectively,
wholistic
which
spans
deep
longitudinal
phenotypic
assessments
families
to
include
application
large‐scale
omics
technologies
cell‐culture
based
molecular
studies
has
demonstrated
power
working
together.
Language: Английский