The
radial
unit
hypothesis
describes
how
glia
in
fetal
development
influence
cortical
size
and
structure
adulthood.
This
serves
as
a
framework
to
interpret
the
molecular
cellular
mechanisms
of
human
genetic
variation
associated
with
well
fixed
differences
between
modern
humans
archaic
or
related
species
contributing
brain
structure.
Cortical-structure
rare
variants
have
been
shown
change
composition
by
altering
glial
fate
decisions
disrupt
architecture
through
aberrant
scaffolds,
measured
mice
pluripotent
stem
cell
systems.
common
recently
identified
genome-wide
association
studies
are
enriched
regulatory
elements
cells.
Some
loci
surface
area
linked
genes
regulating
cycle
control
via
quantitative
trait
loci.
Though
study
involved
evolution
is
still
at
early
stages,
several
examples
whereby
these
alter
function
presumably
increase
size.
Future
research
gene
regulation
will
accelerate
understanding
variants.
Brain,
Год журнала:
2021,
Номер
145(1), С. 378 - 387
Опубликована: Май 28, 2021
Abstract
The
biological
mechanisms
underlying
the
greater
prevalence
of
autism
spectrum
disorder
in
males
than
females
remain
poorly
understood.
One
hypothesis
posits
that
this
female
protective
effect
arises
from
genetic
load
for
differentially
impacting
male
and
brains.
To
test
hypothesis,
we
investigated
impact
cumulative
risk
on
functional
brain
connectivity
a
balanced
sample
boys
girls
with
typically
developing
(127
youth,
ages
8–17).
Brain
analyses
focused
salience
network,
core
intrinsic
network
which
has
previously
been
implicated
disorder.
effects
polygenic
were
significantly
modulated
by
participant
sex,
influencing
without
but
not
girls.
These
findings
support
genes
interact
sex
differential
processes,
thereby
contributing
to
bias
proposing
an
neurobiological
mechanism
effect.
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Март 17, 2023
ABSTRACT
Recent
studies
suggest
shared
genetic
effects
on
both
schizophrenia
and
brain
structure,
but
it
has
been
challenging
to
specify
which
genes
mediate
this
pleiotropic
association.
We
accessed
genome-wide
association
data
(N=69,369
cases;
236,642
controls),
three
magnetic
resonance
imaging
(MRI)
metrics
(surface
area,
cortical
thickness,
neurite
density
index)
measured
at
180
areas
(N=36,843).
Using
Hi-C-coupled
MAGMA,
we
identified
61
that
were
significantly
associated
with
one
or
more
MRI
metrics.
Whole
genome
analysis
demonstrated
significant
covariation
between
area
thickness
of
most
regions.
Genetic
similarity
was
strongly
coupled
covariance
their
metrics,
regional
phenotypes
greatest
in
the
hubs
corresponding
structural
network.
Three
genomic
regions,
chromosomes
3p21,
17q21
11p11,
enriched
for
neurodevelopmental
processes
consistently
implicated
these
associations
network
organization.
Journal of Personalized Medicine,
Год журнала:
2021,
Номер
11(2), С. 121 - 121
Опубликована: Фев. 13, 2021
Since
patients
with
schizophrenia
(SZ)
and
bipolar
disorder
(BD)
share
many
biological
features,
detecting
biomarkers
that
differentiate
SZ
BD
is
crucial
for
optimized
treatments.
High-resolution
magnetic
resonance
imaging
(MRI)
suitable
subtle
brain
structural
differences
in
psychiatric
disorders.
In
the
present
study,
we
adopted
a
neuroanatomically
defined
manually
delineated
region
of
interest
(ROI)
method
to
evaluate
amygdalae,
hippocampi,
Heschl’s
gyrus
(HG),
planum
temporale
(PT),
because
these
regions
are
development
BD.
ROI
volumes
were
measured
using
high
resolution
MRI
31
healthy
subjects
(HS),
23
patients,
21
patients.
Right
hippocampal
differed
significantly
among
groups
(HS
>
SZ),
whereas
left
lower
than
HS
=
SZ).
Volumes
HG,
PT
did
not
differ
three
groups.
For
clinical
correlations,
there
no
significant
associations
between
demographics/clinical
symptoms.
Our
study
revealed
volume
BD,
suggest
right
potential
biomarker
differentiation
Magnetic Resonance in Medical Sciences,
Год журнала:
2021,
Номер
21(4), С. 539 - 552
Опубликована: Авг. 18, 2021
Schizophrenia
is
a
common
severe
psychiatric
disorder
that
affects
approximately
1%
of
general
population
through
the
life
course.
Historically,
in
Kraepelin's
time,
schizophrenia
was
disease
unit
conceptualized
as
dementia
praecox;
however,
since
then,
concept
has
changed.
Recent
MRI
studies
had
shown
neuropathology
brain
this
characterized
by
mild
progression
before
and
after
onset
disease,
alterations
were
relatively
smaller
than
assumed.
Although
genetic
factors
contribute
to
schizophrenia,
which
are
thought
be
trait
differences,
other
changes
include
diseases.
Furthermore,
it
been
differences
specific
small
compared
changes,
such
those
caused
development,
aging,
gender.
In
addition,
participant
factors,
machine
imaging
protocol
could
affect
signals,
should
addressed
multi-site
studies.
advances
modalities,
multi-shell
diffusion-weighted
imaging,
magnetic
resonance
spectroscopy,
multimodal
analysis,
may
candidates
sharpen
characterization
schizophrenia-specific
provide
new
insights.
The
Brain/MINDS
Beyond
Human
Brain
(BMB-HBM)
project
launched
considering
noises
irrespective
pathologies
includes
future
perspectives
for
various
neurological
disorders.
sites
use
restricted
machines
harmonized
multi-modal
protocols,
standardized
image
preprocessing,
traveling
subject
harmonization.
Data
sharing
public
will
planned
FY
2024.
future,
we
believe
combining
high-quality
human
dataset
with
data,
randomized
controlled
trials,
non-human
primates
animal
models
enable
us
understand
elucidate
its
neural
bases
therapeutic
targets,
tools
clinical
application
at
bedside.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Апрель 25, 2022
Abstract
Background
Genetic
variation
influences
both
chromatin
accessibility,
assessed
in
accessibility
quantitative
trait
loci
(caQTL)
studies,
and
gene
expression,
expression
QTL
(eQTL)
studies.
variants
can
impact
either
nearby
genes
(local
eQTLs)
or
distal
(trans
eQTLs).
Colocalization
between
caQTL
eQTL,
local-
distant-eQTLs
suggests
that
they
share
causal
variants.
However,
pairwise
colocalization
these
molecular
QTLs
does
not
guarantee
a
relationship.
Mediation
analysis
be
applied
to
assess
the
evidence
supporting
causality
versus
independence
QTLs.
Given
function
of
cell-type-specific,
we
performed
mediation
analyses
find
epigenetic
regulatory
pathways
for
within
two
major
cell
types
developing
human
cortex,
progenitors
neurons.
Results
We
found
168
38
were
mediated
by
neurons,
respectively.
also
781
200
downstream
upstream
Moreover,
discovered
genetic
locus
associated
with
inter-individual
differences
brain
structure
showed
SLC26A7
through
identifying
mechanisms
common
variant
association
trait.
Conclusions
In
this
study,
identified
cell-type-specific
networks
whereby
impacts
on
expression.
Identification
paths
will
enable
prioritizing
actionable
targets
perturbing
key
processes
during
neurodevelopment.
Abstract
Motivation
Imaging
genetics
integrates
imaging
and
genetic
techniques
to
examine
how
variations
influence
the
function
structure
of
organs
like
brain
or
heart,
providing
insights
into
their
impact
on
behavior
disease
phenotypes.
The
use
organ-wide
endophenotypes
has
increasingly
been
used
identify
potential
genes
associated
with
complex
disorders.
However,
analyzing
data
alongside
presents
two
significant
challenges:
high
dimensionality
relationships.
To
address
these
challenges,
we
propose
a
novel,
nonlinear
inference
framework
designed
partially
mitigate
issues.
Results
We
functional
partial
least
squares
through
distance
covariance
(FPLS-DC)
for
efficient
genome
wide
analyses
It
consists
components.
first
component
utilizes
FPLS-derived
base
functions
reduce
image
while
screening
markers.
second
maximizes
correlation
between
markers
projected
data,
which
is
linear
combination
FPLS-basis
functions,
using
simulated
annealing
algorithm.
In
addition,
proposed
an
iterative
FPLS-DC
method
based
framework,
effectively
overcomes
inter-gene
analysis.
efficiently
approximate
null
distribution
test
statistics
gamma
approximation.
Compared
existing
methods,
offers
computational
statistical
efficiency
handling
large-scale
genetics.
real-world
applications,
our
successfully
detected
variants
hippocampus,
demonstrating
its
value
as
toolbox
studies.
Availability
implementation
opens
up
new
research
avenues
valuable
high-dimensional
data.
it
serves
useful
tool
scientific
analysis
in
practical
applications
within
field
research.
R
package
available
Github:
https://github.com/BIG-S2/FPLSDC.
