Human Molecular Genetics,
Journal Year:
2019,
Volume and Issue:
29(1), P. 159 - 167
Published: Oct. 23, 2019
Schizophrenia
is
a
complex
highly
heritable
disorder.
Genome-wide
association
studies
(GWAS)
have
identified
multiple
loci
that
influence
the
risk
of
developing
schizophrenia,
although
causal
variants
driving
these
associations
and
their
impacts
on
specific
genes
are
largely
unknown.
We
identify
significant
correlation
between
schizophrenia
expression
at
89
in
dorsolateral
prefrontal
cortex
(P
≤
9.43
×
10-6),
including
20
novel
genes.
Genes
whose
correlate
with
were
enriched
for
those
involved
abnormal
CNS
synaptic
transmission
(PFDR
=
0.02)
antigen
processing
presentation
peptide
via
MHC
class
I
0.02).
Within
set,
we
individual
candidate
to
which
assign
direction
changes
schizophrenia.
The
findings
provide
strong
candidates
experimentally
probing
molecular
basis
pathology
Science,
Journal Year:
2024,
Volume and Issue:
384(6698)
Published: May 23, 2024
The
molecular
organization
of
the
human
neocortex
historically
has
been
studied
in
context
its
histological
layers.
However,
emerging
spatial
transcriptomic
technologies
have
enabled
unbiased
identification
transcriptionally
defined
domains
that
move
beyond
classic
cytoarchitecture.
We
used
Visium
gene
expression
platform
to
generate
a
data-driven
neuroanatomical
atlas
across
anterior-posterior
axis
dorsolateral
prefrontal
cortex.
Integration
with
paired
single-nucleus
RNA-sequencing
data
revealed
distinct
cell
type
compositions
and
cell-cell
interactions
domains.
Using
PsychENCODE
publicly
available
data,
we
mapped
enrichment
types
genes
associated
neuropsychiatric
disorders
discrete
Nature Neuroscience,
Journal Year:
2024,
Volume and Issue:
27(6), P. 1075 - 1086
Published: April 22, 2024
Abstract
Human
brain
organization
involves
the
coordinated
expression
of
thousands
genes.
For
example,
first
principal
component
(C1)
cortical
transcription
identifies
a
hierarchy
from
sensorimotor
to
association
regions.
In
this
study,
optimized
processing
Allen
Brain
Atlas
revealed
two
new
components
gene
architecture,
C2
and
C3,
which
are
distinctively
enriched
for
neuronal,
metabolic
immune
processes,
specific
cell
types
cytoarchitectonics,
genetic
variants
associated
with
intelligence.
Using
additional
datasets
(PsychENCODE,
Cell
BrainSpan),
we
found
that
C1–C3
represent
generalizable
transcriptional
programs
within
cells
differentially
phased
during
fetal
postnatal
development.
Autism
spectrum
disorder
schizophrenia
were
specifically
C1/C2
respectively,
across
neuroimaging,
differential
genome-wide
studies.
Evidence
converged
especially
in
support
C3
as
normative
program
adolescent
development,
can
lead
atypical
supragranular
connectivity
people
at
high
risk
schizophrenia.
Cell Reports,
Journal Year:
2025,
Volume and Issue:
44(2), P. 115300 - 115300
Published: Feb. 1, 2025
The
dentate
gyrus
of
the
hippocampus
is
important
for
many
cognitive
functions,
including
learning,
memory,
and
mood.
Here,
we
present
transcriptome-wide
spatial
gene
expression
maps
human
investigate
age-associated
changes
across
lifespan.
Genes
associated
with
neurogenesis
extracellular
matrix
are
enriched
in
infants
decline
throughout
development
maturation.
Following
infancy,
inhibitory
neuron
markers
increase,
cellular
proliferation
decrease.
We
also
identify
spatio-molecular
signatures
that
support
existing
evidence
protracted
maturation
granule
cells
during
adulthood
increases
neuroinflammation-related
expression.
Our
findings
notion
hippocampal
neurogenic
niche
undergoes
major
following
infancy
molecular
regulators
brain
aging
glial-
neuropil-enriched
tissue.
Nature Communications,
Journal Year:
2020,
Volume and Issue:
11(1)
Published: Nov. 3, 2020
Abstract
Cigarette
smoking
is
the
leading
cause
of
preventable
morbidity
and
mortality.
Genetic
variation
contributes
to
initiation,
regular
smoking,
nicotine
dependence,
cessation.
We
present
a
Fagerström
Test
for
Nicotine
Dependence
(FTND)-based
genome-wide
association
study
in
58,000
European
or
African
ancestry
smokers.
observe
five
significant
loci,
including
previously
unreported
loci
MAGI2/GNAI1
(rs2714700)
TENM2
(rs1862416),
extend
reported
other
traits
dependence.
Using
heaviness
index
from
UK
Biobank
(
N
=
33,791),
rs2714700
consistently
associated;
rs1862416
not
associated,
likely
reflecting
dependence
features
captured
by
index.
Both
variants
influence
nearby
gene
expression
(rs2714700/
MAGI2-AS3
hippocampus;
rs1862416/
lung),
genes
spanning
dependence-associated
enriched
cerebellum.
(SNP-based
heritability
8.6%)
genetically
correlated
with
18
r
g
0.40–1.09)
co-morbidities.
Our
results
highlight
dependence-specific
emphasizing
FTND
as
composite
phenotype
that
expands
genetic
knowledge
smoking.
Molecular Psychiatry,
Journal Year:
2020,
Volume and Issue:
25(11), P. 2695 - 2711
Published: Aug. 7, 2020
Abstract
Despite
extensive
genetic
and
neuroimaging
studies,
detailed
cellular
mechanisms
underlying
schizophrenia
bipolar
disorder
remain
poorly
understood.
Recent
progress
in
single-cell
RNA
sequencing
(scRNA-seq)
technologies
enables
identification
of
cell-type-specific
pathophysiology.
However,
its
application
to
psychiatric
disorders
is
challenging
because
methodological
difficulties
analyzing
human
brains
the
confounds
due
a
lifetime
illness.
Brain
organoids
derived
from
induced
pluripotent
stem
cells
(iPSCs)
patients
are
powerful
avenue
investigate
pathophysiological
processes.
Here,
we
generated
iPSC-derived
cerebral
monozygotic
twins
discordant
for
psychosis.
scRNA-seq
analysis
revealed
enhanced
GABAergic
specification
reduced
cell
proliferation
following
diminished
Wnt
signaling
patient,
which
was
confirmed
forebrain
neuronal
cells.
Two
additional
twin
pairs
also
excess
patients’
neural
progenitor
With
well-controlled
background,
our
data
suggest
that
unbalanced
excitatory
inhibitory
neurons
during
cortical
development
underlies
psychoses.
