bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 21, 2024
Abstract
The
genetic
architecture
of
human
brain
networks
is
central
to
understanding
the
organization
and
evolution
cortex,
causal
relationships
between
structure
function,
pathogenesis
heritable
neuropsychiatric
disorders.
However,
current
genetics
remains
fragmented.
Here,
we
investigated
common
effects
on
Morphometric
INverse
Divergence
(MIND),
a
biologically-validated,
heritable,
multimodal
MRI
metric
inter-areal
similarity
connectivity.
Using
discovery
dataset
(N
>
30,000
adults),
estimated
subject-specific
MIND
from
multivariate
distributions
four
features
at
each
23
cortical
areas
performed
genome-wide
association
studies
(GWAS)
276
edges.
These
edge-level
were
highly
replicated
by
parallel
GWAS
an
independent
validation
18,000
adults).
We
found
that
strong
correlations
multiple
edges
largely
reducible
two
gradients
genetically-determined
similarity,
which
was
aligned
with
geodesic
distance
one
phylogenetically
primitive
(paleocortex
archicortex)
predicted
dual
origin
theory
evolution.
Genetic
more
than
comparable
derived
functional
connectivity
networks;
paleocortical
trend
genetically
correlated
with,
causally
predictive
of,
Finally,
identified
global
local
both
nine
clinical
diagnoses
or
biomedical
traits,
indicating
normative
pleiotropically
associated
inherited
risk
disorders
systemic
metabolic
immune
traits.
results
provide
fresh
insight
into
origins
cortex
their
implications
for
function
health.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Ноя. 13, 2024
Abstract
Several
cardiovascular
traits
and
diseases
co-occur
with
Alzheimer’s
disease.
We
mapped
their
shared
genetic
architecture
using
multi-trait
genome-wide
association
studies.
Subsequent
fine-mapping
colocalisation
highlighted
16
loci
associated
both
diseases.
prioritised
rs11786896,
which
colocalised
disease,
atrial
fibrillation
expression
of
PLEC
in
the
heart
left
ventricle,
rs7529220,
C1Q
family
genes.
Single-cell
RNA-sequencing
data,
co-expression
network
protein-protein
interaction
analyses
provided
evidence
for
different
mechanisms
,
is
upregulated
ventricular
endothelium
cardiomyocytes
failure
brain
astrocytes
Similar
common
are
implicated
macrophages
microglia
These
findings
highlight
inflammatory
pleomorphic
risk
determinants
co-occurrence
suggest
PLEC,
interacting
proteins
as
potential
therapeutic
targets.
Neuroscience Letters,
Год журнала:
2024,
Номер
839, С. 137935 - 137935
Опубликована: Авг. 14, 2024
Bipolar
disorder
(BD)
is
a
debilitating
neuropsychiatric
disorder,
which
associated
with
genetic
variation
through
"vast
but
mixed"
Genome-Wide
Association
Studies
(GWAS).
Transcriptome-Wide
Study
(TWAS)
more
effective
in
explaining
factors
that
influence
complex
diseases
and
can
help
identifying
risk
genes
reliably.
So,
this
study
aims
to
identify
potential
BD
pedigrees
TWAS.
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 31, 2024
Abstract
Objective
Bipolar
disorder
typically
features
episodes
of
mania
and
depression,
frequently
accompanied
by
psychosis.
While
progress
has
been
made
in
understanding
the
genetics
depression
psychosis,
remains
underexplored.
Methods
We
employed
Genomic
Structural
Equation
Modeling
to
subtract
genetic
effects
schizophrenia
major
depressive
(MDD)
from
bipolar
identify
a
trait
specific
mania.
Results
The
SEM
model
revealed
significant
loadings
for
“mania”
(0.67,
p<0.001),
“psychosis”
(0.58,
“depression”
(0.29,
p<0.001)
factors,
with
mania,
MDD
explaining
45%,
8%
34%
variance
disorder,
respectively.
Seven
genomic
regions
associated
were
identified.
Key
include
rs9834970
(3q12.1,
previously
lithium
response),
rs6992333
(8q13.1,
brain
structure),
rs12206087
(6q14.3,
intelligence
cortical
surface).
Additionally,
exhibited
distinct
correlations
compared
across
psychiatric,
substance
abuse,
somatic,
social,
neurological
traits,
including
significantly
higher
(r
g
=0.08
vs
−0.07)
educational
attainment
=0.17
0.12),
an
unexpected
reduced
correlation
risky
sexual
behavior
=0.14
0.27).
Conclusions
These
findings
enhance
disorder’s
architecture,
potentially
offering
more
disorder-specific
GWAS.
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 27, 2024
Abstract
Background
Previous
studies
have
demonstrated
a
causal
relationship
between
gut
microbiota/structural
connectivity
and
psoriasis.
However,
it
is
not
clear
whether
structural
act
as
mediator
in
the
pathway
from
microbiota
to
Methods
Based
on
genome-wide
association
(GWAS),
we
performed
two-step
MR-analysis
order
examine
role
of
(N
=
26,333)
potential
mediators
13,266)
psoriasis
15,967).
Summary
statistics
for
were
sourced
MiBioGen
consortium,
while
data
came
GWAS
catalog.
Results
Through
MR
analysis,
identified
2
15
inflammatory
proteins
related
such
genus
Coprococcus3
LH
Limbic
caudate
(OR
1.33,
95%
CI:
1.00–1.76,
P
0.048;
OR
0.70,
0.56–0.86,
0.001).
After
MVMR
remained
significant
relation
decreased
risk
(P
0.0005)
was
no
longer
0.121).
The
mediating
effect
calculated
0.047
1.049,
1.006–1.109)
accounting
16.6%
total
effect.
Conclusion
Our
study
provides
genetic
evidence
that
psoriasis,
mediators.
Brain Sciences,
Год журнала:
2024,
Номер
14(10), С. 1030 - 1030
Опубликована: Окт. 17, 2024
Glaucoma
is
a
neurodegenerative
ocular
disease
that
accompanied
by
cerebral
damage
extending
beyond
the
visual
system.
Recent
studies
based
on
diffusion
tensor
tractography
have
suggested
an
association
between
glaucoma
and
brain
structural
connectivity
but
not
clarified
causality.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 21, 2024
Abstract
The
genetic
architecture
of
human
brain
networks
is
central
to
understanding
the
organization
and
evolution
cortex,
causal
relationships
between
structure
function,
pathogenesis
heritable
neuropsychiatric
disorders.
However,
current
genetics
remains
fragmented.
Here,
we
investigated
common
effects
on
Morphometric
INverse
Divergence
(MIND),
a
biologically-validated,
heritable,
multimodal
MRI
metric
inter-areal
similarity
connectivity.
Using
discovery
dataset
(N
>
30,000
adults),
estimated
subject-specific
MIND
from
multivariate
distributions
four
features
at
each
23
cortical
areas
performed
genome-wide
association
studies
(GWAS)
276
edges.
These
edge-level
were
highly
replicated
by
parallel
GWAS
an
independent
validation
18,000
adults).
We
found
that
strong
correlations
multiple
edges
largely
reducible
two
gradients
genetically-determined
similarity,
which
was
aligned
with
geodesic
distance
one
phylogenetically
primitive
(paleocortex
archicortex)
predicted
dual
origin
theory
evolution.
Genetic
more
than
comparable
derived
functional
connectivity
networks;
paleocortical
trend
genetically
correlated
with,
causally
predictive
of,
Finally,
identified
global
local
both
nine
clinical
diagnoses
or
biomedical
traits,
indicating
normative
pleiotropically
associated
inherited
risk
disorders
systemic
metabolic
immune
traits.
results
provide
fresh
insight
into
origins
cortex
their
implications
for
function
health.
