Variables associated with cognitive function: an exposome-wide and mendelian randomization analysis
Alzheimer s Research & Therapy,
Год журнала:
2025,
Номер
17(1)
Опубликована: Янв. 7, 2025
Evidence
indicates
that
cognitive
function
is
influenced
by
potential
environmental
factors.
We
aimed
to
determine
the
variables
influencing
function.
Our
study
included
164,463
non-demented
adults
(89,644
[54.51%]
female;
mean
[SD]
age,
56.69
[8.14]
years)
from
UK
Biobank
who
completed
four
assessments
at
baseline.
364
were
finally
extracted
for
analysis
through
a
rigorous
screening
process.
performed
univariate
analyses
identify
significantly
associated
with
each
in
two
equal-sized
split
discovery
and
replication
datasets.
Subsequently,
identified
further
assessed
multivariable
model.
Additionally,
model,
we
explored
associations
longitudinal
decline.
Moreover,
one-
two-
sample
Mendelian
randomization
(MR)
conducted
confirm
genetic
associations.
Finally,
quality
of
pooled
evidence
between
was
evaluated.
252
(69%)
exhibited
significant
least
one
dataset.
Of
these,
231
(92%)
successfully
replicated.
our
41
function,
spanning
categories
such
as
education,
socioeconomic
status,
lifestyle
factors,
body
measurements,
mental
health,
medical
conditions,
early
life
household
characteristics.
Among
these
variables,
12
more
than
domain,
all
subgroup
analyses.
And
LASSO,
rigde,
principal
component
indicated
robustness
primary
results.
among
Furthermore,
22
supported
one-sample
MR
analysis,
5
confirmed
two-sample
analysis.
10
rated
high.
Based
on
adopting
favorable
38%
34%
decreased
risks
dementia
Alzheimer's
disease
(AD).
Overall,
constructed
an
database
which
could
contribute
prevention
impairment
dementia.
Язык: Английский
Causal modeling of gene effects from regulators to programs to traits: integration of genetic associations and Perturb-seq
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 24, 2025
Genetic
association
studies
provide
a
unique
tool
for
identifying
causal
links
from
genes
to
human
traits
and
diseases.
However,
it
is
challenging
determine
the
biological
mechanisms
underlying
most
associations,
we
lack
genome-scale
approaches
inferring
mechanistic
pathways
cellular
functions
traits.
Here
propose
new
bridge
this
gap
by
combining
quantitative
estimates
of
gene-trait
relationships
loss-of-function
burden
tests
with
gene-regulatory
connections
inferred
Perturb-seq
experiments
in
relevant
cell
types.
By
these
two
forms
data,
aim
build
graphs
which
directional
associations
trait
can
be
explained
their
regulatory
effects
on
programs
or
direct
trait.
As
proof-of-concept,
constructed
graph
gene
hierarchy
that
jointly
controls
three
partially
co-regulated
blood
We
perturbation
trait-relevant
types,
coupled
gene-level
effect
sizes
traits,
between
genetics
biology.
Язык: Английский
Transforming cancer treatment: integrating patient-derived organoids and CRISPR screening for precision medicine
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Март 25, 2025
The
persistently
high
mortality
rates
associated
with
cancer
underscore
the
imperative
need
for
innovative,
efficacious,
and
safer
therapeutic
agents,
as
well
a
more
nuanced
understanding
of
tumor
biology.
Patient-derived
organoids
(PDOs)
have
emerged
innovative
preclinical
models
significant
translational
potential,
capable
accurately
recapitulating
structural,
functional,
heterogeneous
characteristics
primary
tumors.
When
integrated
cutting-edge
genomic
tools
such
CRISPR,
PDOs
provide
powerful
platform
identifying
driver
genes
novel
targets.
This
comprehensive
review
delves
into
recent
advancements
in
CRISPR-mediated
functional
screens
leveraging
across
diverse
types,
highlighting
their
pivotal
role
high-throughput
genomics
microenvironment
(TME)
modeling.
Furthermore,
this
highlights
synergistic
potential
integrating
CRISPR
immunotherapy,
focusing
on
uncovering
immune
evasion
mechanisms
improving
efficacy
immunotherapeutic
approaches.
Together,
these
technologies
offer
promise
advancing
precision
oncology.
Язык: Английский
Specificity, length, and luck: How genes are prioritized by rare and common variant association studies
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 16, 2024
Standard
genome-wide
association
studies
(GWAS)
and
rare
variant
burden
tests
are
essential
tools
for
identifying
trait-relevant
genes.
Although
these
methods
conceptually
similar,
we
show
by
analyzing
of
209
quantitative
traits
in
the
UK
Biobank
that
they
systematically
prioritize
different
This
raises
question
how
genes
should
ideally
be
prioritized.
We
propose
two
prioritization
criteria:
1)
trait
importance
-
much
a
gene
quantitatively
affects
trait;
2)
specificity
gene's
under
study
relative
to
its
across
all
traits.
find
GWAS
near
trait-specific
variants
,
while
.
Because
non-coding
can
context
specific,
highly
pleiotropic
genes,
generally
cannot.
Both
designs
also
affected
distinct
trait-irrelevant
factors,
complicating
their
interpretation.
Our
results
illustrate
reveal
aspects
biology
suggest
ways
improve
interpretation
usage.
Язык: Английский