medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Фев. 26, 2023
Polygenic
risk
scores
(PRS)
are
an
emerging
tool
to
predict
the
clinical
phenotypes
and
outcomes
of
individuals.
Validation
transferability
existing
PRS
across
independent
datasets
diverse
ancestries
limited,
which
hinders
practical
utility
exacerbates
health
disparities.
We
propose
PRSmix,
a
framework
that
evaluates
leverages
corpus
target
trait
improve
prediction
accuracy,
PRSmix+,
incorporates
genetically
correlated
traits
better
capture
human
genetic
architecture.
applied
PRSmix
47
32
diseases/traits
in
European
South
Asian
ancestries,
respectively.
demonstrated
mean
accuracy
improvement
1.20-fold
(95%
CI:
[1.10;
1.3];
P-value
=
9.17
×
10
Cell Genomics,
Год журнала:
2024,
Номер
4(4), С. 100523 - 100523
Опубликована: Март 19, 2024
Polygenic
risk
scores
(PRSs)
are
an
emerging
tool
to
predict
the
clinical
phenotypes
and
outcomes
of
individuals.
We
propose
PRSmix,
a
framework
that
leverages
PRS
corpus
target
trait
improve
prediction
accuracy,
PRSmix+,
which
incorporates
genetically
correlated
traits
better
capture
human
genetic
architecture
for
47
32
diseases/traits
in
European
South
Asian
ancestries,
respectively.
PRSmix
demonstrated
mean
accuracy
improvement
1.20-fold
(95%
confidence
interval
[CI],
[1.10;
1.3];
p
=
9.17
×
10
European Heart Journal,
Год журнала:
2023,
Номер
44(36), С. 3456 - 3465
Опубликована: Май 31, 2023
Abstract
Aims
Complications
of
coronary
artery
disease
(CAD)
represent
the
leading
cause
death
among
adults
globally.
This
study
examined
associations
and
clinical
utilities
genetic,
sociodemographic,
lifestyle,
risk
factors
on
CAD
recurrence.
Methods
results
Data
were
from
7024
UK
Biobank
middle-aged
with
established
at
enrolment.
Cox
proportional
hazards
regressions
modelled
age
enrolment,
first
diagnosis,
sex,
cigarette
smoking,
physical
activity,
diet,
sleep,
Townsend
Deprivation
Index,
body
mass
index,
blood
pressure,
lipids,
glucose,
lipoprotein(a),
C
reactive
protein,
estimated
glomerular
filtration
rate
(eGFR),
statin
prescription,
polygenic
score
(PRS)
post-enrolment
Over
a
median
[interquartile
range]
follow-up
11.6
[7.2–12.7]
years,
2003
(28.5%)
recurrent
events
occurred.
The
hazard
ratio
(95%
confidence
interval
[CI])
for
recurrence
was
most
pronounced
current
smoking
(1.35,
1.13–1.61)
per
standard
deviation
increase
in
(0.74,
0.67–0.82).
Additionally,
PRS,
C-reactive
low-density
lipoprotein
cholesterol,
deprivation,
sleep
quality,
eGFR,
high-density
(HDL)
cholesterol
also
significantly
associated
risk.
Based
indices
CI),
strongest
predictors
PRS
(0.58,
0.57–0.59),
HDL
(0.57,
0.57–0.58),
initial
event
0.56–0.57).
In
addition
to
traditional
factors,
comprehensive
model
improved
index
0.644
(0.632–0.654)
0.676
(0.667–0.686).
Conclusion
Sociodemographic,
clinical,
laboratory
are
each
genetic
risk,
event,
concentration
explaining
most.
Journal of the American College of Cardiology,
Год журнала:
2023,
Номер
82(13), С. 1343 - 1359
Опубликована: Сен. 1, 2023
Reducing
the
incidence
and
prevalence
of
standard
modifiable
cardiovascular
risk
factors
(SMuRFs)
is
critical
to
tackling
global
burden
coronary
artery
disease
(CAD).
However,
a
substantial
number
individuals
develop
atherosclerosis
despite
no
SMuRFs.
SMuRFless
patients
presenting
with
myocardial
infarction
have
been
observed
an
unexpected
higher
early
mortality
compared
their
counterparts
at
least
1
SMuRF.
Evidence
for
optimal
management
these
lacking.
We
assembled
international,
multidisciplinary
team
evidence-based
clinical
pathway
CAD
patients.
A
modified
Delphi
method
was
applied.
The
resulting
confirms
underlying
true
status,
ensures
secondary
prevention,
considers
additional
tests
interventions
less
typical
contributors.
This
dedicated
previously
overlooked
population,
accompanying
registry,
aims
improve
outcomes
through
enhanced
adherence
prevention
diagnosis
observed.
The American Journal of Human Genetics,
Год журнала:
2023,
Номер
110(5), С. 722 - 740
Опубликована: Апрель 14, 2023
Coronary
artery
disease
(CAD)
is
a
pandemic
where
up
to
half
of
the
risk
explained
by
genetic
factors.
Advanced
insights
into
basis
CAD
require
deeper
understanding
contributions
different
cell
types,
molecular
pathways,
and
genes
heritability.
Here,
we
investigate
biological
diversity
atherosclerosis-associated
states
interrogate
their
contribution
using
single-cell
bulk
RNA
sequencing
(RNA-seq)
mouse
human
lesions.
We
identified
12
disease-associated
that
characterized
further
gene
set
functional
profiling,
ligand-receptor
prediction,
transcription
factor
inference.
Importantly,
Vcam1+
smooth
muscle
state
contributed
most
SNP-based
heritability
CAD.
In
line
with
this,
variants
near
regulatory
elements
largest
fraction
CAD-risk
variance
between
individuals.
Using
this
information
for
variant
prioritization,
derived
hybrid
polygenic
score
(PRS)
demonstrated
improved
performance
over
classical
PRS.
Our
results
provide
mechanisms
associated
risk,
which
could
make
promising
precision
medicine
tailored
therapeutic
interventions
in
future.
