Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Aug. 17, 2023
Genome-wide
association
studies
(GWAS)
have
linked
hundreds
of
loci
to
cardiac
diseases.
However,
in
most
the
causal
variants
and
their
target
genes
remain
unknown.
We
developed
a
combined
experimental
analytical
approach
that
integrates
single
cell
epigenomics
with
GWAS
prioritize
risk
genes.
profiled
accessible
chromatin
cells
obtained
from
human
hearts
leveraged
data
study
genetics
Atrial
Fibrillation
(AF),
common
arrhythmia.
Enrichment
analysis
AF
using
cell-type-resolved
open
regions
(OCRs)
implicated
cardiomyocytes
as
main
mediator
risk.
then
performed
statistical
fine-mapping,
leveraging
information
OCRs,
identified
putative
122
AF-associated
loci.
Taking
advantage
fine-mapping
results,
our
novel
procedure
for
gene
discovery
prioritized
46
high-confidence
genes,
highlighting
transcription
factors
signal
transduction
pathways
important
heart
development.
In
summary,
provides
comprehensive
map
general
framework
integrate
single-cell
genomics
genetic
complex
traits.
PLoS Genetics,
Journal Year:
2022,
Volume and Issue:
18(7), P. e1010299 - e1010299
Published: July 19, 2022
In
recent
work,
Wang
et
al
introduced
the
"Sum
of
Single
Effects"
(SuSiE)
model,
and
showed
that
it
provides
a
simple
efficient
approach
to
fine-mapping
genetic
variants
from
individual-level
data.
Here
we
present
new
methods
for
fitting
SuSiE
model
summary
data,
example
single-SNP
z-scores
an
association
study
linkage
disequilibrium
(LD)
values
estimated
suitable
reference
panel.
To
develop
these
methods,
first
describe
simple,
generic
strategy
extending
any
data
method
deal
with
The
key
idea
is
replace
usual
regression
likelihood
analogous
based
on
We
show
existing
such
as
FINEMAP
CAVIAR
also
(implicitly)
use
this
strategy,
but
in
different
ways,
so
common
framework
understanding
fine-mapping.
investigate
other
practical
issues
including
problems
caused
by
inconsistencies
between
LD
estimates,
diagnostics
identify
inconsistencies.
refinement
procedure
improves
fits
some
sets,
hence
overall
reliability
results.
Detailed
evaluations
range
simulated
sets
applied
competitive,
both
speed
accuracy,
best
available
Nature,
Journal Year:
2023,
Volume and Issue:
620(7975), P. 839 - 848
Published: Aug. 16, 2023
Abstract
Mitochondrial
DNA
(mtDNA)
is
a
maternally
inherited,
high-copy-number
genome
required
for
oxidative
phosphorylation
1
.
Heteroplasmy
refers
to
the
presence
of
mixture
mtDNA
alleles
in
an
individual
and
has
been
associated
with
disease
ageing.
Mechanisms
underlying
common
variation
human
heteroplasmy,
influence
nuclear
on
this
variation,
remain
insufficiently
explored.
Here
we
quantify
copy
number
(mtCN)
heteroplasmy
using
blood-derived
whole-genome
sequences
from
274,832
individuals
perform
genome-wide
association
studies
identify
loci.
Following
blood
cell
composition
correction,
find
that
mtCN
declines
linearly
age
variants
at
92
We
observe
nearly
everyone
harbours
heteroplasmic
obeying
two
principles:
(1)
single
nucleotide
tend
arise
somatically
accumulate
sharply
after
70
years,
whereas
(2)
indels
are
inherited
as
mixtures
relative
levels
42
loci
involved
replication,
maintenance
novel
pathways.
These
may
act
by
conferring
replicative
advantage
certain
alleles.
As
illustrative
example,
length
variant
carried
more
than
50%
humans
position
chrM:302
within
G-quadruplex
previously
proposed
mediate
transcription/replication
switching
2,3
exerts
cis
-acting
genetic
control
over
abundance
itself
in-
trans
encoding
machinery
regulatory
switch.
Our
study
suggests
can
shape
dynamics
across
population.
Nature Genetics,
Journal Year:
2024,
Volume and Issue:
56(2), P. 222 - 233
Published: Jan. 4, 2024
Abstract
Most
genome-wide
association
studies
(GWAS)
of
major
depression
(MD)
have
been
conducted
in
samples
European
ancestry.
Here
we
report
a
multi-ancestry
GWAS
MD,
adding
data
from
21
cohorts
with
88,316
MD
cases
and
902,757
controls
to
previously
reported
data.
This
analysis
used
range
measures
define
included
African
(36%
effective
sample
size),
East
Asian
(26%)
South
(6%)
ancestry
Hispanic/Latin
American
participants
(32%).
The
identified
53
significantly
associated
novel
loci.
For
loci
samples,
fewer
than
expected
were
transferable
other
groups.
Fine
mapping
benefited
additional
diversity.
A
transcriptome-wide
study
205
genes.
These
findings
suggest
that,
for
increasing
ancestral
global
diversity
genetic
may
be
particularly
important
ensure
discovery
core
genes
inform
about
transferability
findings.
Human Genomics,
Journal Year:
2025,
Volume and Issue:
19(1)
Published: Jan. 31, 2025
Non-communicable
diseases
(NCDs)
such
as
cardiovascular
diseases,
chronic
respiratory
cancers,
diabetes,
and
mental
health
disorders
pose
a
significant
global
challenge,
accounting
for
the
majority
of
fatalities
disability-adjusted
life
years
worldwide.
These
arise
from
complex
interactions
between
genetic,
behavioral,
environmental
factors,
necessitating
thorough
understanding
these
dynamics
to
identify
effective
diagnostic
strategies
interventions.
Although
recent
advances
in
multi-omics
technologies
have
greatly
enhanced
our
ability
explore
interactions,
several
challenges
remain.
include
inherent
complexity
heterogeneity
multi-omic
datasets,
limitations
analytical
approaches,
severe
underrepresentation
non-European
genetic
ancestries
most
omics
which
restricts
generalizability
findings
exacerbates
disparities.
This
scoping
review
evaluates
landscape
data
related
NCDs
2000
2024,
focusing
on
advancements
integration,
translational
applications,
equity
considerations.
We
highlight
need
standardized
protocols,
harmonized
data-sharing
policies,
advanced
approaches
artificial
intelligence/machine
learning
integrate
study
gene-environment
interactions.
also
opportunities
translating
insights
(GxE)
research
into
precision
medicine
strategies.
underscore
potential
advancing
enhancing
patient
outcomes
across
diverse
underserved
populations,
emphasizing
fairness-centered
strategic
investments
build
local
capacities
underrepresented
populations
regions.
