bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Aug. 17, 2022
Abstract
Elevated
intraocular
pressure
(IOP)
is
influenced
by
environmental
and
genetic
factors.
Increased
IOP
a
major
risk
factor
for
most
types
of
glaucoma,
including
primary
open
angle
glaucoma
(POAG).
Investigating
the
basis
may
lead
to
better
understanding
molecular
mechanisms
POAG.
The
goal
this
study
was
identify
loci
involved
in
regulating
using
outbred
heterogeneous
stock
(HS)
rats.
HS
rats
are
multigenerational
population
derived
from
eight
inbred
strains
that
have
been
fully
sequenced.
This
ideal
genome-wide
association
studies
(GWASs)
owing
accumulated
recombinations
among
well-defined
haplotypes,
relatively
high
allele
frequencies,
accessibility
large
collection
tissue
samples,
allelic
effect
size
compared
human
studies.
Both
male
female
(N=1,812)
were
used
study.
Genotyping-by-sequencing
obtain
~3.5
million
single
nucleotide
polymorphisms
(SNP)
each
individual.
SNP
heritability
0.32,
which
agrees
with
other
We
performed
GWAS
phenotype
linear
mixed
model
permutation
determine
significance
threshold.
identified
three
significant
on
chromosomes
1,
5,
16.
Next,
we
sequenced
mRNA
51
whole
eye
samples
find
cis-eQTLs
aid
identification
candidate
genes.
report
5
genes
within
those
loci:
Tyr
,
Ctsc
Plekhf2
Ndufaf6
Angpt2
.
previously
implicated
IOP-related
conditions.
represent
novel
findings
provide
new
insight
into
IOP.
highlights
efficacy
investigating
genetics
elevated
identifying
potential
future
functional
testing.
Contribution
field
statement
Glaucoma
leading
cause
irreversible
blindness
worldwide.
Intraocular
only
known
modifiable
factor.
describes
results
(GWAS)
identifies
regulation.
To
our
knowledge,
first
rat
model.
Identifying
provides
factors
humans
pharmacological
targets
advantageous
studying
natural
variations
IOP,
controlling
exposures,
providing
easier
access
can
be
phenotyping
gene
expression
Genes,
Journal Year:
2024,
Volume and Issue:
15(2), P. 161 - 161
Published: Jan. 26, 2024
The
phenotypic
similarities
between
exfoliation
syndrome
(XFS)/exfoliation
glaucoma
(XFG)
and
pigment
dispersion
(PDS)/pigmentary
(PG),
particularly
their
association
with
material
deposition
in
the
eye's
anterior
segment,
have
prompted
investigations
into
genetic
commonalities.
This
study
focuses
on
LOXL1
gene,
conducting
a
comprehensive
meta-analysis
of
three
candidate
gene
studies.
We
analyzed
single
nucleotide
polymorphisms
(SNPs)
LOXL1:
rs1048661,
rs3825942,
rs2165241.
Our
results
reveal
nominal
significance
for
exonic
SNPs
rs1048661
rs3825942
(p
≤
0.01),
but
show
no
significant
intronic
SNP
rs2165241
=
0.83)
PDS/PG.
There
was
homogeneity
across
cohorts
(I2
0),
sensitivity
analyses
funnel
plots
confirmed
lower
likelihood
bias
our
findings.
lack
statistically
variants
PDS/PG
at
p
<
0.05
attributable
to
insufficient
statistical
power
pooled
data,
which
ranged
from
5%
37%
SNPs.
suggests
Further
validation
exploration
XFS/XFG-associated
genes
larger
more
diverse
would
be
helpful
determine
correlation
or
distinctiveness
these
conditions.
RESEARCH RESULTS IN BIOMEDICINE,
Journal Year:
2024,
Volume and Issue:
10(1), P. 23 - 52
Published: March 30, 2024
Background:
Mendelian
randomization
(MR)
is
an
analytic
approach
in
genetic
epidemiology
which
uses
the
results
of
genome-wide
association
studies
(GWAS)
to
assess
causal
relationships
between
various
risk
factors
and
phenotypes
interest
(or
diseases)
ophthalmology.
The
aim
study:
To
describe
current
opportunities
for
use
MR
ophthalmic
research.
Materials
methods:
We
searched
Scopus,
Medline
Web
Science
journals
up
August
2022
using
PRISMA
protocol
“Preferred
Reporting
Items
Systematic
Review
Meta-Analysis”.
following
information
was
extracted:
identified
factor(s)
disease(s),
design
study,
sensitivity
analysis(es)
performed
if
any,
instrument(s)
used,
also
whether
relationship
outcome
confirmed
by
study.
Results:
review
included
a
total
37
publications
that
tested
211
associations
factor
with
disease.
articles
were
published
peer-reviewed
25
them
(67,5%)
2020
or
later.
method
indicated
role
blood
serum
lipids,
C-reactive
protein,
free
thyroxine,
smoking
alcohol
intake
development
age-related
macular
degeneration.
For
glaucoma,
type
2
diabetes,
glucose,
refractive
abnormalities,
elevated
intraocular
pressure
have
been
shown
be
significant.
analysis
revealed
pressure,
level
education,
body
weight
at
birth
errors.
hypertension
cataracts
determined
method.
Conclusion:
97
analyses
ophthalmology
significant
number
eye
diseases,
will
serve
as
guideline
clinical
trials
drug
development.
Clinical Epigenetics,
Journal Year:
2024,
Volume and Issue:
16(1)
Published: Nov. 13, 2024
This
study
aimed
to
identify
DNA
methylation
biomarkers
associated
with
myopia
using
summary-data-based
Mendelian
randomization
(SMR).
A
systematic
search
of
the
PubMed,
Web
Science,
Cochrane
Library,
and
Embase
databases
was
conducted
up
March
27,
2024.
SMR
analyses
were
performed
integrate
genome-wide
association
(GWAS)
quantitative
trait
loci
(mQTL)
expression
(eQTL)
studies.
The
heterogeneity
in
dependent
instrument
(HEIDI)
test
utilized
distinguish
pleiotropic
associations
from
linkage
disequilibrium.
review
identified
26
five
studies,
no
overlap
observed
among
those
by
different
After
integrating
GWAS
multi-omics
data
mQTL
eQTL,
six
genes
significantly
myopia:
PRMT6
(cg00944433
cg15468180),
SH3YL1
(cg03299269,
cg11361895,
cg13354988),
ZKSCAN4
(cg01192291),
GATS
(cg17830204),
NPAT
(cg04826772),
UBE2I
(cg03545757
cg08025960).
We
risk
that
may
be
helpful
elucidate
etiology
mechanisms
myopia.
Further
experimental
validation
studies
are
required
corroborate
these
findings.
Human Genomics,
Journal Year:
2024,
Volume and Issue:
18(1)
Published: April 17, 2024
Age-related
cataract
and
hearing
difficulties
are
major
sensory
disorders
that
often
co-exist
in
the
global-wide
elderly
have
a
tangible
influence
on
quality
of
life.
However,
epidemiologic
association
between
remains
unexplored,
while
little
is
known
about
whether
two
share
their
genetic
etiology.
We
first
investigated
clinical
using
UK
Biobank
covering
502,543
individuals.
Both
unmatched
analysis
(adjusted
for
confounders)
matched
(one
control
each
patient
with
according
to
confounding
factors)
were
undertaken
confirmed
was
associated
(OR,
2.12;
95%
CI,
1.98-2.27;
OR,
2.03;
1.86-2.23,
respectively).
Furthermore,
we
explored
quantified
shared
architecture
these
complex
at
common
variant
level
bivariate
causal
mixture
model
(MiXeR)
conditional/conjunctional
false
discovery
rate
method
based
largest
available
genome-wide
studies
(N
=
585,243)
323,978).
Despite
detecting
only
negligible
correlation,
observe
polygenic
overlap
identify
6
loci
mixed
directions
effects.
Follow-up
implicates
candidate
genes
QKI,
STK17A,
TYR,
NSF,
TCF4
likely
contribute
pathophysiology
cataracts
difficulties.
In
conclusion,
this
study
demonstrates
presence
provides
new
insights
into
level.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Aug. 17, 2022
Abstract
Elevated
intraocular
pressure
(IOP)
is
influenced
by
environmental
and
genetic
factors.
Increased
IOP
a
major
risk
factor
for
most
types
of
glaucoma,
including
primary
open
angle
glaucoma
(POAG).
Investigating
the
basis
may
lead
to
better
understanding
molecular
mechanisms
POAG.
The
goal
this
study
was
identify
loci
involved
in
regulating
using
outbred
heterogeneous
stock
(HS)
rats.
HS
rats
are
multigenerational
population
derived
from
eight
inbred
strains
that
have
been
fully
sequenced.
This
ideal
genome-wide
association
studies
(GWASs)
owing
accumulated
recombinations
among
well-defined
haplotypes,
relatively
high
allele
frequencies,
accessibility
large
collection
tissue
samples,
allelic
effect
size
compared
human
studies.
Both
male
female
(N=1,812)
were
used
study.
Genotyping-by-sequencing
obtain
~3.5
million
single
nucleotide
polymorphisms
(SNP)
each
individual.
SNP
heritability
0.32,
which
agrees
with
other
We
performed
GWAS
phenotype
linear
mixed
model
permutation
determine
significance
threshold.
identified
three
significant
on
chromosomes
1,
5,
16.
Next,
we
sequenced
mRNA
51
whole
eye
samples
find
cis-eQTLs
aid
identification
candidate
genes.
report
5
genes
within
those
loci:
Tyr
,
Ctsc
Plekhf2
Ndufaf6
Angpt2
.
previously
implicated
IOP-related
conditions.
represent
novel
findings
provide
new
insight
into
IOP.
highlights
efficacy
investigating
genetics
elevated
identifying
potential
future
functional
testing.
Contribution
field
statement
Glaucoma
leading
cause
irreversible
blindness
worldwide.
Intraocular
only
known
modifiable
factor.
describes
results
(GWAS)
identifies
regulation.
To
our
knowledge,
first
rat
model.
Identifying
provides
factors
humans
pharmacological
targets
advantageous
studying
natural
variations
IOP,
controlling
exposures,
providing
easier
access
can
be
phenotyping
gene
expression
