bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 15, 2024
Abstract
Background
Heterozygous
variants
in
GBA1
are
the
commonest
genetic
risk
factor
for
Parkinson
disease
(PD)
but
penetrance
is
incomplete.
dysfunction
can
cause
gastrointestinal
disturbances
and
microbiome
changes
preclinical
models.
Mounting
evidence
suggests
that
microbiota-gut-brain
axis
potentially
implicated
PD
pathogenesis.
Whether
gut
composition
influenced
by
host
genetics
heterozygosis
has
never
been
explored.
Objectives
To
evaluate
whether
heterozygosity
pathogenic
L444P
variant
perturbations
composition.
Methods
Faecal
samples
collected
from
L444P/WT
WT/WT
mice
at
3
6
months
of
age
were
analysed
through
shotgun
metagenomic
sequencing.
Results
No
differences
α-
β-diversity
detected
between
genotyped
groups,
either
time
points.
Overall,
we
found
a
little
variation
functional
potential
over
time.
Conclusion
Host
genotype
does
not
impact
structure
presented
mouse
model.
Studies
investigating
effect
second
hit
on
physiology
could
explain
partial
PD.
PLoS ONE,
Journal Year:
2024,
Volume and Issue:
19(11), P. e0313631 - e0313631
Published: Nov. 15, 2024
Background
Parkinson’s
disease
(PD)
is
a
neurodegenerative
disorder,
primarily
characterized
by
motor
impairments.
Vitamin
D
has
several
regulatory
functions
in
nerve
cell
survival
and
gene
expression
via
its
receptors.
Although
research
shown
that
vitamin
deficiency
prevalent
among
PD
patients,
the
causal
link
to
risk
remains
unclear.
This
study
aims
investigate
relationship
between
using
bidirectional
two-sample
Mendelian
randomization
(MR)
analysis
method.
Methods
applied
MR
explore
PD.
We
selected
statistically
significant
single
nucleotide
polymorphisms
(SNPs)
related
25-hydroxyvitamin
(25(OH)D)
as
instrumental
variables
(IVs),
ensuring
no
association
with
known
confounders.
The
used
GWAS
data
from
over
1.2
million
Europeans
across
four
major
published
datasets,
elucidating
genetic
correlation
levels
Results
identified
148
SNPs
associated
25(OH)D.
After
adjustment
for
confounding-related
SNPs,
131
remained
analysis.
Data
three
cohorts
revealed
25(OH)D
IVW
method
(
P
cohort1
=
0.365,
cohort2
0.525,
cohort3
0.117).
reverse
indicated
insufficient
evidence
of
causing
decreased
0.776).
Conclusion
first
use
results
indicate
are
not
significantly
causally
at
level.
Therefore,
future
studies
should
exercise
caution
when
investigating
risk.
While
direct
exists
PD,
this
does
preclude
potential
biomarker
diagnosis.
Furthermore,
larger-scale
longitudinal
necessary
evaluate
diagnostic
predictive
value
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 15, 2024
Abstract
Background
Heterozygous
variants
in
GBA1
are
the
commonest
genetic
risk
factor
for
Parkinson
disease
(PD)
but
penetrance
is
incomplete.
dysfunction
can
cause
gastrointestinal
disturbances
and
microbiome
changes
preclinical
models.
Mounting
evidence
suggests
that
microbiota-gut-brain
axis
potentially
implicated
PD
pathogenesis.
Whether
gut
composition
influenced
by
host
genetics
heterozygosis
has
never
been
explored.
Objectives
To
evaluate
whether
heterozygosity
pathogenic
L444P
variant
perturbations
composition.
Methods
Faecal
samples
collected
from
L444P/WT
WT/WT
mice
at
3
6
months
of
age
were
analysed
through
shotgun
metagenomic
sequencing.
Results
No
differences
α-
β-diversity
detected
between
genotyped
groups,
either
time
points.
Overall,
we
found
a
little
variation
functional
potential
over
time.
Conclusion
Host
genotype
does
not
impact
structure
presented
mouse
model.
Studies
investigating
effect
second
hit
on
physiology
could
explain
partial
PD.
