Nature Genetics,
Journal Year:
2022,
Volume and Issue:
54(9), P. 1305 - 1319
Published: Aug. 18, 2022
Abstract
To
capture
the
full
spectrum
of
genetic
risk
for
autism,
we
performed
a
two-stage
analysis
rare
de
novo
and
inherited
coding
variants
in
42,607
autism
cases,
including
35,130
new
cases
recruited
online
by
SPARK.
We
identified
60
genes
with
exome-wide
significance
(
P
<
2.5
×
10
−6
),
five
NAV3
,
ITSN1
MARK2
SCAF1
HNRNPUL2
).
The
association
is
primarily
driven
loss-of-function
(LoF)
variants,
an
estimated
relative
4,
consistent
moderate
effect.
Autistic
individuals
LoF
four
moderate-risk
;
n
=
95)
have
less
cognitive
impairment
than
129
autistic
highly
penetrant
CHD8,
SCN2A,
ADNP,
FOXP1
SHANK3
)
(59%
vs
88%,
1.9
Power
calculations
suggest
that
much
larger
numbers
are
needed
to
identify
additional
genes.
Frontiers in Neuroscience,
Journal Year:
2017,
Volume and Issue:
11
Published: Sept. 15, 2017
Humans
evolved
within
a
microbial
ecosystem
resulting
in
an
interlinked
physiology.
The
gut
microbiota
can
signal
to
the
brain
via
immune
system,
vagus
nerve
or
other
host-microbe
interactions
facilitated
by
hormones,
regulation
of
tryptophan
metabolism
and
metabolites
such
as
short
chain
fatty
acids
(SCFA),
influence
development,
function
behaviour.
Emerging
evidence
suggests
that
may
play
role
shaping
cognitive
networks
encompassing
emotional
social
domains
neurodevelopmental
disorders.
Drawing
upon
preclinical
clinical
evidence,
we
review
potential
origins
development
related
Autism
spectrum
disorders
(ASD)
Schizophrenia.
Small
preliminary
studies
have
demonstrated
alterations
both
ASD
Schizophrenia
compared
healthy
controls.
However,
await
further
mechanistic
insights,
together
with
large
scale
longitudinal
trials,
encompass
systems
level
dimensional
approach,
investigate
whether
promising
pre-clinical
initial
findings
lead
relevance.
