Research Square (Research Square),
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 21, 2025
Abstract
Our
understanding
of
the
influence
ancestral
background
on
genetically
determined
expression
remains
limited,
especially
when
gene
models
are
applied
to
studies
from
different
or
multiple
populations.
We
performed
transcriptome
wide
association
(TWAS)
in
6
psychiatric
conditions,
leveraging
trained
cohorts
with
proportions
African,
European,
and
Indigenous
American
genetic
ancestries.
For
comparison
we
repeated
each
TWAS
using
a
model
individuals
predominantly
European
ancestry.
identified
1,416
statistically
significant
associations
(FDR
p
<
0.05)
across
diagnoses,
which
62%
were
uniquely
detected
by
admixed
models.
observed
>
92%
correlation
gene-level
effects
disease
risk,
statistic
that
remained
robust
for
results
only
reached
statistical
significance
one
population.
Using
validated
greatly
extended
yield
TWAS.
The
resulting
transcriptomic
signatures
implicated
neuroimaging
features
associated
diagnostic
symptoms.
