NEUROGENETICS & PSYCHIATRIC DISORDERS: Neurodevelopmental and Neurological Disorders
Group
Professor Anthony P. Monaco
- Group Head
"Gene-gene and gene-environment interactions
underlying speech, language and reading
development"
1.1 Sample:
The
sample to be used in this project comes from the
Avon Longitudinal Study
of Parents and Children (ALSPAC)
ALSPAC
is a large epidemiological sample.
It is characterised by
comprehensive longitudinal records of the pregnancies and
deliveries, socio-economical and medical conditions, assessments
on a wide range of physical, behavioural and neuropsychological
traits.
An
extensive variety of information was collected on more than
10,500 children, born in Southwest England between 1991-92,
including:
-
A wide range of measures of reading,
language and speech abilities, which have been collected
at ALSPAC annual visits from year 7 and 13 of the
participants.
-
Much relevant data on the environment
where the children grow up. (Of particular interest are
measures that have already been proposed as risk factors for
dyslexia and SLI, such as parental sensitivity and
responsiveness, or the home literacy environment and Omega-3
fatty acid consumption).
-
DNA from the children, for genetic
analysis.
The
project will therefore be able to access a wide range of data on
this sample, from diet details, to the number of books the
children could access during their infancy.
From
all these measures, a more restricted number will be selected
for further analysis during the project.
In
addition, some measures of attention and hyperactivity behaviour
will also be selected. (This is because attention deficit
hyperactivity disorder (ADHD) shows extensive co-morbidity
with both dyslexia and SLI.)
1.2 Analyses:
The
entire ALSPAC sample will be genotyped for markers within
candidate genes for dyslexia and SLI.
Sequenom iPLEX genotyping technology will be used,
which allows the analysis of up to 40 markers simultaneously.
The
project will investigate how individual risk factors
(genetic and environmental) for
dyslexia and SLI interact with one another, by conducting the
following analyses:
-
Gene x gene interaction analysis to
test whether different dyslexia and SLI susceptibility
variants interact with one another, in determining the two
disorders.
-
Gene x environment interaction analysis
to test whether environmental factors contribute in
modulating the effect of genes associated with dyslexia and
SLI.
-
An analysis to test whether the observed
co-morbidity between dyslexia and SLI is determined by
shared genetic or environmental factors , and whether it
is possible to identify a correlation between
genetic/environment background and specific sub-groups of
phenotypes.
Understanding the interplay of multiple factors will be crucial
to defining the causes of these common disorders, as well as the
mechanisms underlying important aspects of cognition and
behaviour, such as language and literacy skills.
This
project will therefore have important clinical implications in
the future for diagnosis and implementation of more effective
therapy intervention.
About
5% of school-age children have difficulties with reading
skills and development of language that are not due to low
intelligence or inadequate educational opportunity.
These
problems are called specific reading disability (or dyslexia)
and specific language impairment (SLI):
Dyslexia is a specific
difficulty in learning to read that cannot be explained by
obvious causes.
Specific Language Impairment (SLI)
is a marked impairment in the development of expressive and/or
receptive language.
For
both dyslexia and SLI, there is evidence for contribution from
both genetic and environmental factors, which probably
have to act together.
The
major goal of this MRC-funded project is to investigate how these individual
risk factors interact with one another.
Ultimately, this research aims to enable the earlier
diagnosis of both disorders. This
is fundamental to developing effective intervention therapies.
For
example dyslexia is currently diagnosed when children are
exposed to written language at school, often too late to start a
successful intervention programme.
The
detection of predisposing genetic factors, risk environmental
exposures, and their interplay, would contribute to identifying
those children, of pre-school age, who might benefit from
specialised assistance.
The
identification of environmental factors that increase the
likelihood of developing dyslexia or SLI might also have an
important impact on prevention.
The
project will also investigate whether there is a connection
between specific combinations of predisposing factors and
performance in well-defined measures of language and reading
skills.
This
aspect of the research will contribute to identifying a
sub-group of patients for which it would be possible to design
targeted intervention therapies.
3. Collaborators
-
Patrick Bolton (London)
-
Dorothy Bishop (Oxford)
4. Links
5. Funders
6. Contact
For further information about this project,
please contact Dr Silvia
Paracchini at
silviap@well.ox.ac.uk
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