Gene x gene and gene x environment interactions underlying speech, language and reading development

About 5% of school-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 (dyslexia) and specific language impairment (SLI). For both disorders there is evidence for contribution from both genetic and environmental factors that probably have to act together. Research advances have now identified several of these factors of both genetic and environmental nature. The aim of this proposal is to test how different risk factors interact with one another in order to cause dyslexia and SLI, as we wanted to find the correct order for the many pieces of a complicated jigsaw puzzle.
We will carry out our research in the ALSPAC sample, a large project that has collected an extensive variety of information on more than 10,000 children born in Southwest England between 1991-92. We will be able to combine all the variables of our study in the ALSPAC sample. We can use the DNA from the children for genetic analysis, and we can access their scores on measures of language and reading skills, together with the relevant information about the environment where they are growing up. We will be able to look at data ranging from diet details to the number of books the children could access during their infancy.
This research investigates whether there is a connection between specific combinations of predisposing factors and performance in well-defined measures of language and reading skills. The aim is to identify sub-groups of children for whom it will be possible to design more targeted and, therefore, more effective intervention therapies. This project will also contribute to develop strategies for early diagnosis of these disorders, which is fundamental to the implementation of intervention programs. For example, dyslexia is currently diagnosed when children are exposed to written language at school, often too late to start a successful theraphy. The detection of predisposing genetic factors, environmental exposures and their interplay will help to identify those children of pre-school age who might benefit from receiving specialised help. The identification of environmental factors that increase the likelihood of developing dyslexia or SLI might also have an important impact on prevention.
Ultimately, this project will contribute to our understanding of the mechanisms underlying behaviour and cognition.

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. Both SLI and dyslexia are complex traits most likely caused by multiple genetic and environmental factors. Research progress to date has identified several individual risk factors both of genetic and environmental nature.
The major aim of this project is to investigate how these factors interact with one another by specifically conducting 1) a gene x gene interaction analysis to test whether the interaction of different dyslexia and SLI susceptibility variants contribute to determine the two disorders; 2) a gene x environment interaction analysis to test whether environmental factors contribute in modulating the effect of genes associated with dyslexia and SLI; and 3) 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/environmental background and specific sub-groups of phenotypes.
We will conduct our analysis in the ALSPAC sample, a large epidemiological cohort 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. We will genotype the entire ALSPAC cohort (N = 10,000) for markers within candidate genes for dyslexia and SLI, using the Sequenom iPLEX technology which allows the analysis of up to 40 markers simultaneously. For the analysis we will select a wide range of measures of reading, language and articulation which have been collected from participants at ALSPAC annual visits from years 7 and 13. We will also use related cognitive phenotype measures of attention and hyperactivity behaviour since attention deficit hyperactivity disorder (ADHD) shows extensive co-morbidity with both dyslexia and SLI. The environmental factors will include measures that have already been proposed as risk factors for dyslexia and SLI such as home literacy environment and Omega-3 fatty acid consumption, or family structure and parental sensitivity.
The understanding of the interplay of multiple factors will be crucial to define the aetiology 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 have important clinical implications in the future for diagnosis and implementation of more effective therapies.