Project summary

22,750,000 dyslexic individuals, including 2,500,000 dyslexic school children in the EC have a specific disorder in learning to read and spell (dyslexia). Since dyslexia occurs in all languages and presents a lifelong burden characterized by academic failure, poor school attendance, problems with social adjustments and unemployment.

So far the etiology of dyslexia is poorly understood. Therefore, it is mandatory to tackle the problem from several directions.

In a multicentre, multidisciplinary project we will investigate the biological basis of dyslexia by collecting powerful samples of subjects consistently characterised across EC populations on three different levels: genetics, environment, and neuroscience. Our aim is to understand the etiology of the disorder by integrating the results of the three levels.

On the genetic level, we will use a systematic two stage approach to map and clone dyslexia susceptibility genes in samples of 800 families and 1950 dyslexic cases and 1950 controls. The identified risk-conferring genes will also be used to understand gene-gene and gene-environment interactions, as well as gene-specific contributions to a variety of neurobiological correlates of dyslexia.

Environmental risk factors will be investigated in two samples, a longitudinal sample of 4000 twin pairs and a longitudinal sample of 100 at-risk and 100 non at-risk children.

On the neuroscience level (structural and functional brain studies including cutting edge technology such as effective connectivity) we will investigate the prerequisites of reading and spelling development and the central stages of becoming a fluent reader.

The resulting research group will be a high quality, adaptive and cooperative European consortium composed of psychologists, molecular biologists/geneticists, clinicians and genetic statisticians. With these combined efforts we are confident to improve the basis for the development of successful diagnostics and therapies.

Total cost (€)3.040.000,00

Commission funding (€)3.040.000,00

Project main goal

The key to reinforcing competitiveness is to identify candidate genes and the neurobiological basis of dyslexia that can be rapidly used to develop and evaluate novel treatment approaches as well as early diagnostics by the industries, thereby reducing the “lead time” between fun-damental knowledge and practical exploitation, and making efficient use of the resources in-vested in this vitally important research area at the European level.

Key issues

Dyslexia is one of the very common learning disorders around the world with a prevalence about at least 5% - 10% of the school age children. At least 22,750,000 EU citizens are affected and perhaps another million in those countries seeking to join. The societal impact of dyslexia is as follows: higher incidence of dyslexia within the prison and probation populations, higher incidence of school drop out, higher incidence of long term unemployment. Other consequences for dyslexia include are that dyslexia increases the risk for psychiatric disorders like emotional and affective disorder, and conduct disorders.

For dyslexia there is a long tradition of high standards both at the national and international level in Europe. Through previous and ongoing collaborations between members of the NEURODYS consortium, the clinical and genetic characterization of a large number of patients/families was made possible across Europe. Several participating groups have individually contributed to the European Science Foundation (ESF).

The clinical teams have ascertained a large number of families and individuals with dyslexia. This sample includes multiplex, nuclear and affected sib pair families previously used in genome wide scans as well as new families not yet genome scanned. The NEURODYS project will contribute to the European standards in the field of dyslexia by centralising the genetic and functional brain studies on Dyslexia. There is yet no integrated plan to bring together different research centres to achieve the critical mass necessary to clarify the disease mechanisms. Our project will ensure the integration and strengthening of the EU 6th Framework Programme Research Area on “Genomics and biotechnology for health” as it applies to dys-lexia as a whole. It will use the clinical, neurobiological and genetic information obtained through previously funded work in Europe to understand the biological function and dysfunction of the central nervous system, opening the way for effective treatments.

Technical approach

In this multicentre, multidisciplinary project we will investigate the biological basis of dyslexia by collecting powerful samples of subjects consistently characterised across EC populations on three different levels: genetics, environment, and neuroscience.

Environmental risk factors will be investigated in two samples, a longitudinal sample of 4000 twin pairs and a longitudinal sample of 100 at-risk and 100 non at-risk children.

On the neuroscience level (structural and functional brain studies including cutting edge tech-nology such as effective connectivity) we will investigate the prerequisites of reading and spelling development and the central stages of becoming a fluent reader.

This project uses state of the art technical approaches (genotyping, statistical genetic analyses, brain imaging) to gain knowledge about candidate genes and the neurobiological pathway for dyslexia. The coordinate approach to this task across five moleculargenetic laboratories (Bonn, Cardiff, Oxford, Paris, Stockholm), three neuroimaging laboratories (Maastricht, Salzburg, Zürich) and four electrophysiological laboratories (Budapest, Jyväskylä, Marburg, Toulouse) will maximize laboratory efficiency. The use of a three step candidate gene ap-proach of 800 trios (dyslexic child and both parents) and 1950 dyslexic individuals and 1950 controls, information of public haplotype map and high-throughput genotyping methodologies optimises the potential for European samples and laboratories to achieve significant technical advances.

This proposal will outperform the former brain imaging studies on dyslexia by applying a ground breaking new methodological approach; the mapping of effective connectivity in the brain using Granger causality and fMRI (Goebel et al, 2003, Roebroeck et al, in press). This will not only allow us to localize the neural correlates of the targeted perceptual and cognitive reading processes, but will also allow to model interactions between identified active brain regions in dyslexic and normal reading children. This method (Goebel et al., 2003, Roebroeck et al., in press) does not require preselection of regions as is necessary with previous effective connectivity methods (i.e. Structural Equation Models, Dynamic Causal Models) and is the first method which is able to map effective connectivity over the brain using vector autoregressive (VAR) modelling of fMRI time series in the context of Granger causality.

Expected achievement/impact

The knowledge gained in this project will lead to the discovery of the underlying causes of dyslexia and of the development early diagnostic instruments as well as specific treatments. The exploitation of new treatments approaches will improve health, and quality of life in Europe. Additionally, this offers new possibilities for wealth creation as new knowledge is exploited by industries developing rehabilitation, therapy, and diagnostic tools and as the financial burden on our health care systems is diminished.

We will provide information that will enable society to understand this disease, increasing public and governmental awareness of the scale of the problem, the underlying cause, the ongoing research and the hope for new therapy. Our collective research efforts will raise awareness at national and European levels, as part of our mission to help prevent Europe from experiencing a high number of dyslexic children to that already seen in the US.