Elsevier

The Lancet Neurology

Volume 1, Issue 8, December 2002, Pages 483-490
The Lancet Neurology

Review
The genetic basis of dyslexia

https://doi.org/10.1016/S1474-4422(02)00221-1Get rights and content

Summary

Dyslexia, a disorder of reading and spelling, is a heterogeneous neurological syndrome with a complex genetic and environmental aetiology. People with dyslexia differ in their individual profiles across a range of cognitive, physiological, and behavioural measures related to reading disability. Some or all of the subtypes of dyslexia might have partly or wholly distinct genetic causes. An understanding of the role of genetics in dyslexia could help to diagnose and treat susceptible children more effectively and rapidly than is currently possible and in ways that account for their individual disabilities. This knowledge will also give new insights into the neurobiology of reading and language cognition. Genetic linkage analysis has identified regions of the genome that might harbour inherited variants that cause reading disability. In particular, loci on chromosomes 6 and 18 have shown strong and replicable effects on reading abilities. These genomic regions contain tens or hundreds of candidate genes, and studies aimed at the identification of the specific causal genetic variants are underway.

Section snippets

Biology of reading

Reading is a complex multicomponent process both physiologically2 and cognitively.8, 12 In brief outline, reading must begin with sensing of visual stimuli and processing of information through the pathway of retina, lateral geniculate nuclei, and primary visual cortex.13 At some stage, visual information is probably made available to neuronal systems that apply learned, language-specific rules to convert symbolic images into component representations of language.14 In this form, the

Cognitive aspects of reading

Researchers typically attempt to dissect the cognition of reading into conceptually distinct component skills. The close relation between reading and language lies at the heart of many efforts to identify cognitive deficits involved in dyslexia. In particular, the form in which deconstructed language is processed has provided the main focus for cognitive models of reading disability.27 In this regard, dyslexia research overlaps with research into specific language impairment (SLI), a closely

Development

In cognitive terms, single-word reading is sometimes described as a multicomponent process, intermediate in a nested hierarchy of processes that range from basic phoneme processing to the overall comprehension of extended text. As such, single-word-reading ability has been described as a broad and definitive indicator of reading skill,34 with population variance in some of the other component skills thought to account for the overall variance within single-word-reading measures.8

However,

Genetic epidemiology

A genetic involvement in dyslexia has long been evident from studies showing familial clustering of the disorder1, 3, 38 and more recently through twin studies.6, 7, 8, 9, 12 In twin studies, monozygotic twins will be, on average, more similar for measures that are heritable than dizygotic twins, since monozygotic pairs share all of their segregating alleles identical-by-descent from their parents, as opposed to dizygotic twins who share, on average, half.46 Environmental effects are assumed to

Genetic dissection

Do different cognitive processes involved in reading develop independently of one another to some degree? If so, the existence of different genetic subtypes of dyslexia might be identified through epidemiological and gene mapping studies. In a pioneering study, Olson and colleagues8 used a modification of Defries-Fulker regression (figure 1) on their Colorado twin data, in which probands were selected on one cognitive variable and co-twin regression was assessed on a different but correlated

Gene mapping

Recent advances in high-throughput molecular genetic techniques and statistical methods have made possible several large-scale studies aimed at identification and mapping of the genetic variants that underlie individual differences in reading ability.10, 11 The identification of these genetic variants will allow more sophisticated analyses of the links between different reading-related cognitive, physiological, and behavioural measures than has been possible, which could lead to the

Studies so far

For the reasons described above, dyslexia researchers have tended to use linkage analysis in the first instance to identify broad genomic regions that contain tens or hundreds of potential candidate genes,11 and association analysis is used within these defined regions. Various linkage studies have been done, and many regions of the genome that might harbour genetic variants that predispose to dyslexia have been identified.10, 11, 34, 35, 36, 37, 44, 45, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69,

Conclusion

One aim of molecular genetic research into dyslexia is to provide a better understanding of the specific problems that affect individual children with dyslexia, since there are subtypes of dyslexia that may be influenced by partly distinct genetic factors. Linkage mapping studies, the first of which have now been completed, are the first steps towards a molecular genetic dissection of dyslexia.78 Genetic association studies are now under way,58, 79, 80 targeted within the genomic regions

Search strategy and selection criteria

Data for this review were identified by searches of PubMed and references from relevant articles; articles were also identified through searches of the files of the authors. The search terms “dyslexia” and “reading disability” were used. Only papers written in English were reviewed.

GLOSSARY

Phonological awareness
Ability to reflect explicitly on, and manipulate, the units of spoken language.
Phonological decoding
Parsing written text into phonetic units, usually measured by reading of nonsense words (eg, tegwop).
Orthographic coding
Reading words by recognising their holistic form, usually measured by reading irregular words that violate standard letter-sound conventions (eg, yacht).
Word recognition or single-word reading
Reading of single real words of various types and difficulties as

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