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Published Online: 17 June 2011

Genes May Forge Relationship Between ADHD, Dyslexia

Abstract

The link between two particular genes and dyslexia is especially strong when a person has ADHD and dyslexia. The reason for this association is unclear, though dyslexia and ADHD are often comorbid.
Thanks to a large population study, evidence from clinical samples has become more compelling that two particular genes contribute to dyslexia.
One gene is called DCDC2, the other KIAA0319. Both are located on chromosome 6, near each other, and both have been shown to play a role in neuronal migration during cerebral development. (Defects in neuronal migration contribute to mental retardation and epilepsy.)
The lead investigator was Silvia Paracchini, Ph.D., of the Wellcome Trust Centre for Human Genetics at the University of Oxford in England. The findings were published online April 4 in Biological Psychiatry.
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The study cohort consisted of 3,725 children born in southwest England in the early 1990s: 171 had dyslexia; 186 had specific language impairment (SLI), a developmental language disorder that can affect both expressive and receptive language and symptoms of which include the use of short sentences and difficulty in producing and understanding syntactically complex sentences; 46 had both dyslexia and SLI; 26 had attention-deficit/hyperactivity disorder (ADHD); and 13 had dyslexia plus ADHD, SLI plus ADHD, or dyslexia, SLI, and ADHD.
All subjects were genotyped. The scientists found that variants of two genes on chromosome 6 that had been previously linked with dyslexia in clinical samples—DCDC2 and KIAA0319—were present significantly more often in their subjects with dyslexia than in their subjects without the condition.
Also, the link between dyslexia and the DCDC2 gene was even stronger when subjects had dyslexia combined with SLI and/or ADHD than when they had dyslexia alone. The situation was similar, but not as strong, for the KIAA0319 gene.
The reason for the association is not known, but there are several possible explanations, Paracchini told Psychiatric News. For example, the link might have been stronger in individuals with dyslexia plus SLI and/or ADHD than in individuals with dyslexia alone because the former had a particularly severe form of dyslexia. "This hypothesis fits with previous studies in clinical samples where gene associations were stronger in the most severe subgroups of individuals with dyslexia," Paracchini said.
Nonetheless, the findings appear to have clinical implications, Paracchini believes. For example, it looks as if the same genetic and cognitive deficits underlie dyslexia regardless of whether dyslexia is accompanied by SLI or ADHD. "Such knowledge will hopefully lead to better diagnosis of, and treatment for, dyslexia," she said.
The findings also raise this question: might ADHD also be coded, at least in part, by genes located close to the two dyslexia genes on chromosome 6? Probably not, Parrachini stated. Many genes have been implicated in ADHD, but none of them is located in the same region of chromosome 6 as the two dyslexia genes, she said.
"As an academic child psychiatrist, I found this to be provocative research," said Sonja Randle, M.D., an assistant professor of psychiatry and behavioral sciences at the University of Texas Health Science Center at Houston. "I was intrigued by the associations they made regarding comorbidity. They were able to show for the first time that inclusion of individuals with comorbid dyslexia, SLI, or ADHD does not weaken the associations, but rather can strengthen [them] … . This information could have a huge impact on how these types of studies are done in the future. They suggest that individuals with dyslexia comorbid for SLI or ADHD should not be excluded when designing genetic studies of dyslexia because their inclusion could improve sample power."
The study, Randle pointed out, "also supports the importance of looking at the biopsychosocial factors that impact psychiatric and developmental disorders. Parents are often reluctant to talk about how their children did in school, but getting a good family and developmental history can help identify potential genetic linkages that are also supported in the literature."
The study was funded by the United Kingdom Medical Research Council and the Wellcome Trust.
An abstract of "DCDC2, KIAA0319, and CMIP Are Associated With Reading-Related Traits" is posted at <www.biologicalpsychiatryjournal.com/article/S0006-3223(11)00135-1/abstract>.

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Published online: 17 June 2011
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