Genome Wide Association Scan identifies new variants associated with a cognitive predictor of dyslexia.
Till F. M. Andlauer,
Kerstin U Ludwig,
Beate St Pourcain,
Andrew P Morris,
Erik G Willcutt,
John C DeFries,
Richard K Olson,
Shelley D Smith,
Bruce F Pennington,
Paavo H T Leppänen,
John F Stein,
Joel B Talcott,
Anthony P Monaco,
Thomas S Scerri,
Simon E. Fisher,
Markus M. Nöthen,
Posted 02 May 2018
bioRxiv DOI: 10.1101/309336 (published DOI: 10.1038/s41398-019-0402-0)
Posted 02 May 2018
Developmental dyslexia (DD) is one of the most prevalent learning disorders among children and is characterized by deficits in different cognitive skills, including reading, spelling, short term memory and others. To help unravel the genetic basis of these skills, we conducted a Genome Wide Association Study (GWAS), including nine cohorts of reading-impaired and typically developing children of European ancestry, recruited across different countries (N=2,562-3,468). We observed a genome-wide significant effect (p<1x10-8) on rapid automatized naming of letters (RANlet) for variants on 18q12.2 within MIR924HG (micro-RNA 924 host gene; p = 4.73x10-9), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter; p = 2.25x10-8). RAN represents one of the best universal predictors of reading fluency across orthographies and linkage to RAN has been previously reported within CELF4 (18q12.2), a gene highly expressed in the fetal brain which is co-expressed with NKAIN3 and predicted to be a target of MIR924. These findings suggest new candidate DD susceptibility genes and provide insights into the genetics and neurobiology of dyslexia.
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