Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia

Show full item record



Permalink

http://hdl.handle.net/10138/300316

Citation

Gialluisi , A , Andlauer , T F M , Mirza-Schreiber , N , Moll , K , Becker , J , Hoffmann , P , Ludwig , K U , Czamara , D , St Pourcain , B , Brandler , W , Honbolygo , F , Toth , D , Csepe , V , Huguet , G , Morris , A P , Hulslander , J , Willcutt , E G , DeFries , J C , Olson , R K , Smith , S D , Pennington , B F , Vaessen , A , Maurer , U , Lyytinen , H , Peyrard-Janvid , M , Leppanen , P H T , Brandeis , D , Bonte , M , Stein , J F , Talcott , J B , Fauchereau , F , Wilcke , A , Francks , C , Bourgeron , T , Monaco , A P , Ramus , F , Landerl , K , Kere , J , Scerri , T S , Paracchini , S , Fisher , S E , Schumacher , J , Noethen , M M , Mueller-Myhsok , B & Schulte-Koerne , G 2019 , ' Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia ' , Translational Psychiatry , vol. 9 , 77 . https://doi.org/10.1038/s41398-019-0402-0

Title: Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia
Author: Gialluisi, Alessandro; Andlauer, Till F. M.; Mirza-Schreiber, Nazanin; Moll, Kristina; Becker, Jessica; Hoffmann, Per; Ludwig, Kerstin U.; Czamara, Darina; St Pourcain, Beate; Brandler, William; Honbolygo, Ferenc; Toth, Denes; Csepe, Valeria; Huguet, Guillaume; Morris, Andrew P.; Hulslander, Jacqueline; Willcutt, Erik G.; DeFries, John C.; Olson, Richard K.; Smith, Shelley D.; Pennington, Bruce F.; Vaessen, Anniek; Maurer, Urs; Lyytinen, Heikki; Peyrard-Janvid, Myriam; Leppanen, Paavo H. T.; Brandeis, Daniel; Bonte, Milene; Stein, John F.; Talcott, Joel B.; Fauchereau, Fabien; Wilcke, Arndt; Francks, Clyde; Bourgeron, Thomas; Monaco, Anthony P.; Ramus, Franck; Landerl, Karin; Kere, Juha; Scerri, Thomas S.; Paracchini, Silvia; Fisher, Simon E.; Schumacher, Johannes; Noethen, Markus M.; Mueller-Myhsok, Bertram; Schulte-Koerne, Gerd
Other contributor: University of Helsinki, STEMM - Stem Cells and Metabolism Research Program



Date: 2019-02-11
Language: eng
Number of pages: 15
Belongs to series: Translational Psychiatry
ISSN: 2158-3188
DOI: https://doi.org/10.1038/s41398-019-0402-0
URI: http://hdl.handle.net/10138/300316
Abstract: Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562-3468). We observed a genome-wide significant effect (p <1 x 10(-8)) on rapid automatized naming of letters (RANlet) for variants on 18q12.2, within MIR924HG (micro-RNA 924 host gene; rs17663182 p = 4.73 x 10(-9)), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter; rs16928927, p = 2.25 x 10(-8)). rs17663182 (18q12.2) also showed genome-wide significant multivariate associations with RAN measures (p = 1.15 x 10(-8)) and with all the cognitive traits tested (p = 3.07 x 10(-8)), suggesting (relational) pleiotropic effects of this variant. A polygenic risk score (PRS) analysis revealed significant genetic overlaps of some of the DD-related traits with educational attainment (EDUyears) and ADHD. Reading and spelling abilities were positively associated with EDUyears (p similar to [10(-5)-10(-7)]) and negatively associated with ADHD PRS (p similar to [10(-8)-10(-17)]). This corroborates a long-standing hypothesis on the partly shared genetic etiology of DD and ADHD, at the genome-wide level. Our findings suggest new candidate DD susceptibility genes and provide new insights into the genetics of dyslexia and its comorbities.
Subject: AUTOMATIZED NAMING RAN
SHORT-TERM-MEMORY
READING-DISABILITY
DEVELOPMENTAL DYSLEXIA
ENVIRONMENTAL-INFLUENCES
SUSCEPTIBILITY LOCUS
MOLECULAR-GENETICS
IMAGING-GENETICS
CANDIDATE GENES
LANGUAGE
3124 Neurology and psychiatry
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
s41398_019_0402_0.pdf 1.491Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record