title: Genome-wide screening for DNA variants associated with reading and language traits.
abstract: Reading and language abilities are heritable traits that are likely to share some genetic influences with each other. To identify pleiotropic genetic variants affecting these traits, we first performed a genome-wide association scan (GWAS) meta-analysis using three richly characterized datasets comprising individuals with histories of reading or language problems, and their siblings. GWAS was performed in a total of 1862 participants using the first principal component computed from several quantitative measures of reading- and language-related abilities, both before and after adjustment for performance IQ. We identified novel suggestive associations at the SNPs rs59197085 and rs5995177 (uncorrected P ≈ 10(-7) for each SNP), located respectively at the CCDC136/FLNC and RBFOX2 genes. Each of these SNPs then showed evidence for effects across multiple reading and language traits in univariate association testing against the individual traits. FLNC encodes a structural protein involved in cytoskeleton remodelling, while RBFOX2 is an important regulator of alternative splicing in neurons. The CCDC136/FLNC locus showed association with a comparable reading/language measure in an independent sample of 6434 participants from the general population, although involving distinct alleles of the associated SNP. Our datasets will form an important part of on-going international efforts to identify genes contributing to reading and language skills.
authors: Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
authors: A
authors: A
authors: Gialluisi
authors: D F
authors: DF
authors: Newbury
authors: E G
authors: EG
authors: Wilcutt
authors: R K
authors: RK
authors: Olson
authors: J C
authors: JC
authors: DeFries
authors: W M
authors: WM
authors: Brandler
authors: B F
authors: BF
authors: Pennington
authors: S D
authors: SD
authors: Smith
authors: T S
authors: TS
authors: Scerri
authors: N H
authors: NH
authors: Simpson
authors: M
authors: M
authors: Luciano
authors: D M
authors: DM
authors: Evans
authors: T C
authors: TC
authors: Bates
authors: J F
authors: JF
authors: Stein
authors: J B
authors: JB
authors: Talcott
authors: A P
authors: AP
authors: Monaco
authors: S
authors: S
authors: Paracchini
authors: C
authors: C
authors: Francks
authors: S E
authors: SE
authors: Fisher
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D004410:Dyslexia / Q000235:genetics*; D005260:Female; D058685:Genetic Pleiotropy; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007807:Language Tests; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics
chemical_list: C491796:CCDC136 protein, human; D009363:Neoplasm Proteins; C454924:RBFOX2 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D012097:Repressor Proteins
keywords: CLDRC; GWAS; SLIC; developmental dyslexia; language; meta-analysis; pleiotropic variants; reading; reading disability; specific language impairment