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.
Original language | English (US) |
---|---|
Pages (from-to) | 686-701 |
Number of pages | 16 |
Journal | Genes, Brain and Behavior |
Volume | 13 |
Issue number | 7 |
DOIs | |
State | Published - 2014 |
Keywords
- CLDRC
- Developmental dyslexia
- GWAS
- Language
- Meta-analysis
- Pleiotropic variants
- Reading
- Reading disability
- SLIC
- Specific language impairment
ASJC Scopus subject areas
- Genetics
- Neurology
- Behavioral Neuroscience