Genome-wide screening for DNA variants associated with reading and language traits

The SLI Consortium

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)686-701
Number of pages16
JournalGenes, Brain and Behavior
Volume13
Issue number7
DOIs
StatePublished - Jan 1 2014

Fingerprint

Reading
Language
Genome
Single Nucleotide Polymorphism
DNA
Aptitude
Genome-Wide Association Study
Alternative Splicing
Cytoskeleton
Genes
Meta-Analysis
Alleles
Neurons
Population
Proteins
Datasets

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

Cite this

Genome-wide screening for DNA variants associated with reading and language traits. / The SLI Consortium.

In: Genes, Brain and Behavior, Vol. 13, No. 7, 01.01.2014, p. 686-701.

Research output: Contribution to journalArticle

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N2 - 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.

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