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Handedness has been studied for association with language-related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non-right-handedness (NRH) frequency was assessed in N = 2503 cases with reading and/or language impairment and N = 4316 sex-matched controls identified from 10 distinct cohorts (age range 6-19 years old; European ethnicity) using a priori set criteria. A meta-analysis (N cases  = 1994) showed elevated NRH % in individuals with language/reading impairment compared with controls (OR = 1.21, CI = 1.06-1.39, p = .01). The association between reading/language impairments and NRH could result from shared pathways underlying brain lateralization, handedness, and cognitive functions., (© 2023 The Authors. Child Development published by Wiley Periodicals LLC on behalf of Society for Research in Child Development.)

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10 -8 ) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.

Dyslexia is a common condition affecting up to 10% school-aged children. There is strong evidence that genetics plays an important role in dyslexia and is expected to be complex in nature. Few specific susceptibility factors have been identified so far, but their functional characterization has provided novel insights into the biology of dyslexia. In particular, they point to an unexpected role of candidate genes for dyslexia in the biology of cilia, cellular organelles required in many processes including the establishment of left-right asymmetries early in development. This observation has brought back into the spotlight the old idea of a link between dyslexia and handedness. Yet much of the genetics contributing to dyslexia remains unexplained. The lack of biological markers, clear diagnostic criteria, and homogeneous assessment strategies are just some of the factors preventing the collection of the cohorts powered enough for large-scale genetic studies. While the technology and methods to generate and handle large-scale data have reached unprecedented potential, the main challenge remains in establishing universal guidelines to collect suitable phenotype information across independent studies. These difficulties reflect the complex nature of dyslexia which is highly heterogeneous and often co-occurs with other neurodevelopmental disorders., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Several susceptibility genes have been proposed for dyslexia (reading disability; RD) and specific language impairment (SLI). RD and SLI show comorbidity, but it is unclear whether a common genetic component is shared., Methods: We have investigated whether candidate genes for RD and SLI affect specific cognitive traits or have broad effect on cognition. We have analyzed common risk variants within RD (MRPL19/C2ORF3, KIAA0319, and DCDC2) and language impairment (CMIP and ATP2C2) candidate loci in the Avon Longitudinal Study of Parents and Children cohort (n = 3725), representing children born in southwest England in the early 1990s., Results: We detected associations between reading skills and KIAA0319, DCDC2, and CMIP. We show that DCDC2 is specifically associated with RD, whereas variants in CMIP and KIAA0319 are associated with reading skills across the ability range. The strongest associations were restricted to single-word reading and spelling measures, suggesting that these genes do not extend their effect to other reading and language-related skills. Inclusion of individuals with comorbidity tends to strengthen these associations. Our data do not support MRPL19/C2ORF3 as a locus involved in reading abilities nor CMIP/ATP2C2 as genes regulating language skills., Conclusions: We provide further support for the role of KIAA0319 and DCDC2 in contributing to reading abilities and novel evidence that the language-disorder candidate gene CMIP is also implicated in reading processes. Additionally, we present novel data to evaluate the prevalence and comorbidity of RD and SLI, and we recommend not excluding individuals with comorbid RD and SLI when designing genetic association studies for RD., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

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. [ABSTRACT FROM AUTHOR]