Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people.

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.

Oral language enrichment in preschool improves children's language skills: a cluster randomised controlled trial.

BACKGROUND: Oral language skills provide the foundation for formal education, yet many children enter school with language weaknesses. This study evaluated the efficacy of a new language enrichment programme, the Nuffield Early Language Intervention-Preschool (NELI Preschool), delivered to children in the year before they enter formal education. METHODS: We conducted a preregistered cluster randomised controlled trial in 65 nursery schools in England (https://doi.org/10.1186/ISRCTN29838552). NELI Preschool consists of a 20-week whole-class language enrichment programme delivered by a teacher each day for 20 min. In addition, children with the weakest language skills in each class are allocated to receive additional targeted support delivered by classroom assistants (whole-class + targeted). The language skills of all children (n = 1,586) in participating classrooms were assessed using the LanguageScreen automated app (https://oxedandassessment.com/languagescreen/). Settings were then randomly allocated to an intervention or control group. The children with the weakest language in each class (whole-class + targeted children n = 438), along with four randomly selected children in each class allocated to the whole-class only programme (n = 288) were individually tested on a range of language measures. RESULTS: Children receiving NELI Preschool made larger gains than children in the control group on an oral language latent variable (whole-class children d = .26; whole-class + targeted children d = .16). CONCLUSIONS: This study provides good evidence that whole-class intervention delivered in preschool can produce educationally significant improvements in children's language skills. The intervention is scaleable and relatively low cost. These findings have important implications for educational and social policy.

A rare missense variant in the ATP2C2 gene is associated with language impairment and related measures.

At least 5% of children present unexpected difficulties in expressing and understanding spoken language. This condition is highly heritable and often co-occurs with other neurodevelopmental disorders such as dyslexia and ADHD. Through an exome sequencing analysis, we identified a rare missense variant (chr16:84405221, GRCh38.p12) in the ATP2C2 gene. ATP2C2 was implicated in language disorders by linkage and association studies, and exactly the same variant was reported previously in a different exome sequencing study for language impairment (LI). We followed up this finding by genotyping the mutation in cohorts selected for LI and comorbid disorders. We found that the variant had a higher frequency in LI cases (1.8%, N = 360) compared with cohorts selected for dyslexia (0.8%, N = 520) and ADHD (0.7%, N = 150), which presented frequencies comparable to reference databases (0.9%, N = 24 046 gnomAD controls). Additionally, we observed that carriers of the rare variant identified from a general population cohort (N = 42, ALSPAC cohort) presented, as a group, lower scores on a range of reading and language-related measures compared to controls (N = 1825; minimum P = 0.002 for non-word reading). ATP2C2 encodes for an ATPase (SPCA2) that transports calcium and manganese ions into the Golgi lumen. Our functional characterization suggested that the rare variant influences the ATPase activity of SPCA2. Thus, our results further support the role of ATP2C2 locus in language-related phenotypes and pinpoint the possible effects of a specific rare variant at molecular level.

Language and reading impairments are associated with increased prevalence of non-right-handedness.

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 (Ncases  = 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.

Editorial Perspective: Speaking up for developmental language disorder - the top 10 priorities for research.

Developmental language disorder (DLD) is one of the most common neurodevelopmental conditions, yet is chronically underserved, with far fewer children receiving clinical services than expected from prevalence estimates, and very little research attention relative to other neurodevelopmental conditions of similar prevalence and severity. This editorial describes a research priority-setting exercise undertaken by the Royal College of Speech and Language Therapists, which aims to redress this imbalance. From consultations with researchers, practitioners and individuals with lived experience, 10 research priorities emerge. Our goal is to share these priorities with the wider research community, to raise awareness and encourage research collaboration to improve outcomes for young people with DLD.

The nature and causes of children's grammatical difficulties: Evidence from an intervention to improve past tense marking in children with Down syndrome.

Children with language learning difficulties frequently display problems learning grammar. One such group is children with Down syndrome. This study evaluates the effectiveness of an intervention to teach the use of the regular simple past tense to children with Down syndrome. Trained teaching assistants delivered the intervention for 20 min per day for 10 weeks. We conducted a Randomised Controlled Trial, with a waiting list control design in which the Intervention group (N = 26) received the intervention immediately, while the delayed intervention group (N = 26) received the intervention later. Immediately following the intervention, the intervention group showed significantly larger gains in the use of regular simple past tense forms (d = 1.63 on a composite measure of simple past tense formation) as well as generalisation to verbs not explicitly taught. In addition, following the intervention children made overregularisation errors by incorrectly using regular simple past tense marking for irregular verbs; such errors support the claim that children had acquired generative knowledge underlying past tense marking. The delayed intervention control group showed identical benefits from the intervention when they received it, and the gains shown by the intervention group were maintained at follow up testing. This study shows that children with Down syndrome, who display severe language difficulties, can be taught to use simple past tense marking. The theoretical and applied implications of these findings for understanding the nature, causes and treatments of children's language difficulties are discussed.

Annual Research Review: Reading disorders revisited - the critical importance of oral language.

This paper discusses research on reading disorders during the period since their classification within the overarching category of neurodevelopmental disorders (Journal of Child Psychology and Psychiatry, 53, 2012, 593). Following a review of the predictors of learning to read across languages, and the role of language skills as critical foundations for literacy, profiles of reading disorders are discussed and putative causal risk factors at the cognitive, biological, and environmental levels of explanation considered. Reading disorders are highly heritable and highly comorbid with disorders of language, attention, and other learning disorders, notably mathematics disorders. The home literacy environment, reflecting gene-environment correlation, is one of several factors that promote reading development and highlight an important target for intervention. The multiple deficit view of dyslexia (Cognition, 101, 2006, 385) suggests that risks accumulate to a diagnostic threshold although categorical diagnoses tend to be unstable. Implications for assessment and intervention are discussed.

Early language screening and intervention can be delivered successfully at scale: evidence from a cluster randomized controlled trial.

BACKGROUND: It is well established that oral language skills provide a critical foundation for formal education. This study evaluated the effectiveness of the Nuffield Early Language Intervention (NELI) programme in ameliorating language difficulties in the first year of school when delivered at scale. METHODS: We conducted a cluster randomized controlled trial (RCT) in 193 primary schools (containing 238 Reception classrooms). Schools were randomly allocated to either a 20-week oral language intervention or a business-as-usual control group. All classes (N = 5,879 children) in participating schools were screened by school staff using an automated App to assess children's oral language skills. Screening identified 1,173 children as eligible for language intervention: schools containing 571 of these children were allocated to the control group and 569 to the intervention group. RESULTS: Children receiving the NELI programme made significantly larger gains than the business-as-usual control group on a latent variable reflecting standardized measures of language ability (d = .26) and on the school-administered automated assessment of receptive and expressive language skills (d = .32). The effects of intervention did not vary as a function of home language background or gender. CONCLUSIONS: This study provides strong evidence for the effectiveness of a school-based language intervention programme (NELI) delivered at scale. These findings demonstrate that language difficulties can be identified by school-based testing and ameliorated by a TA delivered intervention; this has important implications for educational and social policy.

Speechreading in hearing children can be improved by training.

Visual information conveyed by a speaking face aids speech perception. In addition, children's ability to comprehend visual-only speech (speechreading ability) is related to phonological awareness and reading skills in both deaf and hearing children. We tested whether training speechreading would improve speechreading, phoneme blending, and reading ability in hearing children. Ninety-two hearing 4- to 5-year-old children were randomised into two groups: business-as-usual controls, and an intervention group, who completed three weeks of computerised speechreading training. The intervention group showed greater improvements in speechreading than the control group at post-test both immediately after training and 3 months later. This was the case for both trained and untrained words. There were no group effects on the phonological awareness or single-word reading tasks, although those with the lowest phoneme blending scores did show greater improvements in blending as a result of training. The improvement in speechreading in hearing children following brief training is encouraging. The results are also important in suggesting a hypothesis for future investigation: that a focus on visual speech information may contribute to phonological skills, not only in deaf children but also in hearing children who are at risk of reading difficulties. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=bBdpliGkbkY.

Non-pharmacological interventions for stuttering in children six years and younger.

BACKGROUND: Stuttering, or stammering as it is referred to in some countries, affects a child's ability to speak fluently. It is a common communication disorder, affecting 11% of children by four years of age. Stuttering can be characterized by sound, part word or whole word repetitions, sound prolongations, or blocking of sounds or airflow. Moments of stuttering can also be accompanied by non-verbal behaviours, including visible tension in the speaker's face, eye blinks or head nods. Stuttering can also negatively affect behavioural, social and emotional functioning. OBJECTIVES: Primary objective To assess the immediate and long-term effects of non-pharmacological interventions for stuttering on speech outcomes, communication attitudes, quality of life and potential adverse effects in children aged six years and younger. Secondary objective To describe the relationship between intervention effects and participant characteristics (i.e. child age, IQ, severity, sex and time since stuttering onset) at pretest. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsycINFO, nine other databases and two trial registers on 16 September 2020, and Open Grey on 20 October 2020. There were no limits in regards to language, year of publication or type of publication. We also searched the reference lists of included studies and requested data on unpublished trials from authors of published studies. We handsearched conference proceedings and programmes from relevant conferences. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs that assessed non-pharmacological interventions for stuttering in young children aged six years and younger. Eligible comparators were no intervention, wait list or management as usual. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified four eligible RCTs, all of which compared the Lidcombe Program to a wait-list control group. In total, 151 children aged between two and six years participated in the four included studies. In the Lidcombe Program, the parent and their child visit a speech and language therapist (SLT) in a clinic. One study conducted clinic visits by telephone. In each clinic visit, parents were taught how to conduct treatment at home. Two studies took place in Australia, one in New Zealand and one in Germany. Two studies were conducted for nine months, one for 16 weeks and one for 12 weeks. The frequency of clinic visits and practice sessions at home varied within the programme. One study was partially funded by the Rotary Club, Wiesbaden, Germany; and one was funded by the National Health and Medical Research Council of Australia. One study did not report funding sources and another reported that they did not receive any funding for the trial.  All four studies reported the outcome of stuttering frequency. One study also reported on speech efficiency, defined as articulation rate. No studies reported the other predetermined outcomes of this review, namely stuttering severity; communication attitudes; emotional, cognitive or psychosocial domains; or adverse effects.  The Lidcombe Program resulted in a lower stuttering frequency percentage syllables stuttered (% SS) than a wait-list control group at post-test, 12 weeks, 16 weeks and nine months postrandomization (mean difference (MD) -2.16, 95% confidence interval (CI) -3.48 to -0.84, 4 studies, 151 participants; P = 0.001; very low-certainty evidence).  However, as the Lidcombe Program is designed to take one to two years to complete, none of the participants in these studies had finished the complete intervention programme at any of the data collection points. We assessed stuttering frequency to have a high risk of overall bias due to high risk of bias in at least one domain within three of four included studies, and to have some concern of overall bias in the fourth, due to some concern in at least one domain. We found moderate-certainty evidence from one study showing that the Lidcombe Program may increase speech efficiency in young children. Only one study reported outcomes at long-term follow-up. The long-term effect of intervention could not be summarized, as the results for most of the children in the control group were missing. However, a within-group comparison was performed between the mean % SS at randomization and the mean % SS at the time of extended follow-up, and showed a significant reduction in frequency of stuttering.  AUTHORS' CONCLUSIONS: This systematic review indicates that the Lidcombe Program may result in lower stuttering frequency and higher speech efficiency than a wait-list control group in children aged up to six years at post-test. However, these results should be interpreted with caution due to the very low and moderate certainty of the evidence and the high risk of bias identified in the included studies. Thus, there is a need for further studies from independent researchers, to evaluate the immediate and long-term effects of other non-pharmacological interventions for stuttering compared to no intervention or a wait-list control group.

Separable effects of the approximate number system, symbolic number knowledge, and number ordering ability on early arithmetic development.

There is evidence that early variations in the development of an approximate number system (ANS) and symbolic number understanding are both influences on the later development of formal arithmetic skills. We report a large-scale (N = 552) longitudinal study of the predictors of arithmetic spanning a critical developmental period (the first 3 years of formal education). Variations in early knowledge of symbolic representations of number and the ordinal associations between them are direct predictors of later arithmetic skills. The development of number ordering ability is in turn predicted by earlier variations in arithmetic, the ANS (numerosity judgments), and rapid automatized naming (RAN). These findings have important implications for theories of numerical and arithmetical development and potentially for the teaching of these skills.

Language difficulties are a shared risk factor for both reading disorder and mathematics disorder.

Disorders of reading and mathematics co-occur at greater than chance rates, but they are often studied separately. This article reports the reading and arithmetic outcomes at 9 years of age from a longitudinal study of 224 children at high risk for dyslexia. Using a cutoff at the 10th centile, groups of children with reading disorder (RD), mathematics disorder (MD), and comorbid reading disorder and math disorder (RD&MD) were identified. The risk of these disorders was elevated in children selected in preschool with language difficulties or at family risk for dyslexia. There was a high degree of comorbidity between RD and MD, and many cases-particularly in the comorbid group-also reached the diagnostic threshold for developmental language disorder (DLD). On measures of language, phoneme awareness, rapid automatized naming (RAN) digits, and rated inattention, there was a stepwise pattern: RD > MD > RD&MD. Poor language was associated with each disorder and appears to be a cognitive risk factor for RD, MD, and RD&MD. These findings suggest that there are shared genetic risk factors operating for both RD and MD.

Dyslexia and Developmental Language Disorder: comorbid disorders with distinct effects on reading comprehension.

BACKGROUND: Reading comprehension draws on both decoding and linguistic comprehension, and poor reading comprehension can be the consequence of a deficit in either of these skills. METHODS: Using outcome data from the longitudinal Wellcome Language and Reading Project, we identified three groups of children at age 8 years: children with dyslexia (N = 21) who had deficits in decoding but not oral language, children with Developmental Language Disorder (DLD; N = 38) whose decoding skills were in the normal range, and children who met criteria for both dyslexia and DLD (N = 29). RESULTS: All three groups had reading comprehension difficulties at the ages of 8 and 9 years relative to TD controls though those of the children with dyslexia were mild (relative to TD controls, d = 0.51 at age 8, d = 0.60 at age 8); while the most severe problems were found in the comorbid dyslexia + DLD group (d = 1.79 at age 8, d = 2.06 at age 9) those with DLD also had significant difficulties (d = 1.56 at age 8, d = 1.56 at age 9). CONCLUSIONS: These findings confirm that children with dyslexia or DLD are at-risk for reading comprehension difficulties but for different reasons, because of weak decoding in the case of dyslexia or weak oral language skills in the case of DLD. Different forms of intervention are required for these groups of children, targeted to their particular area(s) of weakness.

The critical role of Arabic numeral knowledge as a longitudinal predictor of arithmetic development.

Understanding the cognitive underpinnings of children's arithmetic development has great theoretical and educational importance. Recent research suggests symbolic and nonsymbolic representations of number influence arithmetic development before and after school entry. We assessed nonverbal ability and general language skills as well as nonsymbolic (numerosity) and symbolic (numeral) comparison skills, counting, and Arabic numeral knowledge (numeral reading, writing, and identification) in preschool children (4 years of age). At 6 years of age, we reassessed nonsymbolic (numerosity) and symbolic (numeral) comparison and arithmetic. A latent variable path model showed that Arabic numeral knowledge (defined by numeral reading, writing, and identification at 4 years of age) was the sole unique predictor of arithmetic at 6 years. We conclude that knowledge of the association between spoken and Arabic numerals is one critical foundation for the development of formal arithmetic.

Learning to read in Chinese: Evidence for reciprocal relationships between word reading and oral language skills.

This study investigates the longitudinal predictors of the development of Chinese word reading skills and potential bidirectional relationships between Chinese word reading and oral language skills. We examine, in a 2-year longitudinal study, a wide range of theoretically important predictors (phonological awareness, tone awareness, morphological awareness, visual skills, rapid automatized naming, Pinyin knowledge, and vocabulary knowledge) of reading in 143 primary-school children living in mainland China. Initial levels of reading were predicted by vocabulary knowledge, phonological awareness, and visual discrimination skills. Only initial reading levels predicted growth in reading. Initial reading also predicted growth in vocabulary knowledge and morphological construction. This pattern demonstrates that the early stages of learning to read in Chinese places demands on semantic (vocabulary) and visual skills in addition to phonological skills. Furthermore, early levels of word reading predict the growth of vocabulary knowledge and morphological awareness suggesting that the development of these oral language skills is facilitated by learning to read.

Longitudinal relationships between speech perception, phonological skills and reading in children at high-risk of dyslexia.

Speech perception deficits are commonly reported in dyslexia but longitudinal evidence that poor speech perception compromises learning to read is scant. We assessed the hypothesis that phonological skills, specifically phoneme awareness and RAN, mediate the relationship between speech perception and reading. We assessed longitudinal predictive relationships between categorical speech perception, phoneme awareness, RAN, language, attention and reading at ages 5½ and 6½ years in 237 children many of whom were at high risk of reading difficulties. Speech perception at 5½ years correlated with language, attention, phoneme awareness and RAN concurrently and was a predictor of reading at 6½ years. There was no significant indirect effect of speech perception on reading via phoneme awareness, suggesting that its effects are separable from those of phoneme awareness. Children classified with dyslexia at 8 years had poorer speech perception than age-controls at 5½ years and children with language disorders (with or without dyslexia) had more severe difficulties with both speech perception and attention control. Categorical speech perception tasks tap factors extraneous to perception, including decision-making skills. Further longitudinal studies are needed to unravel the complex relationships between categorical speech perception tasks and measures of reading and language and attention.

Developmental Outcomes for Children at High Risk of Dyslexia and Children With Developmental Language Disorder.

We followed children at family risk of dyslexia and children with preschool language difficulties from age 3½, comparing them with controls (N = 234). At age 8, children were classified as having dyslexia or Developmental Language Disorder (DLD) and compared at earlier time points with controls. Children with dyslexia have specific difficulties with phonology and emergent reading skills in the preschool period, whereas children with DLD, with or without dyslexia, show a wider range of impairments including significant problems with executive and motor tasks. For children with both dyslexia and DLD, difficulties with phonology are generally more severe than those observed in children with dyslexia or DLD alone. Findings confirm that poor phonology is the major cognitive risk factor for dyslexia.

The relationship between numerosity discrimination and arithmetic skill reflects the approximate number system and cannot be explained by inhibitory control.

Numerosity discrimination tasks (judging which of two random dotarrays contains the larger number) have been widely used as a measure of the efficiency of an approximate number system (ANS) and are a correlate of early arithmetic skills. Recently, it has been suggested that the relationship between numerosity discrimination and arithmeticis explained by inhibition rather than the ANS. We assessed this hypothesis in astudy of 496 children (mean age = 81.23 months) using numerosity discrimination tasks that manipulated the congruency between surface area and numerosity. Numerosity discrimination for incongruent arrays (which are postulated to require inhibition due to a conflict between judgments based on surface area rather than numerosity) was more difficult than that for congruent arrays. However, all numerosity discrimination tasks showed substantial correlations with each other and correlated with arithmetic. A latent variable path model showed that a general numerosity judgment factorcorrelated witharithmetic even after controlling for a measure of response inhibition. In contrast, numerosity discrimination for incongruent arrays showed no unique relationship with arithmetic ability. Our results do not support the view that the relationship between numerosity discrimination and arithmetic is largely attributable to inhibition; rather, theyare consistent withthe view that numerosity discrimination tasks tap the operation of an ANS.

Procedural and declarative learning in dyslexia.

The procedural deficit hypothesis claims that impaired procedural learning is at least partly responsible for the deficits in learning to read seen in children with developmental dyslexia. This study used a reading ability-matched design to examine group differences in both procedural and declarative learning. Both children with dyslexia and typically developing children demonstrated procedural learning on a serial reaction time task, although learning in the typically developing group increased at a greater rate towards the end of the task compared with children with dyslexia. However, these results do not provide strong evidence for the procedural deficit hypothesis, because poorer procedural learning in the group with dyslexia may reflect impairments in motor learning, rather than sequence specific procedural learning. In addition, neither group showed a relationship between procedural learning and reading ability.

Improving storytelling and vocabulary in secondary school students with language disorder: a randomized controlled trial.

BACKGROUND: Although language and communication difficulties are common in secondary school students, there has been limited research into the efficacy of interventions for adolescents with language and communication difficulties. AIMS: To investigate the efficacy of teaching assistant (TA)-delivered narrative and vocabulary interventions to mainstream secondary school-aged students with language disorder. METHODS & PROCEDURES: A randomized controlled trial (RCT) of a language and communication intervention was used to evaluate the efficacy of vocabulary and narrative interventions to improve the vocabulary and narrative performance of adolescents (mean age = 12.8 years) with language disorder. The language and communication programmes (narrative, vocabulary and combined narrative and vocabulary) were delivered by TAs in the classroom, three times per week, for 45-60 min each, over 6 weeks, totalling 18 sessions. Standardized and intervention-specific measures were used as outcomes. OUTCOMES & RESULTS: Twenty-one schools with 358 eligible participants were recruited. The three intervention groups showed significant improvements (d = .296) on a narrative latent variable defined by a standardized narrative assessment (the Expression, Reception and Recall of Narrative Instrument-ERRNI), but there were no significant improvements on an overall vocabulary latent variable compared with the waiting control group. Differential effects were found on some non-standardized intervention-specific measures with the narrative group making significantly more progress on narrative tasks compared with the waiting control group, the vocabulary group showing the same pattern on specific vocabulary tasks, and the combined narrative and vocabulary group making significantly more progress on some of the intervention-specific narrative, and all the intervention-specific vocabulary outcomes compared with the waiting control group. CONCLUSIONS & IMPLICATIONS: It is possible to improve narrative but not vocabulary skills, as assessed by standardized measures, in secondary school students with a relatively brief group TA-delivered intervention. There were differential effects for both narrative and vocabulary with intervention-specific measures. Future work is required to explore whether more intensive and longer lasting interventions would be more effective and to identify which students in this age group are most likely to benefit from such interventions.