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Dyslexia and developmental language disorders are important learning difficulties. However, their genetic basis remains poorly understood, and most genetic studies were performed on Europeans. There is a lack of genome-wide association studies (GWAS) on literacy phenotypes of Chinese as a native language and English as a second language (ESL) in a Chinese population. In this study, we conducted GWAS on 34 reading/language-related phenotypes in Hong Kong Chinese bilingual children (including both twins and singletons; total N = 1046). We performed association tests at the single-variant, gene, and pathway levels. In addition, we tested genetic overlap of these phenotypes with other neuropsychiatric disorders, as well as cognitive performance (CP) and educational attainment (EA) using polygenic risk score (PRS) analysis. Totally 5 independent loci (LD-clumped at r 2  = 0.01; MAF > 0.05) reached genome-wide significance (p < 5e-08; filtered by imputation quality metric Rsq>0.3 and having at least 2 correlated SNPs (r 2  > 0.5) with p < 1e-3). The loci were associated with a range of language/literacy traits such as Chinese vocabulary, character and word reading, and rapid digit naming, as well as English lexical decision. Several SNPs from these loci mapped to genes that were reported to be associated with EA and other neuropsychiatric phenotypes, such as MANEA and PLXNC1. In PRS analysis, EA and CP showed the most consistent and significant polygenic overlap with a variety of language traits, especially English literacy skills. To summarize, this study revealed the genetic basis of Chinese and English abilities in a group of Chinese bilingual children. Further studies are warranted to replicate the findings., (© 2024. The Author(s).)

A longstanding cerebral lateralization hypothesis predicts that disrupted development of typical leftward structural asymmetry of auditory cortex explains why children have problems learning to read. Small sample sizes and small effects, potential sex-specific effects, and associations that are limited to specific dimensions of language are thought to have contributed inconsistent results. The large ABCD study dataset (baseline visit: N = 11,859) was used to test the hypothesis of significant associations between surface area asymmetry of auditory cortex and receptive vocabulary performance across boys and girls, as well as an oral word reading effect that was specific to boys. The results provide modest support (Cohen's d effect sizes ≤ 0.10) for the cerebral lateralization hypothesis.

Since almost a hundred years, psychologists have investigated the link between hand preference and dyslexia. We present a meta-analysis to determine whether there is indeed an increase in atypical hand preference in dyslexia. We included studies used in two previous meta-analyses (Bishop, 1990; Eglinton & Annett, 1994) as well as studies identified through PubMed MEDLINE, PsycInfo, Google Scholar, and Web of Science up to August 2022. K = 68 studies (n = 4660 individuals with dyslexia; n = 40845 controls) were entered into three random effects meta-analyses using the odds ratio as the effect size (non-right-handers; left-handers; mixed-handers vs. total). Evidence of elevated levels of atypical hand preference in dyslexia emerged that were especially pronounced for mixed-hand preference (OR = 1.57), although this category was underdefined. Differences in (direction or degree) of hand skill or degree of hand preference could not be assessed as no pertinent studies were located. Our findings allow for robust conclusions only for a relationship of mixed-hand preference with dyslexia., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A recent genome-wide association study on dyslexia in 51,800 affected European adults and 1,087,070 controls detected 42 genome-wide significant single nucleotide variants (SNPs). The association between rs2624839 in SEMA3F and reading fluency was replicated in a Chinese cohort. This study explores the genetic overlap between Chinese and English word reading, vocabulary knowledge and spelling, and aims at replicating the association in a unique cohort of bilingual (Chinese-English) Hong Kong Chinese twins. Our result showed an almost complete genetic overlap in vocabulary knowledge (r 2  = 0.995), and some genetic overlaps in word reading and spelling (r 2  = 0.846, 0.687) across the languages. To investigate the region near rs2624839, we tested proxy SNPs (rs1005678, rs12632110 and rs12494414) at the population level (n = 305-308) and the within-twin level (n = 342-344 [171-172 twin pairs]). All the three SNPs showed significant associations with quantitative Chinese and English vocabulary knowledge (p < 0.05). The strongest association after multiple testing correction was between rs12494414 and English vocabulary knowledge at the within-twin level (p = 0.004). There was a trend of associations with word reading and spelling in English but not in Chinese. Our result suggested that the region near rs2624839 is one of the common genetic factors across English and Chinese vocabulary knowledge and unique factors of English word reading and English spelling in bilingual Chinese twins. A larger sample size is required to validate our findings. Further studies on the relationship between variable expression of SEMA3F, which is important to neurodevelopment, and language and literacy are encouraged., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Visual acuity significantly contributes to quality of life. Deficits in childhood are associated with reading difficulties, which can have detrimental effects on education outcomes. In adults, it has been observed that vision defects such as myopia are associated with higher educational attainment (EA). Understanding genetic factors contributing to visual acuity could help to dissect its links with cognitive skills, neurodevelopmental conditions, and education. We examined associations between distance visual acuity, cognitive measures including school grades, and neurodevelopmental conditions in a longitudinal cohort of British children (ALSPAC, n = 6807, M age = 11.8). We performed a genome-wide association study (GWAS, n = 5571) on visual acuity and tested for genetic associations with relevant phenotypes using polygenic scores (PGS) and genetic correlation analyses. Visual acuity was associated with better cognitive performance and school grades, and reduced in individuals with reading difficulties compared to controls. GWAS revealed genetic associations at the NPLOC4 locus and highlighted other genes involved in sensory function. In line with positive genetic correlations between visual acuity and cognitive measures, EA PGS were positively associated with visual acuity, while there was a less robust negative association with myopia PGS. In conclusion, increased visual acuity is associated with a range of positive outcomes, including better school grades. Our results suggest an association between a higher EA PGS and slightly increased visual acuity in childhood. This could indicate gene-environment correlation, in which environmental exposures linked to higher EA might have detrimental effects on vision offsetting the initial positive effect., (© 2023. The Author(s).)

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.)

Reading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70%, yet few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia., (© 2022. The Author(s).)

Left-right asymmetries in the nervous system (lateralisation) influence a broad range of behaviours, from social responses to navigation and language. The role and pathways of endogenous and environmental mechanisms in the ontogeny of lateralisation remains to be established. The domestic chick is a model of both endogenous and experience-induced lateralisation driven by light exposure. Following the endogenous rightward rotation of the embryo, the asymmetrical position in the egg results in a greater exposure of the right eye to environmental light. To identify the genetic pathways activated by asymmetric light stimulation, and their time course, we exposed embryos to different light regimes: darkness, 6 h of light and 24 h of light. We used RNA-seq to compare gene expression in the right and left retinas and telencephalon. We detected differential gene expression in right vs left retina after 6 h of light exposure. This difference was absent in the darkness condition and had already disappeared by 24 h of light exposure, suggesting that light-induced activation is a self-terminating phenomenon. This transient effect of light exposure was associated with a downregulation of the sensitive-period mediator gene DIO2 (iodothyronine deiodinase 2) in the right retina. No differences between genes expressed in the right vs. left telencephalon were detected. Gene networks associated with lateralisation were connected to vascularisation, cell motility, and the extracellular matrix. Interestingly, we know that the extracellular matrix-including the differentially expressed PDGFRB gene-is involved in morphogenesis, sensitive periods, and in the endogenous chiral mechanism of primary cilia, that drives lateralisation. Our data show a similarity between endogenous and experience-driven lateralisation, identifying functional gene networks that affect lateralisation in a specific time window., (© 2022. The Author(s).)

The aim of our study was to evaluate the benefits of a low-pressure insufflation system (AirSeal) vs. a standard insufflation system in terms of anesthesiologists’ parameters and postoperative pain in patients undergoing laparoscopic surgery for early-stage endometrial cancer. This retrospective study involved five tertiary centers and included 152 patients with apparent early-stage disease who underwent laparoscopic surgical staging with either the low-pressure AirSeal system (8−10 mmHg, n = 84) or standard laparoscopic insufflation (10−12 mmHg, n = 68). All the intraoperative anesthesia variables evaluated (systolic blood pressure, end-tidal CO2, peak airway pressure) were significantly lower in the AirSeal group. We recorded a statistically significant difference between the two groups in the median NRS scores for global pain recorded at 4, 8, and 24 h, and for overall shoulder pain after surgery. Significantly more women in the AirSeal group were also discharged on day one compared to the standard group. All such results were confirmed when analyzing the subgroup of women with a BMI >30 kg/m2. In conclusion, according to our preliminary study, low-pressure laparoscopy represents a valid alternative to standard laparoscopy and could facilitate the development of outpatient surgery.

Handedness is the most commonly investigated lateralised phenotype and is usually measured as a binary left/right category. Its links with psychiatric and neurodevelopmental disorders prompted studies aimed at understanding the underlying genetics, while other measures and side preferences have been less studied. We investigated the heritability of hand, as well as foot, and eye preference by assessing parental effects (n ≤ 5028 family trios) and SNP-based heritability (SNP-h 2 , n ≤ 5931 children) in the Avon Longitudinal Study of Parents and Children (ALSPAC). An independent twin cohort from Hong Kong (n = 358) was used to replicate results from structural equation modelling (SEM). Parental left-side preference increased the chance of an individual to be left-sided for the same trait, with stronger maternal than paternal effects for footedness. By regressing out the effects of sex, age, and ancestry, we transformed laterality categories into quantitative measures. The SNP-h 2 for quantitative handedness and footedness was 0.21 and 0.23, respectively, which is higher than the SNP-h 2 reported in larger genetic studies using binary handedness measures. The heritability of the quantitative measure of handedness increased (0.45) compared to a binary measure for writing hand (0.27) in the Hong Kong twins. Genomic and behavioural SEM identified a shared genetic factor contributing to handedness, footedness, and eyedness, but no independent effects on individual phenotypes. Our analysis demonstrates how quantitative multidimensional laterality phenotypes are better suited to capture the underlying genetics than binary traits., (© 2022. The Author(s).)

Background: In the general population, 10.6% of people favor their left hand over the right for motor tasks. Previous research suggests higher prevalence of atypical (left-, mixed-, or non-right-) handedness in (i) twins compared to singletons, and in (ii) monozygotic compared to dizygotic twins. Moreover, (iii) studies have shown a higher rate of handedness concordance in monozygotic compared to dizygotic twins, in line with genetic factors playing a role for handedness., Methods: By means of a systematic review, we identified 59 studies from previous literature and performed three sets of random effects meta-analyses on (i) twin-to-singleton Odds Ratios (21 studies, n = 189,422 individuals) and (ii) monozygotic-to-dizygotic twin Odds Ratios (48 studies, n = 63,295 individuals), both times for prevalence of left-, mixed-, and non-right-handedness. For monozygotic and dizygotic twin pairs we compared (iii) handedness concordance Odds Ratios (44 studies, n = 36,217 twin pairs). We also tested for potential effects of moderating variables, such as sex, age, the method used to assess handedness, and the twins' zygosity., Results: We found (i) evidence for higher prevalence of left- (Odds Ratio = 1.40, 95% Confidence Interval = [1.26, 1.57]) and non-right- (Odds Ratio = 1.36, 95% Confidence Interval = [1.22, 1.52]), but not mixed-handedness (Odds Ratio = 1.08, 95% Confidence Interval = [0.52, 2.27]) among twins compared to singletons. We further showed a decrease in Odds Ratios in more recent studies (post-1975: Odds Ratio = 1.30, 95% Confidence Interval = [1.17, 1.45]) compared to earlier studies (pre-1975: Odds Ratio = 1.90, 95% Confidence Interval = [1.59-2.27]). While there was (ii) no difference between monozygotic and dizygotic twins regarding prevalence of left- (Odds Ratio = 0.98, 95% Confidence Interval = [0.89, 1.07]), mixed- (Odds Ratio = 0.96, 95% Confidence Interval = [0.46, 1.99]), or non-right-handedness (Odds Ratio = 1.01, 95% Confidence Interval = [0.91, 1.12]), we found that (iii) handedness concordance was elevated among monozygotic compared to dizygotic twin pairs (Odds Ratio = 1.11, 95% Confidence Interval = [1.06, 1.18]). By means of moderator analyses, we did not find evidence for effects of potentially confounding variables., Conclusion: We provide the largest and most comprehensive meta-analysis on handedness in twins. Although a raw, unadjusted analysis found a higher prevalence of left- and non-right-, but not mixed-handedness among twins compared to singletons, left-handedness was substantially more prevalent in earlier than in more recent studies. The single large, recent study which included birth weight, Apgar score and gestational age as covariates found no twin-singleton difference in handedness rate, but these covariates could not be included in the present meta-analysis. Together, the secular shift and the influence of covariates probably make it unsafe to conclude that twinning has a genuine relationship to handedness., (© 2022. The Author(s).)

Following its association with dyslexia in multiple genetic studies, the KIAA0319 gene has been extensively investigated in different animal models but its function in neurodevelopment remains poorly understood. We developed the first human cellular knockout model for KIAA0319 in RPE1 retinal pigment epithelia cells via CRISPR-Cas9n to investigate its role in processes suggested but not confirmed in previous studies, including cilia formation and cell migration. We observed in the KIAA0319 knockout increased cilia length and accelerated cell migration. Using Elastic Resonator Interference Stress Microscopy (ERISM), we detected an increase in cellular force for the knockout cells that was restored by a rescue experiment. Combining ERISM and immunostaining we show that RPE1 cells exert highly dynamic, piconewton vertical pushing forces through actin-rich protrusions that are surrounded by vinculin-rich pulling sites. This protein arrangement and force pattern has previously been associated to podosomes in other cells. KIAA0319 depletion reduces the fraction of cells forming these actin-rich protrusions. Our results suggest an involvement of KIAA0319 in cilia biology and cell-substrate force regulation., (© 2022. The Author(s).)

Dyslexia, a specific reading disability, is a common (up to 10% of children) and highly heritable (~70%) neurodevelopmental disorder. Behavioral and molecular genetic approaches are aimed towards dissecting its significant genetic component. In the proposed review, we will summarize advances in twin and molecular genetic research from the past 20 years. First, we will briefly outline the clinical and educational presentation and epidemiology of dyslexia. Next, we will summarize results from twin studies, followed by molecular genetic research (e.g., genome-wide association studies (GWASs)). In particular, we will highlight converging key insights from genetic research. (1) Dyslexia is a highly polygenic neurodevelopmental disorder with a complex genetic architecture. (2) Dyslexia categories share a large proportion of genetics with continuously distributed measures of reading skills, with shared genetic risks also seen across development. (3) Dyslexia genetic risks are shared with those implicated in many other neurodevelopmental disorders (e.g., developmental language disorder and dyscalculia). Finally, we will discuss the implications and future directions. As the diversity of genetic studies continues to increase through international collaborate efforts, we will highlight the challenges in advances of genetics discoveries in this field.

Increased rates of atypical handedness are observed in neurotypical individuals who are low-performing in mathematical tasks as well as in individuals with special educational needs, such as dyslexia. This is the first investigation of handedness in individuals with Mathematical Learning Difficulties (MLD). We report three new studies ( N  = 134; N  = 1,893; N  = 153) and two sets of meta-analyses (22 studies; N  = 3,667). No difference in atypical hand preference between MLD and Typically Achieving (TA) individuals was found when handedness was assessed with self-report questionnaires, but weak evidence of a difference was found when writing hand was the handedness criterion in Study 1 ( p  = .049). Similarly, when combining data meta-analytically, no hand preference differences were detected. We suggest that: (i) potential handedness effects require larger samples, (ii) direction of hand preference is not a sensitive enough measure of handedness in this context, or that (iii) increased rates of atypical hand preference are not associated with MLD. The latter scenario would suggest that handedness is specifically linked to language-related conditions rather than conditions related to cognitive abilities at large. Future studies need to consider hand skill and degree of hand preference in MLD.