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.

Expectation Modulates Repetition Suppression at Late But Not Early Stages during Visual Word Recognition: Evidence from Event-related Potentials.

Visual word recognition is commonly rapid and efficient, incorporating top-down predictive processing mechanisms. Neuroimaging studies with face stimuli suggest that repetition suppression (RS) reflects predictive processing at the neural level, as this effect is larger when repetitions are more frequent, that is, more expected. It remains unclear, however, at the temporal level whether and how RS and its modulation by expectation occur in visual word recognition. To address this gap, the present study aimed to investigate the presence and time course of these effects during visual word recognition using EEG. Thirty-six native Cantonese speakers were presented with pairs of Chinese written words and performed a nonlinguistic oddball task. The second word of a pair was either a repetition of the first or a different word (alternation). In repetition blocks, 75% of trials were repetitions and 25% were alternations, whereas the reverse was true in alternation blocks. Topographic analysis of variance of EEG at each time point showed robust RS effects in three time windows (141-227 msec, 242-445 msec, and 467-513 msec) reflecting facilitation of visual word recognition. Importantly, the modulation of RS by expectation was observed at the late rather than early intervals (334-387 msec, 465-550 msec, and 559-632 msec) and more than 100 msec after the first RS effects. In the predictive coding view of RS, only late repetition effects are modulated by expectation, whereas early RS effects may be mediated by lower-level predictions. Taken together, our findings provide the first EEG evidence revealing distinct temporal dynamics of RS effects and repetition probability on RS effects in visual processing of Chinese words.

Dyslexia-related loci are significantly associated with language and literacy in Chinese-English bilingual Hong Kong Chinese twins.

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 (r2 = 0.995), and some genetic overlaps in word reading and spelling (r2 = 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.

Repetition Suppression for Familiar Visual Words Through Acceleration of Early Processing.

The visual N1 (N170) component with occipito-temporal negativity and fronto-central positivity is sensitive to visual expertise for print. Slightly later, an N200 component with an increase after stimulus repetition was reported to be specific for Chinese, but found at centro-parietal electrodes against a mastoid reference. Given the unusual location, temporal proximity to the N1, and atypical repetition behavior, we aimed at clarifying the relation between the two components. We collected 128-channel EEG data from 18 native Chinese readers during a script decision experiment. Familiar Chinese one- and two-character words were presented among unfamiliar Korean control stimuli with half of the stimuli immediately repeated. Stimulus repetition led to a focal increase in the N1 onset and to a wide-spread decrease in the N1 offset, especially for familiar Chinese and also prominently near the mastoids. A TANOVA analysis corroborated robust repetition effects in the N1 offset across ERP maps with a modulation by script familiarity around 300 ms. Microstate analyses revealed a shorter N1 microstate duration after repetitions, especially for Chinese. The results demonstrate that the previously reported centro-parietal N200 effects after repetitions reflect changes during the N1 offset at occipito-temporal electrodes including the mastoids. Although larger for Chinese, repetition effects could also be found for two-character Korean words, suggesting that they are not specific for Chinese. While the decrease of the N1 offset after repetition is in agreement with a repetition suppression effect, the microstate findings suggest that at least part of the facilitation is due to accelerated processing after repetition.

Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia.

Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40-60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10-6) enrichment of associations at the gene level, for LOC388780 (20p13; uncharacterized gene), and for VEPH1 (3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20-25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (at pT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase; p = 8 × 10-13), bipolar disorder (1.53[1.44; 1.63]; p = 1 × 10-43), schizophrenia (1.36[1.28; 1.45]; p = 4 × 10-22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30]; p = 3 × 10-12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96]; p = 5 × 10-4), educational attainment (0.86[0.82; 0.91]; p = 2 × 10-7), and intelligence (0.72[0.68; 0.76]; p = 9 × 10-29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.

Development of neural specialization for print: Evidence for predictive coding in visual word recognition.

How a child's brain develops specialization for print is poorly understood. One longstanding account is selective neuronal tuning to regularity of visual-orthographic features, which predicts a monotonically increased neural activation for inputs with higher regularity during development. However, we observed a robust interaction between a stimulus' orthographic regularity (bottom-up input) and children's lexical classification ability (top-down prediction): N1 response, which is the first negative component of the event-related potential (ERP) occurring at posterior electrodes, was stronger to lower-regularity stimuli, but only in children who were less efficient in lexically classifying these stimuli (high prediction error). In contrast, N1 responses were reduced to lower-regularity stimuli in children who showed high efficiency of lexical classification (low prediction error). The modulation of children's lexical classification efficiency on their neural responses to orthographic stimuli supports the predictive coding account of neural processes of reading.

Electroencephalography decoding of Chinese characters in primary school children and its prediction for word reading performance and development.

Research on what neural mechanisms facilitate word reading development in non-alphabetic scripts is relatively rare. The present study was among the first to adopt a multivariate pattern classification analysis to decode electroencephalographic signals recorded for primary school children (N = 236) while performing a Chinese character decision task. Chinese is an ideal script for studying the relationship between neural discriminability (i.e., decodability) of the orthography and behavioral word reading skills since the mapping from orthography to phonology is relatively arbitrary in Chinese. This was also among the first empirical attempts to examine the extent to which decoding performance can predict current and subsequent word reading skills using a longitudinal design. Results showed that neural activation patterns of real characters can be distinguished from activation patterns for pseudo-characters, non-characters, and random stroke combinations in both younger and older children. Topography of the transformed classifier weights revealed two distinct cognitive sub-processes underlying single character recognition, but temporal generalization analysis suggested common neural mechanisms between the distinct cognitive sub-processes. Suggestive evidence from correlational and hierarchical regression analyses showed that decoding performance, assessed on average 2 months before the year 2 behavioral testing, predicted both year 1 word reading performance and the development of word reading fluency over the year. Results demonstrate that decoding performance, one indicator of how the neural system is functionally organized in processing characters and character-like stimuli, can serve as a useful neural marker in predicting current word reading skills and the capacity to learn to read.

Remediation of a phonological representation deficit in Chinese children with dyslexia: A comparison between metalinguistic training and working memory training.

A form-preparation task in the language production field was adopted to examine output phonological representations in Chinese dyslexia and their susceptibility to training. Forty-one Chinese children with dyslexia (7-11 years old) and 36 chronological age controls completed this task. The controls demonstrated a marginally significant syllable facilitation effect (d = -0.13), indicating their use of syllable-sized phonological representations during speech production, while the group with dyslexia showed a significantly different pattern (d = 0.04), opposite to the direction of a facilitation effect. The children with dyslexia were then randomly assigned to either metalinguistic training (N = 22) or working memory training (N = 19). Only the metalinguistic training subgroup demonstrated a significant syllable facilitation effect afterward (metalinguistic: d = -0.13; working memory: d = -0.01). The results suggest the presence of a phonological representation deficit at the syllable level in Chinese dyslexia and its possible remediation by metalinguistic training. Such a phonological deficit in readers of a logographic script strongly supports the impaired phonological representation view of developmental dyslexia. A video abstract of this article can be viewed at https://youtu.be/zT2Be0xMkh0.

Event-related potentials during Chinese single-character and two-character word reading in children.

Word reading involves a series of cognitive processes, from lower-level visual processing to word semantic retrieval. To investigate the timing of the underlying neurocognitive processes in reading, the current study examined the electrophysiological correlates of cognitive functions associated with traditional Chinese word reading in Hong Kong children (Age: M = 8.19, SD = 0.82 years old) using event-related potentials (ERPs). A single-character lexical decision task and a two-character word lexical decision task were used to explore different levels of Chinese word processing. One-hundred ten children's data were analyzed. Results revealed that radical level processing was related to a P1 component at as early as 130 ms. Character-level processing was related to an N1 component from 218 ms onwards. Two-character word semantic processing was related to an N400-like component at as early as 450 ms. The results show a similar time course of visual word processing as previously reported in alphabetic languages, consistent with increasing specialization in the ventral visual stream for increasing wordlikeness leading to processing of linguistic aspects in higher-level language regions.

Neural Processes Associated with Vocabulary and Vowel-Length Differences in a Dialect: An ERP Study in Pre-literate Children.

Although familiarity with a language impacts how phonology and semantics are processed at the neural level, little is known how these processes are affected by familiarity with a dialect. By measuring event-related potentials (ERPs) in kindergarten children we investigated neural processing related to familiarity with dialect-specific pronunciation and lexicality of spoken words before literacy acquisition in school. Children speaking one of two German dialects were presented with spoken word-picture pairings, in which congruity (or the lack thereof) was defined by dialect familiarity with pronunciation or vocabulary. In a dialect-independent control contrast, congruity was defined by audio-visual semantic (mis)match. Congruity effects and congruity-by-dialect group interactions in the ERPs were tested by data-driven topographic analyses of variance (TANOVA) and theory-driven focal analyses. Converging results revealed similar congruity effects in the N400 and late-positive-complex (LPC) in the control contrast for both dialect groups. In the dialect-specific vocabulary contrast, topographies of the N400- and LPC-effects were reversed depending on familiarity with the presented dialect words. In the dialect-specific pronunciation contrast, again a topography reversal was found depending on dialect familiarity, however, only for the LPC. Our data suggest that neural processing of unfamiliar words, but not pronunciation variants, is characterized by semantic processing (increased N400-effect). However, both unfamiliar words and pronunciation variants seem to engage congruity judgment, as indicated by the LPC-effect. Thus, semantic processing of pronunciation in dialect words seems to be rather robust against slight alterations in pronunciation, like changes in vowel duration, while such alterations may still trigger subsequent control processes.

Neurocognitive mechanisms of learning to read: print tuning in beginning readers related to word-reading fluency and semantics but not phonology.

During reading acquisition children learn to recognize orthographic stimuli and link them to phonology and semantics. The present study investigated neurocognitive processes of learning to read after one year of schooling. We aimed to elucidate the cognitive processes underlying neural tuning for print that has been shown to play an important role for reading and dyslexia. A 128-channel EEG was recorded while 68 (Swiss-)German monolingual first grade children (mean age: 7.6) performed a one-back task with different types of letter and false-font strings. Print tuning was indexed by the N1 difference in the ERPs between German words and false-font strings, while the N1 lexicality effect was indexed by the difference between German words and pseudowords. In addition, we measured reading fluency, rapid automatized naming, phonological awareness, auditory memory span, and vocabulary. After one year of formal reading instruction N1 print tuning was clearly present at the group level, and could be detected at the individual level in almost 90% of the children. The N1 lexicality effect, however, could not be reliably found. On the cognitive level, next to word-reading fluency, vocabulary was also associated with N1 print tuning, but not measures reflecting phonological processing. These results demonstrate the presence of print tuning in the first year of reading acquisition and its development at the individual level. Moreover, individual differences in print tuning are not only related to word-reading fluency, but also to semantic knowledge, indicating that at early stages of learning to read the top-down modulation of print tuning is semantic rather than phonological in nature.

Frontal midline theta reflects individual task performance in a working memory task.

Frontal midline (fm-)theta activity has been related to working memory (WM) processes, as it typically increases with WM load. The robustness of this effect, however, varies across studies and subjects, putting limits to its interpretation. We hypothesized that variation in the fm-theta effect may reflect individual differences in task difficulty with increasing WM load as indicated by behavioural responses. We further tested whether effects in the alpha range are robust markers of WM load. We recorded 64-channel EEG from 24 healthy adults while they memorized either 2 or 4 unfamiliar symbols (low vs. high WM load) in a modified Sternberg task. The last 2 s of the retention phase were analyzed for WM load-related changes in the theta (5-7 Hz) and alpha range (lower: 8-10 Hz, upper: 10.5-12.5 Hz). Higher WM load led to less accurate and slower responses. The increase of fm-theta with WM load was most pronounced at fm electrodes, localized to anterior cingulate regions, and correlated with the participants' decrease in accuracy due to higher WM load. Alpha peak frequency increased in the high compared to the low WM load condition, corresponding to a decrease in lower alpha range across all channels. The results demonstrate that previously reported variation in fm-theta workload effects can partly be explained by variation in task difficulty indexed by individual task accuracy. Moreover, the results also demonstrate that alpha WM load effects are prominent when separating upper and lower alpha.

Gene-environment interaction on neural mechanisms of orthographic processing in Chinese children.

The ability to process and identify visual words requires efficient orthographic processing of print, consisting of letters in alphabetic languages or characters in Chinese. The N170 is a robust neural marker for orthographic processes. Both genetic and environmental factors, such as home literacy, have been shown to influence orthographic processing at the behavioral level, but their relative contributions and interactions are not well understood. The present study aimed to reveal possible gene-by-environment interactions on orthographic processing at the behavioral and neural level in a normal children sample. Sixty 12 year old Chinese children from a 10-year longitudinal sample underwent an implicit visual-word color decision task on real words and stroke combinations. The ERP analysis focused on the increase of the occipito-temporal N170 to words compared to stroke combinations. The genetic analysis focused on two SNPs (rs1419228, rs1091047) in the gene DCDC2 based on previous findings linking these 2 SNPs to orthographic coding. Home literacy was measured previously as the number of children's books at home, when the children were at the age of 3. Relative to stroke combinations, real words evoked greater N170 in bilateral posterior brain regions. A significant interaction between rs1091047 and home literacy was observed on the changes of N170 comparing real words to stroke combinations in the left hemisphere. Particularly, children carrying the major allele "G" showed a similar N170 effect irrespective of their environment, while children carrying the minor allele "C" showed a smaller N170 effect in low home-literacy environment than those in good environment.

Fine neural tuning for orthographic properties of words emerges early in children reading alphabetic script.

The left-lateralized N170 component of ERPs for words compared with various control stimuli is considered as an electrophysiological manifestation of visual expertise for written words. To understand the information sensitivity of the effect, researchers distinguish between coarse tuning for words (the N170 amplitude difference between words and symbol strings) and fine tuning for words (the N170 amplitude difference between words and consonant strings). Earlier developmental ERP studies demonstrated that the coarse tuning for words occurred early in children (8 years old), whereas the fine tuning for words emerged much later (10 years old). Given that there are large individual differences in reading ability in young children, these tuning effects may emerge earlier than expected in some children. This study measured N170 responses to words and control stimuli in a large group of 7-year-olds that varied widely in reading ability. In both low and high reading ability groups, we observed the coarse neural tuning for words. More interestingly, we found that a stronger N170 for words than consonant strings emerged in children with high but not low reading ability. Our study demonstrates for the first time that fine neural tuning for orthographic properties of words can be observed in young children with high reading ability, suggesting that the emergent age of this effect is much earlier than previously assumed. The modulation of this effect by reading ability suggests that fine tuning is flexible and highly related to experience. Moreover, we found a correlation between this tuning effect at left occipitotemporal electrodes and children's reading ability, suggesting that the fine tuning might be a biomarker of reading skills at the very beginning of learning to read.

Selective attention to phonology dynamically modulates initial encoding of auditory words within the left hemisphere.

Selective attention to phonology, i.e., the ability to attend to sub-syllabic units within spoken words, is a critical precursor to literacy acquisition. Recent functional magnetic resonance imaging evidence has demonstrated that a left-lateralized network of frontal, temporal, and posterior language regions, including the visual word form area, supports this skill. The current event-related potential (ERP) study investigated the temporal dynamics of selective attention to phonology during spoken word perception. We tested the hypothesis that selective attention to phonology dynamically modulates stimulus encoding by recruiting left-lateralized processes specifically while the information critical for performance is unfolding. Selective attention to phonology was captured by manipulating listening goals: skilled adult readers attended to either rhyme or melody within auditory stimulus pairs. Each pair superimposed rhyming and melodic information ensuring identical sensory stimulation. Selective attention to phonology produced distinct early and late topographic ERP effects during stimulus encoding. Data-driven source localization analyses revealed that selective attention to phonology led to significantly greater recruitment of left-lateralized posterior and extensive temporal regions, which was notably concurrent with the rhyme-relevant information within the word. Furthermore, selective attention effects were specific to auditory stimulus encoding and not observed in response to cues, arguing against the notion that they reflect sustained task setting. Collectively, these results demonstrate that selective attention to phonology dynamically engages a left-lateralized network during the critical time-period of perception for achieving phonological analysis goals. These findings suggest a key role for selective attention in on-line phonological computations. Furthermore, these findings motivate future research on the role that neural mechanisms of attention may play in phonological awareness impairments thought to underlie developmental reading disabilities.

Integration of spoken and written words in beginning readers: a topographic ERP study.

Integrating visual and auditory language information is critical for reading. Suppression and congruency effects in audiovisual paradigms with letters and speech sounds have provided information about low-level mechanisms of grapheme-phoneme integration during reading. However, the central question about how such processes relate to reading entire words remains unexplored. Using ERPs, we investigated whether audiovisual integration occurs for words already in beginning readers, and if so, whether this integration is reflected by differences in map strength or topography (aim 1); and moreover, whether such integration is associated with reading fluency (aim 2). A 128-channel EEG was recorded while 69 monolingual (Swiss)-German speaking first-graders performed a detection task with rare targets. Stimuli were presented in blocks either auditorily (A), visually (V) or audiovisually (matching: AVM; nonmatching: AVN). Corresponding ERPs were computed, and unimodal ERPs summated (A + V = sumAV). We applied TANOVAs to identify time windows with significant integration effects: suppression (sumAV-AVM) and congruency (AVN-AVM). They were further characterized using GFP and 3D-centroid analyses, and significant effects were correlated with reading fluency. The results suggest that audiovisual suppression effects occur for familiar German and unfamiliar English words, whereas audiovisual congruency effects can be found only for familiar German words, probably due to lexical-semantic processes involved. Moreover, congruency effects were characterized by topographic differences, indicating that different sources are active during processing of congruent compared to incongruent audiovisual words. Furthermore, no clear associations between audiovisual integration and reading fluency were found. The degree to which such associations develop in beginning readers remains open to further investigation.

Neural mechanism underlying preview effects and masked priming effects in visual word processing.

Two classic experimental paradigms - masked repetition priming and the boundary paradigm - have played a pivotal role in understanding the process of visual word recognition. Traditionally, these paradigms have been employed by different communities of researchers, with their own long-standing research traditions. Nevertheless, a review of the literature suggests that the brain-electric correlates of word processing established with both paradigms may show interesting similarities, in particular with regard to the location, timing, and direction of N1 and N250 effects. However, as of yet, no direct comparison has been undertaken between the two paradigms. In the current study, we used combined eye-tracking/EEG to perform such a within-subject comparison using the same materials (single Chinese characters) as stimuli. To facilitate direct comparisons, we used a simplified version of the boundary paradigm - the single word boundary paradigm. Our results show the typical early repetition effects of N1 and N250 for both paradigms. However, repetition effects in N250 (i.e., a reduced negativity following identical-word primes/previews as compared to different-word primes/previews) were larger with the single word boundary paradigm than with masked priming. For N1 effects, repetition effects were similar across the two paradigms, showing a larger N1 after repetitions as compared to alternations. Therefore, the results indicate that at the neural level, a briefly presented and masked foveal prime produces qualitatively similar facilitatory effects on visual word recognition as a parafoveal preview before a single saccade, although such effects appear to be stronger in the latter case.

Development of EEG alpha and theta oscillations in the maintenance stage of working memory.

Several studies have shown developmental changes in EEG oscillations during working memory tasks. Although the load-modulated theta and alpha activities in adults are well-documented, the findings are inconsistent if children possess the adult-like brain oscillations that are similarly modulated by memory load. The present study compares children's and adults' true theta and alpha EEG oscillations, separated from aperiodic components, in the maintenance stage of working memory. The EEG was recorded in 25 Chinese-speaking children (14 male, Mage = 9.4 yrs) and 31 adults (19 male, Mage = 20.8 yrs) in Hong Kong while they performed an n-back task that included four conditions differing in load (1- vs. 2-back) and stimulus type (Chinese character vs. visual pattern). The results show that aperiodic activities (i.e., broadband power and slope) during the maintenance stage in the n-back task were significantly higher in children than adults. The periodic theta and alpha oscillations also changed with age. More importantly, adults showed significant periodic theta increase with memory load, whereas such an effect was absent in children. Regardless of age, there was a significant alpha power decrease with load increase, and a significant theta power enhancement when maintaining visual patterns than Chinese characters. In adults, load-modulated alpha peak shift (towards higher frequency) was linked to higher behavioral efficiency in the n-back task. In children, higher load-modulated theta enhancement was linked to better behavioral efficiency. The findings suggest that the load-modulated theta power during working memory maintenance matures from childhood to adulthood.

A genome-wide association study of Chinese and English language phenotypes in Hong Kong Chinese children.

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 r2 = 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 (r2 > 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.

Visual print tuning deficits in dyslexic adolescents under minimized phonological demands.

The left ventral occipitotemporal cortex is reliably activated by visual orthographic stimulation and has repeatedly been found underactivated in developmental dyslexia. However, previous studies have made little effort to specifically probe orthographic processing while minimizing the need for higher-order reading related operations, especially phonological processing. Phonological deficits are well documented in dyslexia but may limit interpretations of ventral occipitotemporal underactivation as a primarily orthographic coding deficit, considering that different processing modes occur highly parallel. We therefore used a task that restricts higher-order processing to better isolate orthographic deficits. Thirteen dyslexic adolescents and twenty-two matched typical readers performed a low-level target detection task combined with rapidly presented stimuli of increasing similarity to real words during functional magnetic resonance imaging. The clear deviance found in impaired readers' left ventral occipitotemporal organization suggested deficits in print sensitivity at bottom-up processing stages that are largely independent of phonological operations. This finding elucidates print processing during a critical developmental transition from child- to adulthood and extends current accounts on left ventral occipitotemporal functionality.