Discovery of 42 genome-wide significant loci associated with dyslexia

Nature Genetics, Год журнала: 2022, Номер 54(11), С. 1621 - 1629

Опубликована: Окт. 20, 2022

Abstract Reading and writing are crucial life skills but roughly one in ten children 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 51,800 adults self-reporting diagnosis 1,087,070 controls identified 42 independent significant loci: 15 genes linked cognitive ability/educational attainment, 27 new potentially more specific dyslexia. We validated 23 loci (13 new) cohorts Chinese European ancestry. Genetic etiology was similar between sexes, covariance with many traits found, including ambidexterity, not neuroanatomical measures language-related circuitry. Dyslexia polygenic scores explained 6% variance reading traits, might future contribute earlier identification remediation

Язык: Английский

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

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(35)

Опубликована: Авг. 23, 2022

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- language-related skills are influenced by genetic variation, with twin-based heritability estimates 30 to 80% depending on the trait. architecture complex, heterogeneous, multifactorial, but investigations contributions single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present multicohort genome-wide association study (GWAS) five traits assessed individually using psychometric measures (word reading, nonword spelling, phoneme awareness, repetition) samples 13,633 33,959 participants aged 5 26 y. identified significant word reading (rs11208009,

Язык: Английский

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Insights into Dyslexia Genetics Research from the Last Two Decades

Brain Sciences, Год журнала: 2021, Номер 12(1), С. 27 - 27

Опубликована: Дек. 26, 2021

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

Язык: Английский

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The Genetic and Molecular Basis of Developmental Language Disorder: A Review

Children, Год журнала: 2022, Номер 9(5), С. 586 - 586

Опубликована: Апрель 20, 2022

Language disorders are highly heritable and influenced by complex interactions between genetic environmental factors. Despite more than twenty years of research, we still lack critical understanding the biological underpinnings language. This review provides an overview landscape developmental language (DLD), with emphasis on importance defining specific features (the phenotype) DLD to inform gene discovery. We phenotype in literature, influence historic variation diagnostic inclusion criteria researchers’ ability compare replicate genotype–phenotype studies. recently identified pathways populations explores current state-of-the-art approaches analysis based hypothesised architecture DLD. will show how recent global efforts unify have vastly increased sample size allow for large multi-cohort metanalyses, leading identification a growing number contributory loci. emphasise important role estimating decipher underlying associations. Finally, explore potential epigenetics further unravel basis disorders.

Язык: Английский

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Towards a dynamic, comprehensive conceptualization of dyslexia

Annals of Dyslexia, Год журнала: 2024, Номер 74(3), С. 303 - 324

Опубликована: Янв. 13, 2024

Here we build from the central strength of existing definition dyslexia-its emphasis on neurobiological origins-and proffer a set seven core principles for new, more comprehensive conceptualization dyslexia. These derive two major research directions: (1) still evolving history attempts to explain dyslexia, including in varied writing systems; and (2) study reading brain circuit, its development, genetic environmental influences. What emerges connecting these directions is dynamic dyslexia that incorporates extensive heterogeneity interdependent contributions multiple biological socio-cultural risk preventive factors. A new therefore, needs transcend both past unitary characterizations assumptions based largely English orthography. Such references ways different languages interact with circuit produce sources failure. Similarly, characteristics consequences have been considered as secondary sequela (e.g., reduced comprehension, social-emotional issues) should be part narrative. Of critical importance, any clarify persisting misconceptions associate lack intelligence, potential learn, or talents. Thus, overall purpose such serve an instrument knowledge enduring reason pursuing growth individual, educator, public.

Язык: Английский

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Knowns and unknowns about the neurobiology of stuttering

PLoS Biology, Год журнала: 2024, Номер 22(2), С. e3002492 - e3002492

Опубликована: Фев. 22, 2024

Stuttering occurs in early childhood during a dynamic phase of brain and behavioral development. The latest studies examining children at ages close to this critical developmental period have identified alterations that are most likely linked stuttering, while spontaneous recovery appears related increased inter-area connectivity. By contrast, therapy-driven improvement adults is associated with functional reorganization within beyond the speech network. etiology however, remains enigmatic. This Unsolved Mystery highlights questions points neuroimaging findings could inspire future research uncover how genetics, interacting neural hierarchies, social context, reward circuitry contribute many facets stuttering.

Язык: Английский

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Causal Relationships Between Screen Use, Reading, and Brain Development in Early Adolescents

Advanced Science, Год журнала: 2024, Номер 11(11)

Опубликована: Янв. 2, 2024

Abstract The rise of new media has greatly changed the lifestyles, leading to increased time on these platforms and less spent reading. This shift particularly profound impacts early adolescents, who are in a critical stage brain development. Previous studies have found associations between screen use mental health, but it remains unclear whether is direct cause outcomes. Here, Adolescent Brain Cognitive Development (ABCD) dataset utlized examine causal relationships results revealed adverse effects language ability specific behaviors while reading positive their volume frontal temporal regions. Interestingly, identified as result, rather than cause, certain such rule‐breaking aggressive behaviors. Furthermore, analysis uncovered an indirect influence use, mediated by changes habits, These findings provide evidence for influences development highlight importance monitoring related habit change children.

Язык: Английский

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Genetic architecture of childhood speech disorder: a review

Molecular Psychiatry, Год журнала: 2024, Номер 29(5), С. 1281 - 1292

Опубликована: Фев. 16, 2024

Abstract Severe speech disorders lead to poor literacy, reduced academic attainment and negative psychosocial outcomes. As early as the 1950s, familial nature of was recognized, implying a genetic basis; but molecular basis remained unknown. In 2001, investigation large three generational family with severe disorder, known childhood apraxia (CAS), revealed first causative gene; FOXP2 . A long hiatus then followed for CAS candidate genes, in past years, analysis cohorts ascertained have over 30 genes. total 36 pathogenic variants been identified from 122 cases across 3 this nascent field. All genes coding regions date, no apparent benefit at stage WGS WES identifying monogenic conditions associated CAS. Hence current findings suggest remarkable one children variant that explains their CAS, significant heterogeneity emerging. Around half are currently supported by medium (6 genes) strong (9 evidence supporting association between gene Despite heterogeneity; many implicated proteins functionally converge on pathways involved chromatin modification or transcriptional regulation, opening door precision diagnosis therapies. Most new previously described neurodevelopmental include intellectual disability, autism epilepsy; broadening phenotypic spectrum distinctly milder presentation defined primary disorder setting normal intellect. Insights into bases severe, rare yet translate understanding heritability more common, typically forms language impairment such stuttering phonological disorder. These likely follow complex inheritance polygenic contributions cases, rather than patterns underly one-third patients Clinical testing should now be implemented individuals given its high diagnostic rate, which parallels other where is already standard care. The shared mechanisms discovery highlight potential targets future

Язык: Английский

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The Musical Abilities, Pleiotropy, Language, and Environment (MAPLE) Framework for Understanding Musicality-Language Links Across the Lifespan

Neurobiology of Language, Год журнала: 2022, Номер 3(4), С. 615 - 664

Опубликована: Янв. 1, 2022

Abstract Using individual differences approaches, a growing body of literature finds positive associations between musicality and language-related abilities, complementing prior findings links musical training language skills. Despite these associations, has been often overlooked in mainstream models acquisition development. To better understand the biological basis differences, we propose Musical Abilities, Pleiotropy, Language, Environment (MAPLE) framework. This novel integrative framework posits that abilities likely share some common genetic architecture (i.e., pleiotropy) addition to degree overlapping neural endophenotypes, influences on musically linguistically enriched environments. Drawing upon recent advances genomic methodologies for unraveling pleiotropy, outline testable predictions future research development how its underlying neurobiological substrates may be supported by pleiotropy with musicality. In support MAPLE framework, review discuss from over seventy behavioral studies, highlighting is robustly associated range speech-language skills required communication These include speech perception-in-noise, prosodic perception, morphosyntactic skills, phonological reading aspects second/foreign learning. Overall, current work provides clear agenda studying musicality-language using an emphasis leveraging genomics complex traits.

Язык: Английский

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Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy

Nature Human Behaviour, Год журнала: 2023, Номер 7(9), С. 1584 - 1600

Опубликована: Июнь 26, 2023

Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex as distinct constructs. We applied the 'pleiotropy-informed' multivariate omnibus statistical test to genome-wide association of 35 measures neuroticism from UK Biobank (n = 336,993). identified 431 significantly associated loci with evidence abundant shared associations, personality domains. Functional characterization implicated genes significant tissue-specific expression in all tested tissues brain-specific gene sets. conditioned independent Big 5 on our findings, boosting discovery other improving polygenic prediction. These findings advance understanding architecture traits, indicating a prominence pleiotropic effects higher order domains such function. Hindley et al. used genetics tools examine underpinnings find they functioning.

Язык: Английский

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