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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.

Objective: Predictive validity is a fundamental consideration in evaluating the DSM-IV diagnostic criteria for attention deficit hyperactivity disorder (ADHD), particularly for younger children. Method: The authors conducted four annual assessments of ADHD and functional impairment using multiple informants in 255 probands and matched comparison children who were 4-6 years old in wave 1. Results: Nearly all children who met full criteria for ADHD in wave 1 met full criteria for ADHD over the next 3 years and continued to display marked functional impairment relative to comparison children, even when intelligence, co-occurring psychopathology, and demographic characteristics were controlled. Conclusions: These findings support the validity of the DSM-IV diagnosis of ADHD in younger children by demonstrating that the symptoms and associated impairment are likely to persist well into elementary school.

The article highlights a study which found that psychometric testing has not yet revealed the central cognitive deficits underlying Sluggish Cognitive Tempo (SCT).

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.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is diagnosed when symptoms begin in childhood. We investigated whether individuals diagnosed as children differ from those diagnosed in adulthood with respect to shared and unique architecture at the genome-wide and gene expression level of analysis.

BackgroundRapid automatised naming (RAN) and rapid alternating stimulus (RAS) are reliable predictors of reading disability. The underlying biology of reading disability is poorly understood. However, the high correlation among RAN, RAS and reading could be attributable to shared genetic factors that contribute to common biological mechanisms.ObjectiveTo identify shared genetic factors that contribute to RAN and RAS performance using a multivariate approach.MethodsWe conducted a multivariate genome-wide association analysis of RAN Objects, RAN Letters and RAS Letters/Numbers in a sample of 1331 Hispanic American and African–American youth. Follow-up neuroimaging genetic analysis of cortical regions associated with reading ability in an independent sample and epigenetic examination of extant data predicting tissue-specific functionality in the brain were also conducted.ResultsGenome-wide significant effects were observed at rs1555839 (p=4.03×10−8) and replicated in an independent sample of 318 children of European ancestry. Epigenetic analysis and chromatin state models of the implicated 70 kb region of 10q23.31 support active transcription of the gene RNLSin the brain, which encodes a catecholamine metabolising protein. Chromatin contact maps of adult hippocampal tissue indicate a potential enhancer–promoter interaction regulating RNLSexpression. Neuroimaging genetic analysis in an independent, multiethnic sample (n=690) showed that rs1555839 is associated with structural variation in the right inferior parietal lobule.ConclusionThis study provides support for a novel trait locus at chromosome 10q23.31 and proposes a potential gene–brain–behaviour relationship for targeted future functional analysis to understand underlying biological mechanisms for reading disability.

The present study investigated the relation among reading skills and attributions, naming speed, and phonological awareness across a wide range of reading skill. Participants were 1,105 school‐age children and youths from two understudied populations: African Americans and Hispanic Americans. Individual assessments of children ranging in age from 8 to 15 years were conducted for reading outcomes, cognitive and linguistic predictors of reading, and attributions for success and failure in reading situations. Quantile regressions were formulated to estimate these relations across the full skill span of each outcome. Reading‐related attributions predicted contextual word recognition, sight word and decoding fluency, and comprehension skills. Attributions to ability in success situations were positively related to each outcome across the full span. On three reading outcomes, this relation strengthened at higher skill levels. Attributions to effort in success situations were consistently and negatively related to all reading outcomes. The results provide evidence that the strength of the relation between reading and attributions varies according to reading skill levels, with the strongest evidence for ability‐based attributions in situations of reading success. 本研究在一个涵盖广阔阅读技能范围中,探讨阅读技能与成败归因、命名速度以及语音意识之间的关系。研究参与者来自1,105名美国非洲裔和西班牙裔学龄儿童及青少年,有关该两个人种群体的研究并不多。年龄介乎8至15岁的学龄儿童接受阅读成果、预测阅读的认知和语言,以及在各种阅读情况下的成败归因等方面的个别评估。研究人员制订了分位数回归模型,用以估计涵盖所有技能跨度内的每一项成果中这些关系。与阅读有关的成败归因能预测语境词识别能力、读出不用拼讀解碼的单字能力和解码流畅度,以及阅读理解技能。在成功的情况下,归因于能力对所有跨度内的每一项成果都呈正相关。有三个阅读成果显示出这种关系在较高技能水平上得到加强。在成功的情况下,归因于努力对所有阅读成果则一致地呈负相关。这些研究结果提供证据显示,阅读与成败归因之关系的强弱,是随阅读技能水平的高低而有所不同,而在阅读成功的情况下,基于能力归因的证据最为有力。 El presente estudio investigó la relación entre las destrezas y atribuciones lectoras, la rapidez de nombramiento, y la conciencia fonológica a través de una gama amplia de destrezas lectoras. Los participantes fueron 1,105 niños y jóvenes en edad escolar de dos poblaciones poco estudiadas: americanos africanos y americanos hispanos. Las evaluaciones individuales de niños entre los 8 y 15 años fueron conducidas para resultados de lectura, predictores de lectura cognoscitivos y lingüísticos, y atribuciones para el éxito o fracaso en situaciones de lectura. Se crearon regresiones de cuartil para estimar dichas relaciones a través de la gama completa de destrezas de cada resultado. Atribuciones relacionadas con la lectura predijeron el reconocimiento contextual de palabras, la fluidez de descifrar palabras a la vista, y las destrezas de comprensión. Las atribuciones a la capacidad de tener éxito fueron relacionadas positivamente a cada resultado a través de la gama completa. En tres resultados de lectura, dicha relación mostró ser más fuerte a niveles más altos de destrezas. Las atribuciones al esfuerzo en situaciones de éxito fueron relacionadas consistente y negativamente a todos los resultados. Los resultados sirven de evidencia de que la fuerza de la relación entre la lectura y las atribuciones varía de acuerdo al nivel de destrezas de lectura, con la evidencia más fuerte para las atribuciones basadas en destrezas en las situaciones de éxito en la lectura. حققت هذه الدراسة العلاقة بين مهارات القراءة والصفات ، وسرعة التسمية، والوعي الصوتي عبر مجموعة واسعة من مهارات القراءة. وكان المشاركون 1،105 طفل في سن الدراسة والشباب من اثنين من جمعات السكان الغير مدروسة: الأمريكيين من أصل أفريقي والأميركيين من أصل اسباني. وأجريت تقييمات فردية للأطفال التي تتراوح أعمارهم من 8 إلى 15 سنة لنتائج القراءة، وتنبئات القراءة المعرفية واللغوية ، وصفات النجاح والفشل في حالات القراءة. صيغت انحدارات كوانتيل (Quantile) لتقدير هذه العلاقات عبر امتداد المهارات الكاملة لكل نتيجة. توقعت الصفات ذات الصلة بالقراءة سياقية التعرف على الكلمات، والطلاقة في التعرف على الكلمات وفك التشفير، ومهارات الفهم. نسبة الصفات إلى القدرة في حالات النجاح كانت بشكل إيجابي لكل نتيجة عبر الفترة كاملة. على نتائج القراءة الثلاث ، تعززت هذه العلاقة في مستويات المهارة العالية. نسبة الصفات إلى الجهد في حالات النجاح تعلقت باستمرار وبشكل سلبي على جميع نتائج القراءة. توفر النتائج دليل على أن قوة العلاقة بين القراءة والصفات تختلف وفقا لمستوى مهارة القراءة، مع أقوى دليل للصفات على أساس القدرة في حالات نجاح القراءة. Ученых заинтересовали взаимосвязи между широким диапазоном различных читательских навыков и такими параметрами, как скорость и фонологическое понимание. В исследовании участвовали 1105 детей и подростков из двух плохо изученных диаспор: афроамериканцы и испаноязычные американцы. Для каждого ребенка от 8 до 15 лет определили результаты чтения, познавательные и лингвистические предикторы, а также маркеры успешности и неуспешности в ситуации чтения. Квантильная регрессия дала возможность оценить взаимосвязь между навыками и параметрами чтения при всех возможных результатов. Можно предсказать узнавание слова из контекста, опознание слова на вид, скорость его декодирования и навыки понимания. В ситуациях с успешным чтением результаты всецело зависят от способностей, причем эта связь только усиливается на более высоких уровнях читательской компетентности. Обратная картина наблюдается в ситуациях успешного чтения для усилий: от них ничего не зависит. Результаты свидетельствуют о том, что крепость связей между качеством чтения и различными его параметрами меняется в зависимости от уровня читательской компетентности, причем доказано, что читательский успех самым прямым образом связан со способностями. Cette recherche porte sur les relations entre les compétences en lecture et les attributions, la vitesse de dénomination, la conscience phonologique pour une vaste gamme de compétences en lecture. Les participants étaient 1.105 enfants et adolescents d’âge scolaire originaires de deux populations peu étudiées : les Afro‐américains et les Hispano‐américains. Nous avons évalué les résultats en lecture d’élèves de 8 à 15 ans, des prédicteurs cognitifs et linguistiques de la lecture, et des attributions de succès et d’échec dans des situations de lecture. Nous avons effectué des régressions par quantiles pour estimer ces relations sur tout l'empan des compétences avec chaque résultat. Les attributions relatives à la lecture prédisent la reconnaissance de mots en contexte, la lecture globale de mots, la rapidité de décodage, et les compétences de compréhension. Les attributions relatives aux situations avec réussite sont positivement corrélées avec chaque résultat pour tout l'empan. Pour trois résultats de lecture, cette corrélation est encore plus forte avec les niveaux de compétence plus élevés. Les attributions à l'effort dans les situations de réussite sont de façon constante corrélées négativement à tous les résultats en lecture. Ces résultats montrent que la force de la relation entre la lecture et les attributions varie selon les niveaux de compétence en lecture, les résultats les plus solides concernant les attributions basées sur les compétences avec les situations de réussite en lecture.

Attention-deficit/hyperactivity disorder (ADHD) and reading disability (RD) are complex childhood disorders that frequently co-occur, but the etiology of this comorbidity remains unknown.

Family and twin studies suggest that a range of neurocognitive traits index the inherited liability to ADHD; however, the utility of such measures as endophenotypes in molecular genetic studies remains largely untested. The current article examined whether the inclusion of neurocognitive measures in a genomewide linkage analysis of ADHD could aid in identifying QTL linked to the behavioral symptoms of the condition. Data were from an affected sibling pair linkage study of DSMIV ADHD conducted at Massachusetts General Hospital. The sample included 1,212 individuals from 271 families. ADHD symptoms were assessed with the KSADSE. The neurocognitive battery included Wechsler Intelligence Scales subtests, the Stroop, the Wisconsin Card Sorting Test WCST, the ReyOsterreith Complex Figure, a working memory CPT, the CVLT and WRATIII subscales. Evidence for linkage was assessed using a simulationbased method that combines information from univariate analyses into the equivalent of a multivariate test. After correction for multiple trait testing, a region on chromosome 3q13 showed suggestive linkage to all neurocognitive traits examined and inattention symptoms of ADHD. The second highest peak occurred on 22q12 but showed linkage to a single subscale of the WCST. In univariate analysis, this region retained criteria for suggestive linkage to this measure after correction for multiple trait testing. Our primary findings raise the possibility that one or more genes on 3q13 influence neurocognitive functions and behavioral symptoms of inattention. Overall, these data support the utility of neurocognitive traits as ADHD endophenotypes, but also highlight their limited genetic overlap with the disorder. © 2008 WileyLiss, Inc.

A community sample of twins in which at least one member of each pair exhibited significant reading difficulties (99 monozygotic and 80 dizygotic pairs) or symptoms of attention‐deficit/hyperactivity disorder (ADHD; 83 monozygotic and 78 dizygotic pairs) was used to test the etiology of comorbidity between reading disability (RD) and ADHD. Univariate analyses revealed moderate to high heritability for all measures of reading difficulty and ADHD. Subsequent bivariate analyses indicated that the relation between reading difficulties and inattention symptoms is primarily attributable to common genetic influences, whereas bivariate heritability estimates were not significant for hyperactivity‐impulsivity and any of the reading measures. Reading difficulties and ADHD symptoms were more highly heritable if the proband met criteria for both disorders versus RD or ADHD alone, suggesting that future molecular genetic analyses of comorbid RD + ADHD may facilitate the identification of susceptibility genes for RD, ADHD, and their comorbidity. © 2007 Wiley‐Liss, Inc.

The present research sought to test the validity of the non-random mating hypothesis in a community sample in order to determine whether it contributes significantly to the comorbidity between attention-deficit/hyperactivity disorder (ADHD) and reading disability (RD) and to test whether the two disorders segregate independently. Data were gathered from 394 twin participants of the Colorado Learning Disabilities Research Center (CLDRC) and their biological parents. Parents were asked to complete retrospective questionnaires regarding their own ADHD and RD symptomatology as children, as well as rate their children on DSM-IV ADHD symptomatology before age 12. Twin RD was assessed by a composite score consisting of several reading measures. Chi-square and correlational analyses assessed the presence of non-random mating, as well as whether the two disorders were transmitted independently. Non-random mating between those with ADHD and those with RD did not significantly contribute to the comorbidity of the two disorders. Furthermore, there was some evidence that these two disorders did not segregate independently in this sample. These results are consistent with recent evidence that ADHD and RD are often comorbid because of significant genetic overlap. There was little evidence to support that non-random mating also contributes to this comorbidity in the present sample. © 2003 Wiley-Liss, Inc.

Comorbidity is pervasive among both adult and child psychiatric disorders; however, the etiological mechanisms underlying the majority of comorbidities are unknown. This study used genetic linkage analysis to assess the etiology of comorbidity between reading disability (RD) and attention-deficit hyperactivity disorder (ADHD), two common childhood disorders that frequently co-occur. Sibling pairs (N = 85) were ascertained initially because at least one individual in each pair exhibited a history of reading difficulties. Univariate linkage analyses in sibling pairs selected for ADHD from within this RD-ascertained sample suggested that a quantitative trait locus (QTL) on chromosome 6p is a susceptibility locus for ADHD. Because this QTL is in the same region as a well-replicated QTL for reading disability, subsequent bivariate analyses were conducted to test if this QTL contributed to comorbidity between the two disorders. Analyses of data from sib pairs selected for reading deficits revealed suggestive bivariate linkage for ADHD and three measures of reading difficulty, indicating that comorbidity between RD and ADHD may be due at least in part to pleiotropic effects of a QTL on chromosome 6p. © 2002 Wiley-Liss, Inc.

The article focuses on external and internal validity of Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV subtypes of attention-deficit hyperactivity disorder (ADHD). Results of a study conducted in 357 children show that high test-retest correlations between hyperactive symptoms and DSM-IV inattention has an average of 18 months apart. Results of study for external validity show that the ADHD/IA and ADHD/C subtypes have lower measures of mathematics and reading than ADHD/HI.

This study utilized a sample of 313 eight- to sixteen-year-old same-sex twin pairs (183 monozygotic, 130 dizygotic) to assess the etiology of comorbidity between reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD). RD was assessed by a discriminant function score based on the Peabody Individual Achievement Test, a standardized measure of academic achievement. The DSM-III version of the Diagnostic Interview for Children and Adolescents was used to assess symptoms of ADHD, and separate factor scores were computed for inattention and hyperactivity/impulsivity (hyp/imp). Individuals with RD were significantly more likely than individuals without RD to exhibit elevations on both symptom dimensions, but the difference was larger for inattention than hyp/imp. Behavior genetic analyses indicated that the bivariate heritability of RD and inattention was significant (h²g(RD/Inatt) = 0.39), whereas the bivariate heritability of RD and hyp/imp was minimal and nonsignificant (h²g(RD/Hyp) = 0.05). Approximately 95% of the phenotypic covariance between RD and symptoms of inattention was attributable to common genetic influences, whereas only 21% of the phenotypic overlap between RD and hyp/imp was due to the same genetic factors. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:293–301, 2000. © 2000 Wiley-Liss, Inc.

The University of California, Irvine ADD Center recently conducted a synthesis of the literature on the use of stimulants with children with attention deficit disorder (ADD), using a unique “review of reviews” methodology. In this article, we compare three reviews from each of three review types (traditional, meta-analytic, general audience) and illustrate how coding variables can highlight sources of divergence. In general, divergent conclusions stemmed from variations in goal rather than from variations in the sources selected to review. Across quantitative reviews, the average effect size for symptomatic improvement (.83) was twice that for benefits on IQ and achievement measures (.35). A summary of what shouldand should notbe expected of the use of stimulants with ADD children, derived from the literature synthesis, is provided.

No Abstract.