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Although results obtained from recent twin and adoption studies suggest that individual differences in mathematics performance are due in part to heritable influences, no genetic analysis of mathematics disability (MD) has been previously reported. In this article we present data from the first twin sample ascertained for mathematics deficits (40 identical and 23 same-sex fraternal twin pairs in which at least one member had MD). When mathematics performance data from these twin pairs were subjected to a multiple regression analysis, evidence for a significant genetic etiology was obtained. However, tests for the differential etiology of MD as a function of reading performance level were nonsignificant. Results of this first twin study of MD indicate that the condition is significantly heritable, but data from additional twin pairs will be required to test hypotheses of differential etiology more rigorously. [ABSTRACT FROM AUTHOR]

This study investigated the relationship between mathematics difficulties and psychopathology in a large community sample ( N = 881) of youth (8-18 years of age) in the United States. The primary aims of the study were to (a) test the associations between mathematics difficulties and specific components of internalizing, externalizing, attention, and social problems; (b) examine potential age and gender differences; and (c) investigate the longitudinal relationship between mathematics and psychopathology using 5-year follow-up data. Results indicated that individuals with mathematics difficulties exhibited elevations in most dimensions of psychopathology, including anxiety, depression, externalizing behaviors, attention problems, and social problems. Furthermore, mathematics impairment was associated with internalizing problems, rule-breaking behaviors, inattention, and social problems even after controlling for comorbid reading difficulties. Results suggested that the associations between mathematics and psychopathology are generally similar in males and females. Finally, preliminary longitudinal evidence suggested that initial mathematics difficulties predicted elevations of conduct disorder, rule-breaking behavior, inattention, hyperactivity, and social problems at follow-up, with several of these associations remaining significant even after controlling for initial reading. In contrast, there was no significant association between initial mathematics ability and internalizing symptoms at follow-up, demonstrating some amelioration of internalizing symptoms over time.

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).)

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.

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 p T  = 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., (© 2020. The Author(s).)

We conducted whole-genome sequencing of four inbred mouse strains initially selected for high (H1, H2) or low (L1, L2) open-field activity (OFA), and then examined strain distribution patterns for all DNA variants that differed between their BALB/cJ and C57BL/6J parental strains. Next, we assessed genome-wide sharing (3,678,826 variants) both between and within the High and Low Activity strains. Results suggested that about 10% of these DNA variants may be associated with OFA, and clearly demonstrated its polygenic nature. Finally, we conducted bioinformatic analyses of functional genomics data from mouse, rat, and human to refine previously identified quantitative trait loci (QTL) for anxiety-related measures. This combination of sequence analysis and genomic-data integration facilitated refinement of previously intractable QTL findings, and identified possible genes for functional follow-up studies.

This study examined whether strong cognitive skills (i.e. vocabulary, rapid naming, verbal working memory [VWM], and processing speed [PS]) contributed to resilience in single-word reading skills in children at risk for reading difficulties because of low phonological awareness scores (PA). Promotive factors were identified by main effects and protective factors through PA x cognition interactions. This study included 1,807 children ages 8-16. As predicted, all cognitive skills were significantly related to reading, consistent with promotive effects. A significant, but small effect PA x vocabulary interaction (R 2 change=.002, p=.00038) was detected but its form was not consistent with a classic protective effect. Rather, the PA x vocabulary interaction was consistent with a "skill-enhancement" pattern, such that children with strong PA and vocabulary skills had better than expected reading. This study provides a framework for reading resilience research and directs attention to promotive mechanisms underlying reading success., Competing Interests: Conflict of interest statement The authors declare that Lauren M. McGrath and Bruce F. Pennington receive royalties from the textbook, Diagnosing Learning Disorders: From Science into Practice, 3rd Edition from Guilford Press. All other authors declare no conflicts of interest. The findings reported in this manuscript are original, have not been published previously, and have not been simultaneously submitted elsewhere.

The ε4 allele of APOE is a well-established genetic risk factor for cognitive aging and dementia, but its influence on early life cognition is unknown. Consequently, we assessed associations of APOE genotypes with cognitive performance during 7, 12, and 16 year-assessments in our ongoing Colorado Adoption/Twin Study of Lifespan behavioral development (CATSLife). In general, APOE ε4 was associated with lower Verbal, Performance, and Full Scale IQ scores during childhood and adolescence (e.g., Full Scale IQ was lower by 1.91 points per ε4 allele, d = -0.13), with larger effects in females (e.g., average Full Scale IQ scores were 3.41 points lower in females per each ε4 allele vs. 0.33 points lower in males). Thus, these results suggest that deleterious effects of the APOE ε4 allele are manifested before adulthood, especially in females, and support both early origin theories and differential life-course vulnerabilities for later cognitive impairment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Rapid 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., Objective: To identify shared genetic factors that contribute to RAN and RAS performance using a multivariate approach., Methods: We 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., Results: Genome-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 RNLS in the brain, which encodes a catecholamine metabolising protein. Chromatin contact maps of adult hippocampal tissue indicate a potential enhancer-promoter interaction regulating RNLS expression. Neuroimaging genetic analysis in an independent, multiethnic sample (n=690) showed that rs1555839 is associated with structural variation in the right inferior parietal lobule., Conclusion: This 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Current definitions of specific learning disability (SLD) identify a heterogeneous population that includes individuals with weaknesses in reading, math, or writing, and these academic difficulties often co-occur in many of the same individuals. The Colorado Learning Disabilities Research Center (CLDRC) is an interdisciplinary, multisite research program that uses converging levels of analysis to understand the genetic and environmental etiology, neuropsychology, and developmental outcomes of SLDs in reading (RD), math (MD), and writing (WD), along with the comorbidity between these SLDs and other developmental disorders. The latest results from the CLDRC twin study suggest that shared genetic influences contribute to the significant covariance between all aspects of reading (word reading, reading fluency, and reading comprehension) and math (calculations, math fluency, and word problems), and distinct genetic or environmental influences also contribute to weaknesses in each specific academic domain. RD and MD are associated with a range of negative outcomes on both concurrent measures and measures of functional outcomes completed 5 years after the twins were first assessed. Over the next several years the CLDRC will continue to expand on this work by administering a comprehensive test battery that includes measures of all dimensions of academic achievement that are described in current definitions of SLD and incorporating these measures in new neuroimaging and molecular genetic studies., (© 2019 Wiley Periodicals, Inc.)

Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562-3468). We observed a genome-wide significant effect (p < 1 × 10 -8 ) on rapid automatized naming of letters (RANlet) for variants on 18q12.2, within MIR924HG (micro-RNA 924 host gene; rs17663182 p = 4.73 × 10 -9 ), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter; rs16928927, p = 2.25 × 10 -8 ). rs17663182 (18q12.2) also showed genome-wide significant multivariate associations with RAN measures (p = 1.15 × 10 -8 ) and with all the cognitive traits tested (p = 3.07 × 10 -8 ), suggesting (relational) pleiotropic effects of this variant. A polygenic risk score (PRS) analysis revealed significant genetic overlaps of some of the DD-related traits with educational attainment (EDUyears) and ADHD. Reading and spelling abilities were positively associated with EDUyears (p ~ [10 -5 -10 -7 ]) and negatively associated with ADHD PRS (p ~ [10 -8 -10 -17 ]). This corroborates a long-standing hypothesis on the partly shared genetic etiology of DD and ADHD, at the genome-wide level. Our findings suggest new candidate DD susceptibility genes and provide new insights into the genetics of dyslexia and its comorbities.

The present study prospectively evaluated cumulative early life perceived stress in relation to differential change in memory and perceptual speed from middle childhood to early adulthood. We aimed to identify periods of cognitive development susceptible to the effects of perceived stress among both adopted and nonadopted individuals. The sample consisted of participants in the Colorado Adoption Project (CAP, N = 690). Structured latent growth curves were fit to 4 memory outcomes as well as 1 perceptual speed outcome, which described nonlinear change between ages 9 and 30. Both adoption status and cumulative perceived stress indices served as predictors of the latent curves. The perceived stress indices were constructed from the Brooks-Gunn Life Events Scale for Adolescents, and reflected "upsettingness" ratings associated with the occurrence of particular life events during middle childhood (ages 9 to 12) and adolescence (ages 13 to 16). For memory and perceptual speed, cumulative perceived stress did not predict differential cognitive gains. However, differences in perceptual speed trajectories between nonadopted and adopted individuals were observed, with adopted individuals showing smaller gains. Although these findings provide no evidence that emergent variability in memory and perceptual speed trajectories by age 30 are explained by cumulative perceptions of stress in childhood and adolescence, further investigations regarding potential vulnerability across the life span are warranted. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Eleven loci with prior evidence for association with reading and language phenotypes were sequenced in 96 unrelated subjects with significant impairment in reading performance drawn from the Colorado Learning Disability Research Center collection. Out of 148 total individual missense variants identified, the chromosome 7 genes CCDC136 and FLNC contained 19. In addition, a region corresponding to the well-known DYX2 locus for RD contained 74 missense variants. Both allele sets were filtered for a minor allele frequency ≤0.01 and high Polyphen-2 scores. To determine if observations of these alleles are occurring more frequently in our cases than expected by chance in aggregate, counts from our sample were compared to the number of observations in the European subset of the 1000 Genomes Project using Fisher's exact test. Significant P values were achieved for both CCDC136/FLNC (P = 0.0098) and the DYX2 locus (P = 0.012). Taken together, this evidence further supports the influence of these regions on reading performance. These results also support the influence of rare variants in reading disability.

It is now possible to create individual-specific genetic scores, called genome-wide polygenic scores (GPS). We used a GPS for years of education ( EduYears ) to predict reading performance assessed at UK National Curriculum Key Stages 1 (age 7), 2 (age 12) and 3 (age 14) and on reading tests administered at ages 7 and 12 in a UK sample of 5,825 unrelated individuals. EduYears GPS accounts for up to 5% of the variance in reading performance at age 14. GPS predictions remained significant after accounting for general cognitive ability and family socioeconomic status. Reading performance of children in the lowest and highest 12.5% of the EduYears GPS distribution differed by a mean growth in reading ability of approximately two school years. It seems certain that polygenic scores will be used to predict strengths and weaknesses in education.

Background: Males are diagnosed with dyslexia more frequently than females, even in epidemiological samples. This may be explained by greater variance in males' reading performance., Methods: We expand on previous research by rigorously testing the variance difference theory, and testing for mediation of the sex difference by cognitive correlates. We developed an analytic framework that can be applied to group differences in any psychiatric disorder., Results: Males' overrepresentation in the low performance tail of the reading distribution was accounted for by mean and variance differences across sex. There was no sex difference at the high performance tail. Processing speed (PS) and inhibitory control partially mediated the sex difference. Verbal reasoning emerged as a strength in males., Conclusions: Our results complement a previous finding that PS partially mediates the sex difference in symptoms of attention deficit/hyperactivity disorder (ADHD), and helps explain the sex difference in both dyslexia and ADHD and their comorbidity., (© 2017 Association for Child and Adolescent Mental Health.)

Because of recent concerns about the replication of published results in the behavioral and biomedical sciences (Ioannidis, PLoS Medicine, Vol. 2, 2005, p. e124; Open Science Collaboration, Science, Vol. 349, 2015, p. 943; Pashler & Wagenmakers, Perspectives on Psychological Science, Vol. 7, 2012, pp. 528-530), we have conducted a replication of our recently published analyses of longitudinal reading performance and attention deficit-hyperactivity disorder data from twin pairs selected for reading difficulties (Wadsworth et al., Twin Research and Human Genetics, Vol. 18, 2015, pp. 755-761). Results obtained from univariate and bivariate (DeFries & Fulker, Behavior Genetics, Vol. 15, 1985, pp. 467-473; Acta Geneticae Medicae et Gemellologiae: Twin Research, Vol. 37, 1988, pp. 205-216) analyses of data from a subset of twin pairs tested in the International Longitudinal Twin Study of Early Reading Development at post-4th grade, and its continuation into high school at post-9th grade, were compared to those from our previous report. Similar measures of reading performance, the same measures of inattention and hyperactivity/impulsivity, and similar selection criteria were used in the two studies. In general, the patterns of results obtained from these two independent studies were highly similar. Thus, these results clearly illustrate the principle that findings from studies in quantitative behavioral genetics often replicate (Plomin et al., Perspectives on Psychological Science, Vol. 11, 2016, pp. 3-23).

We document the growth in published papers on behavioral genetics for 5-year intervals from 1960 through 2014. We used 1861 papers published in Behavior Genetics to train our search strategy which, when applied to Ovid PsychINFO, selected more than 45,000 publications. Five trends stand out: (1) the number of behavioral genetic publications has grown enormously; nearly 20,000 papers were published in 2010-2014. (2) The number of human quantitative genetic (QG) publications (e.g., twin and adoption studies) has steadily increased with more than 3000 papers published in 2010-2014. (3) The number of human molecular genetic (MG) publications increased substantially from about 2000 in 2000-2004 to 5000 in 2005-2009 to 9000 in 2010-2014. (4) Nonhuman publications yielded similar trends. (5) Although there has been exponential growth in MG publications, both human and nonhuman QG publications continue to grow. A searchable resource of this corpus of behavioral genetic papers is freely available online at http://www.teds.ac.uk/public&#95;datasets.html and will be updated annually., Competing Interests: The authors report no conflict of interest.

Although cross-sectional twin studies have assessed the genetic and environmental etiologies of substance use during adolescence and early adulthood, comparisons of results across different samples, measures, and cohorts are problematic. While several longitudinal twin studies have investigated these issues, few corroborating adoption studies have been conducted. The current study is the first to estimate the magnitude of genetic, shared environmental, and non-shared environmental influences on substance use (cigarettes, alcohol, and marijuana) from ages 14 to 18 years, using a prospective longitudinal adoption design. Adoptive and control sibling correlations provided substantial evidence for early genetic effects on cigarette, alcohol, and marijuana use/no use. Shared environmental effects were relatively modest, except for alcohol use, which showed increases in late adolescence (age 17 to 18 years). Sibling similarity for quantity/frequency of use also support additive genetic influences across adolescence, with some shared environmental influences for all three substances. To test the stability of these influences across time, a series of independent pathway models were run to explore common and age-specific influences. For all substances, there were minimal age-specific additive genetic and shared environmental influences on quantity/frequency of use. Further, there was a trend toward increasing genetic influences on cigarette and alcohol use across ages. Genetic influences on marijuana were important early, but did not contribute substantially at age 17 and 18 years. Overall, the findings indicate that genetic influences make important contributions to the frequency/quantity of substance use in adolescence, and suggest that new genetic influences may emerge in late adolescence for cigarette and alcohol use.

Background: Reading and language skills have overlapping genetic bases, most of which are still unknown. Part of the missing heritability may be caused by copy number variants (CNVs)., Methods: In a dataset of children recruited for a history of reading disability (RD, also known as dyslexia) or attention deficit hyperactivity disorder (ADHD) and their siblings, we investigated the effects of CNVs on reading and language performance. First, we called CNVs with PennCNV using signal intensity data from Illumina OmniExpress arrays (~723,000 probes). Then, we computed the correlation between measures of CNV genomic burden and the first principal component (PC) score derived from several continuous reading and language traits, both before and after adjustment for performance IQ. Finally, we screened the genome, probe-by-probe, for association with the PC scores, through two complementary analyses: we tested a binary CNV state assigned for the location of each probe (i.e., CNV+ or CNV-), and we analyzed continuous probe intensity data using FamCNV., Results: No significant correlation was found between measures of CNV burden and PC scores, and no genome-wide significant associations were detected in probe-by-probe screening. Nominally significant associations were detected (p~10(-2)-10(-3)) within CNTN4 (contactin 4) and CTNNA3 (catenin alpha 3). These genes encode cell adhesion molecules with a likely role in neuronal development, and they have been previously implicated in autism and other neurodevelopmental disorders. A further, targeted assessment of candidate CNV regions revealed associations with the PC score (p~0.026-0.045) within CHRNA7 (cholinergic nicotinic receptor alpha 7), which encodes a ligand-gated ion channel and has also been implicated in neurodevelopmental conditions and language impairment. FamCNV analysis detected a region of association (p~10(-2)-10(-4)) within a frequent deletion ~6 kb downstream of ZNF737 (zinc finger protein 737, uncharacterized protein), which was also observed in the association analysis using CNV calls., Conclusions: These data suggest that CNVs do not underlie a substantial proportion of variance in reading and language skills. Analysis of additional, larger datasets is warranted to further assess the potential effects that we found and to increase the power to detect CNV effects on reading and language.

Although previous research has shown cognitive skills to be important predictors of reading ability in children, the respective roles for genetic and environmental influences on these relations is an open question. The present study explored the genetic and environmental etiologies underlying the relations between selected executive functions and cognitive abilities (working memory, inhibition, processing speed, and naming speed) with 3 components of reading ability (word reading, reading comprehension, and listening comprehension). Twin pairs drawn from the Colorado Front Range (n = 676; 224 monozygotic pairs; 452 dizygotic pairs) between the ages of 8 and 16 (M = 11.11) were assessed on multiple measures of each cognitive and reading-related skill. Each cognitive and reading-related skill was modeled as a latent variable, and behavioral genetic analyses estimated the portions of phenotypic variance on each latent variable due to genetic, shared environmental, and nonshared environmental influences. The covariance between the cognitive skills and reading-related skills was driven primarily by genetic influences. The cognitive skills also shared large amounts of genetic variance, as did the reading-related skills. The common cognitive genetic variance was highly correlated with the common reading genetic variance, suggesting that genetic influences involved in general cognitive processing are also important for reading ability. Skill-specific genetic variance in working memory and processing speed also predicted components of reading ability. Taken together, the present study supports a genetic association between children's cognitive ability and reading ability., ((c) 2016 APA, all rights reserved).)

In the context of current concerns about replication in psychological science, we describe 10 findings from behavioral genetic research that have replicated robustly. These are "big" findings, both in terms of effect size and potential impact on psychological science, such as linearly increasing heritability of intelligence from infancy (20%) through adulthood (60%). Four of our top 10 findings involve the environment, discoveries that could have been found only with genetically sensitive research designs. We also consider reasons specific to behavioral genetics that might explain why these findings replicate., (© The Author(s) 2015.)

Approximately 60% of children with reading difficulties (RD) meet criteria for at least one co-occurring disorder. The most common of these, attention deficit-hyperactivity disorder (ADHD), occurs in 20-40% of individuals with RD. Recent studies have suggested that genetic influences are responsible. To assess the genetic etiologies of RD and the comorbidity of RD and two ADHD symptom dimensions -- inattention (IN) and hyperactivity/impulsivity (H/I) -- we are conducting the first longitudinal twin study of RD and ADHD. Data from twin pairs in which at least one member of the pair met criteria for proband status for RD at initial assessment, and were reassessed 5 years later, were subjected to DeFries-Fulker (DF) analysis. Analyses of reading composite data indicated that over 60% of the proband deficit at initial assessment was due to genetic influences, and that reading deficits at follow-up were due substantially to the same genetic influences. When a bivariate DF model was fitted to reading performance and IN data, genetic influences accounted for 60% of contemporaneous comorbidity and over 60% of the longitudinal relationship. In contrast, analysis of the comorbidity between reading performance and H/I indicated that common genetic influences accounted for only about 20% of the contemporaneous and about 10% of the longitudinal relationships. Results indicate that (1) genetic influences on RD are substantial and highly stable; (2) the comorbidity between RD and IN is due largely to genetic influences, both contemporaneously and longitudinally; and (3) genetic influences contribute significantly less to the comorbidity between RD and H/I.

Background: Males show higher rates of attention deficit hyperactivity disorder (ADHD) than do females. Potential explanations include genuine etiological differences or artifact., Methods: 2,332 twin and sibling youth participated in behavioral and cognitive testing. Partially competing models of symptom severity distribution differences, the mean difference, and variance difference models, were tested within a randomly selected subsample. The Delta method was used to test for mediation of sex differences in ADHD symptom severity by processing speed, inhibition and working memory., Results: The combined mean difference and variance difference models fully explained the sex difference in ADHD symptom severity. Cognitive endophenotypes mediated 14% of the sex difference effect., Conclusions: The sex difference in ADHD symptom severity is valid and may be due to differing genetic and cognitive liabilities between the sexes., (© 2014 Association for Child and Adolescent Mental Health.)

The present study explored the environmental and genetic etiologies of the longitudinal relations between prereading skills and reading and spelling. Twin pairs (n = 489) were assessed before kindergarten (M = 4.9 years), post-first grade (M = 7.4 years), and post-fourth grade (M = 10.4 years). Genetic influences on five prereading skills (print knowledge, rapid naming, phonological awareness, vocabulary, and verbal memory) were primarily responsible for relations with word reading and spelling. However, relations with post-fourth-grade reading comprehension were due to both genetic and shared environmental influences. Genetic and shared environmental influences that were common among the prereading variables covaried with reading and spelling, as did genetic influences unique to verbal memory (only post-fourth-grade comprehension), print knowledge, and rapid naming., (© 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.)

Reading and language abilities are heritable traits that are likely to share some genetic influences with each other. To identify pleiotropic genetic variants affecting these traits, we first performed a genome-wide association scan (GWAS) meta-analysis using three richly characterized datasets comprising individuals with histories of reading or language problems, and their siblings. GWAS was performed in a total of 1862 participants using the first principal component computed from several quantitative measures of reading- and language-related abilities, both before and after adjustment for performance IQ. We identified novel suggestive associations at the SNPs rs59197085 and rs5995177 (uncorrected P ≈ 10(-7) for each SNP), located respectively at the CCDC136/FLNC and RBFOX2 genes. Each of these SNPs then showed evidence for effects across multiple reading and language traits in univariate association testing against the individual traits. FLNC encodes a structural protein involved in cytoskeleton remodelling, while RBFOX2 is an important regulator of alternative splicing in neurons. The CCDC136/FLNC locus showed association with a comparable reading/language measure in an independent sample of 6434 participants from the general population, although involving distinct alleles of the associated SNP. Our datasets will form an important part of on-going international efforts to identify genes contributing to reading and language skills., (© 2014 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)

Reading disability (RD) and language impairment (LI) are common neurodevelopmental disorders with moderately strong genetic components and lifelong implications. RD and LI are marked by unexpected difficulty acquiring and processing written and verbal language, respectively, despite adequate opportunity and instruction. RD and LI-and their associated deficits-are complex, multifactorial, and often comorbid. Genetic studies have repeatedly implicated the DYX2 locus, specifically the genes DCDC2 and KIAA0319, in RD, with recent studies suggesting they also influence LI, verbal language, and cognition. Here, we characterize the relationship of the DYX2 locus with RD, LI, and IQ. To accomplish this, we developed a marker panel densely covering the 1.4 Mb DYX2 locus and assessed association with reading, language, and IQ measures in subjects from the Avon Longitudinal Study of Parents and Children. We then replicated associations in three independent, disorder-selected cohorts. As expected, there were associations with known RD risk genes KIAA0319 and DCDC2. In addition, we implicated markers in or near other DYX2 genes, including TDP2, ACOT13, C6orf62, FAM65B, and CMAHP. However, the LD structure of the locus suggests that associations within TDP2, ACOT13, and C6orf62 are capturing a previously reported risk variant in KIAA0319. Our results further substantiate the candidacy of KIAA0319 and DCDC2 as major effector genes in DYX2, while proposing FAM65B and CMAHP as new DYX2 candidate genes. Association of DYX2 with multiple neurobehavioral traits suggests risk variants have functional consequences affecting multiple neurological processes. Future studies should dissect these functional, possibly interactive relationships of DYX2 candidate genes.

The consequence of reduced cognitive ability from inbreeding has long been investigated, mainly restricted to cousin-cousin marriages. Molecular genetic techniques now allow us to test the relationship between increased ancestral inbreeding and cognitive ability in a population of traditionally unrelated individuals. In a representative UK sample of 2329 individuals, we used genome-wide SNP data to estimate the percentage of the genome covered by runs of homozygous SNPs (ROH). This was tested for association with general cognitive ability, as well as measures of verbal and non-verbal ability. Further, association was tested between these traits and specific ROH. Burden of ROH was not associated with cognitive ability after correction for multiple testing, although burden of ROH was nominally associated with increased non-verbal cognitive ability (P=0.03). Moreover, although no individual ROH was significantly associated with cognitive ability, there was a significant bias towards increased cognitive ability in carriers of ROH (P=0.002). A potential explanation for these results is increased positive assortative mating in spouses with higher cognitive ability, although we found no evidence in support of this hypothesis in a separate sample. Reduced minor allele frequency across the genome was associated with higher cognitive ability, which could contribute to an apparent increase in ROH. This may reflect minor alleles being more likely to be deleterious.

Studies of subtypes of DSM-IV attention-deficit/hyperactivity disorder (ADHD) have provided inconsistent support for the discriminant validity of the combined type (ADHD-C) and predominantly inattentive type (ADHD-I). A large sample of children and adolescents with ADHD (N = 410) and a comparison group without ADHD (N = 311) were used to test the internal and external validity of sluggish cognitive tempo (SCT), a dimension characterized by low energy and sleepy and sluggish behavior. SCT scores were then incorporated in analyses of ADHD subtypes to test whether the discriminant validity of ADHD-C and ADHD-I could be improved by including SCT symptoms as part of the criteria for ADHD-I. Factor analyses of parent and teacher ratings indicated that six SCT items loaded on a factor separate from symptoms of ADHD and other psychopathology, providing important support for the internal validity of SCT. The external validity of SCT was supported by significant associations between SCT and measures of functional impairment and neuropsychological functioning when symptoms of ADHD and other psychopathology were controlled. However, contrary to initial predictions, high levels of SCT did not identify a subgroup of ADHD-I that was clearly distinct from ADHD-C. Instead, the current results suggest that DSM-IV inattention and SCT are separate but correlated symptom dimensions that are each independently associated with important aspects of functional impairment and neuropsychological functioning.

Reading disability (RD) and math disability (MD) frequently co-occur, but the etiology of this comorbidity is not well understood. Groups with RD only (N = 241), MD only (N = 183), and RD + MD (N = 188) and a control group with neither disorder (N = 411) completed a battery of measures of internalizing and externalizing psychopathology, social and academic functioning, and 10 neuropsychological processes. Groups with RD only, MD only, and RD + MD were significantly impaired versus the control group on nearly all measures, and the group with RD + MD was more impaired than the groups with MD and RD alone on measures of internalizing psychopathology, academic functioning, and 7 of 10 neuropsychological constructs. Multiple regression analyses of the neuropsychological measures indicated that deficits in reading and math were associated with shared weaknesses in working memory, processing speed, and verbal comprehension. In contrast, reading difficulties were uniquely associated with weaknesses in phoneme awareness and naming speed, and math deficits were uniquely associated with weaknesses in set shifting. These results support multiple-deficit neuropsychological models of RD and MD and suggest that RD and MD are distinct but related disorders that co-occur because of shared neuropsychological weaknesses in working memory, processing speed, and verbal comprehension.

IQ predicts many measures of life success, as well as trajectories of brain development. Prolonged cortical thickening observed in individuals with high IQ might reflect an extended period of synaptogenesis and high environmental sensitivity or plasticity. We tested this hypothesis by examining the timing of changes in the magnitude of genetic and environmental influences on IQ as a function of IQ score. We found that individuals with high IQ show high environmental influence on IQ into adolescence (resembling younger children), whereas individuals with low IQ show high heritability of IQ in adolescence (resembling adults), a pattern consistent with an extended sensitive period for intellectual development in more-intelligent individuals. The pattern held across a cross-sectional sample of almost 11,000 twin pairs and a longitudinal sample of twins, biological siblings, and adoptive siblings.

Very different neurocognitive processes appear to be involved in cognitive abilities such as verbal and non-verbal ability as compared to learning abilities taught in schools such as reading and mathematics. However, twin studies that compare similarity for monozygotic and dizygotic twins suggest that the same genes are largely responsible for genetic influence on these diverse aspects of cognitive function. It is now possible to test this evidence for strong pleiotropy using DNA alone from samples of unrelated individuals. Here we used this new method with 1.7 million DNA markers for a sample of 2,500 unrelated children at age 12 to investigate for the first time the extent of pleiotropy between general cognitive ability (aka intelligence) and learning abilities (reading, mathematics and language skills). We also compared these DNA results to results from twin analyses using the same sample and measures. The DNA-based method revealed strong genome-wide pleiotropy: Genetic correlations were greater than 0.70 between general cognitive ability and language, reading, and mathematics, results that were highly similar to twin study estimates of genetic correlations. These results indicate that genes related to diverse neurocognitive processes have general rather than specific effects.

This first cross-country twin study of individual differences in reading growth from post-kindergarten to post-second grade analyzed data from 487 twin pairs from the United States, 267 twin pairs from Australia, and 280 twin pairs from Scandinavia. Data from two reading measures were fit to biometric latent growth models. Individual differences for the reading measures at post-kindergarten in the United States and Australia were due primarily to genetic influences and to both genetic and shared environmental influences in Scandinavia. In contrast, individual differences in growth generally had large genetic influences in all countries. These results suggest that genetic influences are largely responsible for individual differences in early reading development. In addition, the timing of the start of formal literacy instruction may affect the etiology of individual differences in early reading development but have only limited influence on the etiology of individual differences in growth., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Identical and fraternal twins (N=540, age 8 to 18 years) were tested on three different measures of writing (Woodcock-Johnson III Tests of Achievement-Writing Samples and Writing Fluency; Handwriting Copy from the Group Diagnostic Reading and Aptitude Achievement Tests), three different language skills (phonological awareness, rapid naming, and vocabulary), and three different reading skills (word recognition, spelling, and reading comprehension). Substantial genetic influence was found on two of the writing measures, writing samples and handwriting copy, and all of the language and reading measures. Shared environment influences were generally not significant, except for Vocabulary. Non-shared environment estimates, including measurement error, were significant for all variables. Genetic influences among the writing measures were significantly correlated (highest between the speeded measures writing fluency and handwriting copy), but there were also significant independent genetic influences between copy and samples and between fluency and samples. Genetic influences on writing were significantly correlated with genetic influences on all of the language and reading skills, but significant independent genetic influences were also found for copy and samples, whose genetic correlations were significantly less than 1.0 with the reading and language skills. The genetic correlations varied significantly in strength depending on the overlap between the writing, language, and reading task demands. We discuss implications of our results for education, limitations of the study, and new directions for research on writing and its relations to language and reading.

This first Japanese twin study of early literacy development investigated the extent to which genetic and environmental factors influence individual differences in prereading skills in 238 pairs of twins at 42 months of age. Twin pairs were individually tested on measures of phonological awareness, kana letter name/sound knowledge, receptive vocabulary, visual perception, nonword repetition, and digit span. Results obtained from univariate behavioral-genetic analyses yielded little evidence for genetic influences, but substantial shared-environmental influences, for all measures. Phenotypic confirmatory factor analysis suggested three correlated factors: phonological awareness, letter name/sound knowledge, and general prereading skills. Multivariate behavioral genetic analyses confirmed relatively small genetic and substantial shared environmental influences on the factors. The correlations among the three factors were mostly attributable to shared environment. Thus, shared environmental influences play an important role in the early reading development of Japanese children.

We explored the etiology of individual differences in reading development from post-kindergarten to post-4 th grade by analyzing data from 487 twin pairs tested in Colorado. Data from three reading measures and one spelling measure were fit to biometric latent growth curve models, allowing us to extend previous behavioral genetic studies of the etiology of early reading development at specific time points. We found primarily genetic influences on individual differences at post-1 st grade for all measures. Genetic influences on variance in growth rates were also found, with evidence of small, nonsignificant, shared environmental influences for two measures. We discuss our results, including their implications for educational policy.

This paper describes the Colorado Adoption Project (CAP), a longitudinal study in behavioral development, and discusses how adoption studies may be used to assess genetic and environmental etiologies of individual differences for important developmental outcomes. Previous CAP research on adjustment outcomes in childhood and adolescence which found significant interactions, including gene-environment interactions, is reviewed. New research suggests mediating effects of menarche and religiosity on age at first sex in this predominantly middle-class, Caucasian sample.

The present study explored whether different executive control and speed measures (working memory, inhibition, processing speed, and naming speed) independently predict individual differences in word reading and reading comprehension. Although previous studies suggest these cognitive constructs are important for reading, the authors analyze the constructs simultaneously to test whether each is a unique predictor. Latent variables from 483 participants (ages 8-16 years) were used to portion each cognitive and reading construct into its unique and shared variance. In these models 2 specific issues are addressed: (a) Given that the wide age range may span the theoretical transition from "learning to read" to "reading to learn," the authors first test whether the relation between word reading and reading comprehension is stable across 2 age groups (ages 8-10 and 11-16); and (b) the main theoretical question of interest: whether what is shared and what is separable for word reading and reading comprehension are associated with individual differences in working memory, inhibition, and measures of processing and naming speed. The results indicated that (a) the relation between word reading and reading comprehension is largely invariant across the age groups, and (b) working memory and general processing speed, but not inhibition or the speeded naming of non-alphanumeric stimuli, are unique predictors of both word reading and comprehension, with working memory equally important for both reading abilities and processing speed more important for word reading. These results have implications for understanding why reading comprehension and word reading are highly correlated yet separable, (. (PsycINFO Database Record (c) 2012 APA, all rights reserved).)

Reading performance data from 254 pairs of identical (MZ) and 420 pairs of fraternal (DZ) twins, 8.0 to 20.0 years of age, were subjected to multiple regression analyses. An extension of the DeFries-Fulker (DF) analysis (DeFries & Fulker, 1985, 1988) that facilitated inclusion of data from 303 of their nontwin siblings was employed. In addition to providing estimates of heritability, this analysis yields a test of the difference between shared environmental influences for twins versus siblings (Astrom et al., 2011). Results suggest that proband reading deficits are due substantially to genetic factors (.67 ± .07, p < .001), and that shared environmental influences are significantly higher for members of twin pairs than for those of twins and their nontwin siblings (viz., .25 versus .17, p = .02).

The augmented multiple regression model for the analysis of data from selected twin pairs was extended to facilitate analyses of data from twin pairs and nontwin siblings. Fitting this extended model to data from both selected twin pairs and siblings yields direct estimates of heritability (h2) and the difference between environmental influences shared by members of twin pairs and those of sib or twin-sib pairs (i.e., c2(t) - c2 (s)). When this model was fitted to reading performance data from 293 monozygotic and 436 dizygotic pairs selected for reading difficulties, and 291 of their nontwin siblings, h2 = .48 ± .22, p = .03, and c2 (t) - c2 (s) = .22 ± .12, p = .06. Although the test for differential shared environmental influences is only marginally significant, the results of this analysis suggest that environmental influences on reading performance that are shared by members of twin pairs (.36) may be substantially greater than those for less contemporaneous twin-sibling pairs (.14).

Reading difficulties are both heritable and stable; however, little is known about the etiology of this stability. Results from a preliminary analysis of data from 56 twin pairs who participated in the Colorado Longitudinal Twin Study of Reading Disability (Astrom et al., Twin Res Hum Genet 10:434-439, 2007) suggested that about two-thirds of the proband deficit at follow-up was due to genetic factors that also influenced deficits at their initial assessment. Although our proband sample is now nearly twice as large, it is still relatively small; thus, to increase power, we subjected data from probands, co-twins and their nontwin siblings to a novel extension of DeFries-Fulker analysis (DeFries and Fulker, Behav Genet 15:467-473, 1985; DeFries and Fulker, Acta Genet Med Gemellol, 37, 205-216, 1988). In addition to providing estimates of univariate and bivariate heritability, this analysis facilitates a test of the difference between shared environmental influences for twins versus siblings. Longitudinal composite reading performance scores at 10.6 and 15.5 years of age, on average, were analyzed from 33 MZ and 64 DZ twin pairs in which at least one member of each pair had reading difficulties, and from 44 siblings of the probands. Scores were highly stable (.86 ± .03, across probands, co-twins and siblings) and heritability of the group deficit at initial assessment was .67 ± .22. Longitudinal bivariate heritability was .59 ± .21, suggesting that nearly 60% of the proband reading deficit at follow-up is due to genetic factors that influenced reading difficulties at the initial assessment. However, tests for special twin environmental influences were nonsignificant.

This study evaluated the internal structure and convergent and discriminant evidence for the Colorado Learning Difficulties Questionnaire (CLDQ), a 20-item parent-report rating scale that was developed to provide a brief screening measure for learning difficulties. CLDQ ratings were obtained from parents of children in 2 large community samples and 2 samples from clinics that specialize in the assessment of learning disabilities and related disorders (total N = 8,004). Exploratory and confirmatory factor analyses revealed 5 correlated but separable dimensions that were labeled reading, math, social cognition, social anxiety, and spatial difficulties. Results revealed strong convergent and discriminant evidence for the CLDQ Reading scale, suggesting that this scale may provide a useful method to screen for reading difficulties in both research studies and clinical settings. Results are also promising for the other 4 CLDQ scales, but additional research is needed to refine each of these measures.