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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.

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).

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).)

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.)

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.

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).)

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).

Background: This study tests a multiple cognitive deficit model of reading disability (RD), attention-deficit/hyperactivity disorder (ADHD), and their comorbidity., Methods: A structural equation model (SEM) of multiple cognitive risk factors and symptom outcome variables was constructed. The model included phonological awareness as a unique predictor of RD and response inhibition as a unique predictor of ADHD. Processing speed, naming speed, and verbal working memory were modeled as potential shared cognitive deficits., Results: Model fit indices from the SEM indicated satisfactory fit. Closer inspection of the path weights revealed that processing speed was the only cognitive variable with significant unique relationships to RD and ADHD dimensions, particularly inattention. Moreover, the significant correlation between reading and inattention was reduced to non-significance when processing speed was included in the model, suggesting that processing speed primarily accounted for the phenotypic correlation (or comorbidity) between reading and inattention., Conclusions: This study illustrates the power of a multiple deficit approach to complex developmental disorders and psychopathologies, particularly for exploring comorbidities. The theoretical role of processing speed in the developmental pathways of RD and ADHD and directions for future research are discussed., (© 2010 The Authors. Journal of Child Psychology and Psychiatry © 2010 Association for Child and Adolescent Mental Health.)

Moderation of the level of genetic influence on children's high reading ability by environmental influences associated with parental education was explored in two independent samples of identical and fraternal twins from the United States and Great Britain. For both samples, the heritability of high reading performance increased significantly with lower levels of parental education. Thus, resilience (high reading ability despite lower environmental support) is more strongly influenced by genotype than is high reading ability with higher environmental support. This result provides a coherent account when considered alongside results of previous research showing that heritability for low reading ability decreased with lower levels of parental education.

Although a comparison of concordance rates for deviant scores in identical and fraternal twin pairs can provide prima facie evidence for a genetic etiology, information is not fully utilized when continuous measures are analyzed in a dichotomous manner. Thus, DeFries and Fulker (Behav Genet 15:467-473, 1985; Acta Genet Med Gemellol, 37:205-216, 1988) developed a regression-based methodology (DF analysis) to assess genetic etiology in both selected and unselected twin samples. While the DF analysis is a very versatile and relatively powerful statistical approach, it is not easily extended to the multivariate case. In contrast, structural equation models may be readily extended to analyze multivariate data sets (Neale and Cardon, Methodology for genetic studies of twins and families, 1992). However, such methodologies may yield biased estimates of additive genetic, shared environmental, and non-shared environmental influences when multivariate models are fitted to selected twin data. Therefore, the Pearson-Aitken (PA) selection formula (Aitken, Proc Edinburgh Math Soc B, 4:106-110, 1934) was used to analyze reading performance data from twins with reading difficulties (selected sample) and a population of normally-achieving twin pairs (control sample). As a comparison, DF models were also fitted to these same data sets. In general, resulting estimates of additive genetic, shared environmental, and non-shared environmental influences were similar when the DF and PA models were fitted to the data. However, the PA selection formula may be more readily generalized to the multivariate case.

Previous twin studies have suggested a possible developmental dissociation between genetic influences on word recognition and spelling deficits, wherein genetic influence declined across age for word recognition, and increased for spelling recognition. The present study included two measures of word recognition (timed, untimed) and two measures of spelling (recognition, production) in younger and older twins. The heritability estimates for the two word recognition measures were .65 (timed) and .64 (untimed) in the younger group and .65 and .58 respectively in the older group. For spelling, the corresponding estimates were .57 (recognition) and .51 (production) in the younger group and .65 and .67 in the older group. Although these age group differences were not significant, the pattern of decline in heritability across age for reading and increase for spelling conformed to that predicted by the developmental dissociation hypothesis. However, the tests for an interaction between genetic influences on word recognition and spelling deficits as a function of age were not significant.

Background: The study aimed to conduct the first analysis of CAP parent-offspring resemblance for reading performance in children aged 7, 12 and 16 years, and to assess the etiology of individual differences in reading performance of children at 16 years of age., Method: The Reading Recognition subtest of the Peabody Individual Achievement Test was administered to children in the Colorado Adoption Project (CAP) at 7, 12 and 16 years of age, and to their adoptive and nonadoptive parents when the children were 7 years of age., Results: Resulting parent-offspring correlations in adoptive families were not significant at any age, but correlations between scores of nonadoptive control parents and their offspring were significant at all three ages., Conclusions: Results obtained from behavioral genetic model-fitting analyses of data from parents and their children tested at age 16 are consistent with results of studies of twins and siblings indicating that individual differences in reading performance are due substantially to genetic influences. In contrast, environmental transmission from parents to offspring was negligible, suggesting that environmental influences on individual differences in the reading performance of children are largely independent of parental reading performance.

The etiology of the longitudinal stability of reading performance was assessed by analyzing data from adoptive and nonadoptive sibling pairs (206 pairs at age 7, 195 pairs at age 12, and 110 pairs at age 16) tested in the Colorado Adoption Project (CAP). Results of longitudinal behavioral genetic analyses confirmed previous findings of moderate genetic influence on individual differences in reading performance at 7 and 12 years of age (a2 = .44 and .38, respectively), with somewhat higher heritability at age 16 (a2 = .57). Corresponding shared environmental influences were negligible (c2 = .07, .09, and .07). Moreover, common genetic influences were responsible for 66% of the observed stability (rp) between ages 7 and 12 (.62), 62% of that between ages 12 and 16 (rp = .74), and 88% of that between ages 7 and 16 (rp = .55). Of particular interest, no new heritable variation was detected at either 12 or 16 years of age, suggesting that genetic influences at 7 years of age are amplified at the later ages. In contrast, new nonshared environmental influences (including measurement error) were manifested at each age, suggesting the possible importance of nonshared environmental factors (e.g., instructional methods, teachers, peers) for the development of individual differences in reading performance between 7 and 16 years of age.

Objective: To test for brain structure differences in reading disability (RD) by means of MRI-based morphometry., Background: Consensus is lacking on the brain structural correlates of RD. The current study reports on a wider set of structures in the largest sample yet studied, controlling for age, gender, IQ, and attention deficit hyperactivity disorder (ADHD)., Methods: A case-control study was performed that was comprised of 75 individuals with RD (mean age, 17.43+/-4.29 years) and 22 control subjects without RD (mean age, 18.69+/-3.75 years), each a single member of a twin pair. The two groups were similar in age, gender, and handedness, but differed in full-scale IQ (FSIQ), with the RD group having a lower mean FSIQ (101.8+/-9.9 versus 118.3+/-10.3). Using three group-by-structure analyses of covariance, groups were compared in terms of volume (in cubic centimeters) of major neocortical subdivisions, subcortical structures, and midsagittal areas (in square millimeters) of three subdivisions of the corpus callosum., Results: Controlling for age, gender, and IQ, the authors found a significant group-by-structure interaction for the major neocortical subdivisions (p = 0.002), reflecting a different developmental pattern in the RD group, with the insula and anterior superior neocortex being smaller and the retrocallosal cortex being larger in the RD group. In contrast, they found no group main or interaction effects for the subcortical or callosal structures. The pattern of results was essentially the same in subjects without ADHD., Conclusions: Most brain structures do not differ in size in RD, but cortical development is altered subtly. This study replicates in a larger sample previous findings of insular differences in RD and demonstrates further that those differences are not attributable to comorbid ADHD.

The etiology of the observed relationship between reading and mathematics performance was examined by analyzing data from samples of same-sex twin pairs tested in the Colorado Learning Disabilities Research Center. Bivariate phenotypic and genetic structural equation models were fitted to data from 526 twin pairs selected for reading deficits (290 identical and 236 same-sex fraternal) and 355 control pairs (220 identical and 135 same-sex fraternal). Subtests of the Peabody Individual Achievement Test (PIAT; Reading Recognition, Reading Comprehension, and Spelling) were used as measures of reading performance, and scores from the Wechsler Intelligence Scale for Children-Revised (WISC-R) or Wechsler Adult Intelligence Scale-Revised (WAIS-R) Arithmetic subtest, the Wide Range Achievement Test Arithmetic subtest, and the PIAT Math subtest were used as indices for mathematics performance. The results of these confirmatory factor analyses indicate that genetic and environmental covariances between reading and math latent factors do not differ significantly for twin pairs in the proband and control groups. Estimates of heritability for reading performance in the proband and control samples were 0.81 and 0.69, respectively, and those for math performance were 0.88 and 0.67, respectively. Moreover, genetic influences accounted for 83% of the covariation between the reading and math factors in the proband group and for 58% of the covariation between these two latent variables in the control group; in contrast, shared environmental influences did not contribute significantly to the relationship between the reading and math latent factors nor to their independent variation.

This paper reports the results of commingling and genetic segregation analyses performed on a quantitative reading phenotype in 125 families ascertained through normal, nondisabled readers. Commingling analysis using SKUMIX suggested that the reading phenotype best fit a skewed, single distribution model. Complex segregation using POINTER was then performed on the power adjusted data. While there were some analytical ambiguities and complexities, the segregation analysis indicated that there was familial transmission of the phenotype and that a significant percentage of the variance in this phenotype could be attributed to a major gene with dominance. Because the estimated frequency of the putative dominant allele is .35, 57% of the population would carry at least one copy of this allele. This common allele, with low penetrance, accounted for 54% of the phenotypic variance in reading scores. These findings are considered in the context of our earlier report of major gene influence ona qualitative dyslexic phenotype in a sample of 133 dyslexic proband families that were originally matched to the present sample of control families (Pennington et al., 1991). The applicability of a classic single gene, multifactorial-polygenic, and oligogenic or QTL models for reading ability/disability is discussed.

In order to assess the genetic etiology of attention deficit hyperactivity disorder (ADHD), the basic regression model for the analysis of selected twin data (DeFries & Fulker, 1985, 1988) was fitted to questionnaire data (DICA: Diagnostic Interview for Children and Adolescents; Herjanic, Campbell, & Reich, 1982) for 37 identical and 37 fraternal twin pairs tested in the Colorado Reading Project. Results of this analysis suggest that ADHD is highly heritable. Moreover, adjusting DICA scores for either IQ or reading performance differences did not substantially change parameter estimates. In future analyses of larger data sets, distinguishing between possible subtypes of attentional problems (e.g., ADD with or without hyperactivity) may facilitate tests of more searching etiological questions.

Reading and mathematics performance data from a sample of 264 reading-disabled twin pairs and 182 matched control twin pairs were subjected to multivariate behavior genetic analysis. The factor structure of reading and math performance measures was found to be highly similar for both groups. Consistent with previous findings obtained using alternative methods, a significant heritable component to individual differences in reading performance was found both within the reading-disabled (h2 = 0.78) and control (h2 = 0.74) twin samples. In addition, a substantial genetic influence on mathematics performance was found (h2 = 0.51 and 0.60 in the reading-disabled and control samples, respectively), although shared environmental influences common to both members of a twin pair also contribute significantly to the variance in math scores of both groups (c2 = 0.44 and 0.37). Moreover, genetic influences accounted for 98% of the observed correlation between reading and math performance within the sample of reading-disabled twin pairs, and for 55% of the observed correlation in the control sample. Thus, individual differences in both reading and mathematics performance are highly heritable and appear to be caused by many of the same genetic influences.