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ObjectiveTo investigate the genetic architecture of internalizing symptoms in childhood and adolescence.MethodIn 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument.ResultsThe meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg| = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa.ConclusionGenetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

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.

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.

Background: Current physical activity guidelines may be insufficient to address health consequences in a world increasing in sedentary behavior. Physical activity is a key lifestyle factor to promote healthy aging, but few studies examine activity in conjunction with sitting. We examine how activity intensity and sitting behavior influence health and the extent to which physical activity might counter sitting. Methods: We analyzed data from the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife) in adults aged 28–49 years (M = 33.16, SD = 4.93). We fit a linear mixed-effect model for body mass index (BMI) and total cholesterol/high-density lipoprotein ratio (TC/HDL). Leveraging the co-twin control approach, we explore the trade-off between sitting and physical activity. Results: Across established adulthood, TC/HDL and BMI demonstrated increasing age trends with prolonged sitting and vigorous activity inversely associated. Moreover, after considering sitting time, we found an age-equivalent benefit of vigorous exercise where those performing 30 minutes daily had expected TC/HDL and BMI estimates that mirrored sedentary individuals 5 and 10 years younger, respectively. Co-twin control analysis suggests partial exposure effects for TC/HDL, indicating greater vigorous activity may counter sitting-health effects but with diminishing returns. Conclusions: Our findings support the counteracting influence of prolonged sitting and physical activity on indicators of cardiovascular and metabolic health. A compensating role of vigorous activity on sitting health links is indicated while reducing sitting time appears paramount. Public health initiatives should consider sitting and vigorous activity in tandem in guidelines to promote health maintenance and combat accelerated aging. [ABSTRACT FROM AUTHOR]

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.

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.

Limited evidence supports the external validity of the distinction between developmental phonological and surface dyslexia. We previously identified children ages 8 to 13 meeting criteria for these subtypes (Peterson, Pennington, & Olson, 2013) and now report on their reading and related skills approximately 5 years later. Longitudinal stability of subtype membership was fair and appeared stronger for phonological than surface dyslexia. Phonological dyslexia was associated with a pronounced phonological awareness deficit, but subgroups otherwise had similar cognitive profiles. Subtype did not inform prognosis. Results provide modest evidence for the validity of the distinction, although not for its clinical utility.

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. (Contains 7 tables and 1 figure.)

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 nonalphanumeric 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. (Contains 5 tables, 6 figures and 5 footnotes.)

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 (0.67 [plus or minus] 0.07, p less than 0.001), and that shared environmental influences are significantly higher for members of twin pairs than for those of twins and their nontwin siblings (viz., 0.25 versus 0.17, p = 0.02). (Contains 2 tables and 2 figures.)

Genetic and environmental relations between vocabulary and reading skills were explored longitudinally from preschool through Grades 2 and 4. At preschool there were strong shared-environment and weak genetic influences on both vocabulary and print knowledge but substantial differences in their source. Separation of etiology for vocabulary and reading continued for word recognition and decoding through Grade 4, but genetic and environmental correlations between vocabulary and reading comprehension approached unity by Grade 4, when vocabulary and word recognition accounted for all of the genetic and shared environment influences on reading comprehension. (Contains 7 tables.)

It is often assumed that differences in teacher characteristics are a major source of variability in children's educational achievements. We examine this assumption for early literacy achievement by calculating the correlations between pairs of twin children who either shared or did not share a teacher in kindergarten, Grade 1, and Grade 2. Teacher effects--or, more strictly, classroom effects--would show up as higher correlations for same-class than for different-class twin pairs. Same-class correlations were generally higher than different-class correlations, though not significantly so on most occasions. On the basis of the results, we estimate that the maximum variance accounted for by being assigned to the same or different classrooms is 8%. This is an upper-bound figure for a teacher effect because factors other than teachers may contribute to variation attributable to classroom assignment. We discuss the limitations of the study and draw out some of its educational implications. (Contains 3 tables. )

Individual differences in word recognition, spelling, and reading comprehension for 324 children at a mean age of 16 were predicted from their reading-related skills (phoneme awareness, phonological decoding, rapid naming, and IQ) at a mean age of 10 years, after controlling the predictors for the autoregressive effects of the correlated reading skills. There were significant and longitudinally stable individual differences for all four reading-related skills that were independent from each of the reading and spelling skills. Yet the only significant longitudinal prediction of reading skills was from IQ at mean age 10 for reading comprehension at mean age 16. The extremely high longitudinal latent-trait stability correlations for individual differences in word recognition (0.98) and spelling (0.95) left little independent outcome variance that could be predicted by the reading-related skills. We discuss the practical and theoretical importance of these results and why they differ from studies of younger children. (Contains 6 tables and 2 figures.)

The prevalence of reading difficulties is typically higher in males than females in both referred and research-identified samples, and the ratio of males to females is greater in more affected samples. To explore possible gender differences in reading performance, we analysed data from 1133 twin pairs in which at least one member of each pair had a school history of reading problems and from 684 twin pairs from a comparison sample with no reading difficulties. Although the difference between the average scores of males and females in these two samples was very small, the variance of reading performance was significantly greater for males in both groups. We suggest that a greater variance of reading performance measures in males may account at least in part for their higher prevalence of reading difficulties as well as for the higher gender ratios that are observed in more severely impaired samples. (Contains 1 figure.)

The primary objectives of the present study are to introduce the Colorado Longitudinal Twin Study of Reading Disability, the first longitudinal twin study in which subjects have been specifically selected for having a history of reading difficulties, and to present some initial assessments of the stability of reading performance and cognitive abilities in this sample. Preliminary examination of the test scores of 124 twins with a history of reading difficulties and 154 twins with no history of reading difficulties indicates that over the 5- to 6-year interval between assessments, cognitive and reading performance are highly stable. As a group, those subjects with a history of reading difficulties had substantial deficits relative to control subjects on all measures at initial assessment, and significant deficits remained at follow-up. The stability noted for all cognitive and achievement measures was highest for a composite measure of reading, whose average stability correlation across groups was 0.80. Results of preliminary behavior genetic analyses for this measure indicated that shared genetic influences accounted for 86% and 49% of the phenotypic correlations between the two assessments for twin pairs with and without reading difficulties, respectively. In addition, genetic correlations reached unity for both groups, suggesting that the same genetic influences are manifested at both time points.

Numerous studies have examined the etiology of the association between reading difficulties and attention-deficit hyperactivity disorder (ADHD) in school-age children, but little is known about the relation between prereading skills and ADHD behaviors prior to the beginning of formal reading instruction. A population-based sample of 809 pairs of preschool twins completed an extensive battery of prereading measures, and the parent of each twin completed an ADHD rating scale. Phenotypic analyses revealed small but significant correlations between DSM-IV inattention ratings and six prereading composite measures, whereas hyperactivity-impulsivity symptoms were not independently associated with any of the prereading scores. Multivariate twin analyses indicated that virtually all of the phenotypic correlation between inattention and prereading performance is attributable to common genetic influences, consistent with results obtained in studies of older twins. Although additional research is needed to test alternative causal models in children younger than five years old, these results are most consistent with the hypothesis that reading difficulties and inattention symptoms are attributable to common genetic influences.

To test the hypothesis that the etiology of reading difficulties may differ for males and females in more severely impaired samples, reading performance data from monozygotic (MZ), same-sex dizygotic (DZ[subscript ss]), and opposite-sex dizygotic (DZ[subscript os]) twin pairs were analyzed using a model-fitting implementation of the DeFries-Fulker (DF) model (Purcell & Sham, 2003, "Behavior genetics", 33, 271-278). Five non-independent samples were selected using cut-offs of -1 (N = 737 pairs), -1.5 (N = 654), -2 (N = 468), -2.5 (N = 335), and -3 (N = 198) standard deviations (s) below the mean composite reading score of control twins. Male/female gender ratios for children with reading difficulties were significantly higher than 1.0 for all five samples and increased as a function of severity (viz., 1.15, 1.17, 1.40, 1.61, and 1.88, respectively). When the DF model was fit to the data, estimates of heritability (h[subscript g [squared]] ) and shared environmental influences (c[subscript g [squared]] ) were not significantly different for males and females in any of the groups. Consequently, the most parsimonious model that provided a good fit to the data at all five levels of severity equated the heritabilities and shared environmental influences for males and females, and fixed the DZ[subscript os] coefficient of genetic relatedness at 0.5. Thus, these results provide no evidence for a differential etiology of reading difficulties as a function of gender in more severely impaired samples, and suggest that the same genetic and environmental influences contribute to reading difficulties in males and females, irrespective of severity.

To test the hypothesis that the genetic etiology for reading disability may differ in males and females, data from identical and fraternal twin pairs were analysed using both concordance and multiple regression methods. The sample included 264 identical (129 male, 135 female) and 214 same-sex fraternal (121 male, 93 female) twin pairs in which at least one member of each pair had reading difficulties. The difference between the identical and fraternal twin pair concordance rates was slightly larger for females than for males, suggesting a possible sex difference in etiology; however, a loglinear analysis of the three-way interaction of sex, zygosity, and concordance was not significant (p greater than or equal to 0.17). The estimate of group heritability (h[subscript g][superscript 2]), a standardized measure of the extent to which reading difficulties are due to genetic influences, was somewhat greater for females than males (0.65 vs 0.54), but this difference was also not significant (p greater than or equal to 0.35). Gender differences in h[subscript g][superscript 2] were larger for younger children (less than 11.5 years of age) than for older children. However, the three-way interaction of sex, zygosity, and age was not significant when age was treated either categorically (p greater than or equal to 0.86) or continuously (p greater than or equal to 0.71). Thus, results of this study provide little or no evidence for a differential genetic etiology of reading difficulties in males and females. (Contains 3 tables.)

We report preliminary behaviour genetic analyses of reading and listening comprehension from The Colorado Learning Disabilities Research Center. Although the twin sample with these new measures is still of limited size, we find substantial, and significant, genetic influences on individual differences in both reading and listening comprehension. In addition, word recognition and listening comprehension each accounted for significant "independent" genetic influences on reading comprehension. Together, they accounted for "all" the genetic influence on reading comprehension, indicating a largely genetic basis for the "simple model" of individual differences in reading comprehension proposed by Hoover and Gough (1990).

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. [ABSTRACT FROM AUTHOR]

Analyzes composition reading performance data from identical and fraternal twin pairs in order to test the hypothesis that genetic influences are more important as a cause of reading disability in girls than in boys. Provides little or no evidence for the hypothesis of greater genetic influence on reading difficulties in girls than in boys. (SC)

Composite reading performance data from 223 pairs of identical twins and 169 same-gender fraternal twins in which at least one member was classified with reading disability were subjected to multiple regression analysis. Results indicated that the genetic etiology of reading disability differs as a linear function of IQ. (Contains extensive references.) (Author/CR)