Colorado Twin Research Articles

Assessing an Extended Version of the Not-So-Simple View of Writing Model in School-Aged Students With Attention-Deficit/Hyperactivity Disorder

Students with Attention-Deficit/Hyperactivity Disorder (ADHD) are struggling writers. Yet no comprehensive model has been validated to explain their poor writing outcomes. This study aims to test whether an extended version of the Not-So-Simple View of Writing (NSVW) model can describe the effects of key abilities on writing performance in students with ADHD. The sample included students with and without ADHD who completed cognitive and academic measures in the Colorado Twin Project. A Multi-Group Structural Equation Model approach revealed that multiple broad cognitive abilities predicted student writing performance and basic writing skills predicted more advanced writing skills. Model fit was excellent both for a model with writing as a single latent variable (fully latent) and as interrelated manifest variables (partially latent). Furthermore, students with and without ADHD demonstrated comparable patterns of relationships among the variables in the model. Implications for the assessment of writing difficulties in students with ADHD are discussed.

The Colorado Twin Registry: 2019 Update.

The Colorado Twin Registry (CTR) is a population-based registry formed from birth and school records including twins born between 1968 and the present. Two previous reports on the CTR [Rhea et al., (2006). Twin Research and Human Genetics, 9, 941-949; Rhea et al., (2013).Twin Research and Human Genetics, 16, 351-357] covered developments in the CTR through 2012. This report briefly summarizes previously presented material on ascertainment and recruitment and the relationships between samples and studies, discusses developments since 2012 for four previously described twin samples, describes two new samples and their complementary studies and expands on two subjects briefly mentioned in the last report: a history of genotyping efforts involving CTR samples, and a survey of collaborations and consortia in which CTR twins have been included. The CTR remains an active resource for both ongoing, longitudinal research and the recruitment of new twin samples for newly identified research opportunities.

Genetic influences on the human oral microbiome

BackgroundThe human oral microbiome is formed early in development. Its composition is influenced by environmental factors including diet, substance use, oral health, and overall health and disease. The influence of human genes on the composition and stability of the oral microbiome is still poorly understood. We studied both environmental and genetic characteristics on the oral microbiome in a large twin sample as well as in a large cohort of unrelated individuals. We identify several significantly heritable features of the oral microbiome. The heritability persists in twins even when their cohabitation changes. The heritability of these traits correlates with the cumulative genetic contributions of over half a million single nucleotide sequence variants measured in a different population of unrelated individuals. Comparison of same-sex and opposite sex cotwins showed no significant differences. We show that two new loci on chromosomes 7 and 12 are associated with the most heritable traits.ResultsAn analysis of 752 twin pairs from the Colorado Twin Registry, shows that the beta-diversity of monozygotic twins is significantly lower than for dizygotic or unrelated individuals. This is independent of cohabitation status. Intraclass correlation coefficients of nearly all taxa examined were higher for MZ than DZ twin pairs. A comparison of individuals sampled over 2-7 years confirmed previous reports that the oral microbiome remains relatively more stable in individuals over that time than to unrelated people. Twin modeling shows that a number of microbiome phenotypes were more than 50% heritable consistent with the hypothesis that human genes influence microbial populations. To identify loci that could influence microbiome phenotypes, we carried out an unbiased GWAS analysis which identified one locus on chromosome 7 near the gene IMMPL2 that reached genome-wide significance after correcting for multiple testing. Another locus on chromosome 12 near the non-coding RNA gene INHBA-AS1 achieved genome-wide significance when analyzed using KGG4 that sums SNP significance across coding genes.DiscussionUsing multiple methods, we have demonstrated that some aspects of the human oral microbiome are heritable and that with a relatively small sample we were able to identify two previously unidentified loci that may be involved.

Higher Rates of DZ Twinning in a Twenty-First Century Birth Cohort.

The Colorado Twin Registry is a population based registry initiated in 1984 with the involvement of the Colorado Department of Health, Division of Vital Statistics. Recruitment includes birth cohorts several years prior to 1984 and all subsequent years. As part of a recent evaluation of Colorado birth records for the years 2006 through 2008 we became aware of a shifting trend in the proportion of MZ and DZ twins in the Colorado population. Historically (Bulmer 1970 The biology of twinning in man, Clarendon, Oxford) we have expected a 1/3, 1/3, 1/3 ratio of MZ, same-sex DZ and opposite sex DZ twins in Caucasian populations. An excess of MZ pairs in most studies was assumed to be due to selection bias. Somewhat more recently, Hur et al.(1995 Behav Genet 25, 337-340) provided evidence that the DZ twinning rate was falling and that therefore selection bias was not the reason for higher MZ enrollment in most twin studies. They suggested that twin researchers might consider strategies to over-enroll DZ pairs to maximize statistical power. In contrast, we now find that of the 3217 twin births in Colorado from 2006 to 2008 with identified sex information the MZ rate is estimated at only 22%, and we have corroborating reports from other states of similar estimates. These were calculated applying Weinberg's rule which assumes an equal birth rate for same sex and opposite sex DZ pairs so that the proportion of MZ in a sample is the proportion of same sex (MM + FF) minus the proportion of opposite-sex (MF, FM). We explore factors, such as an increase in the proportion of non-Caucasian parents and an increase in average maternal age, which may contribute to this shift.

Association between 5HTT, DAT1, and DRD4 and bipolar disorder in youth

Cosgrove, Victoria E.a,c,d; Miklowitz, David J.b,c; Rhee, Soo Hyunc,d; Hawkey, Christopherc; Corley, Robind; Haberstick, Brettd; Smolen, Andrewd Author Information

Colorado Twin Registry: an update.

The Colorado Twin Registry (CTR) is a population-based registry housed at the Institute for Behavioral Genetics at the University of Colorado. Recruitment began in 1982 and includes twins born from 1968 to the present. Four samples are currently drawn from the CTR: The Community Twin Sample, the Longitudinal Twin Sample, the Early Reading Development Sample, and the Colorado Learning Sample. Criteria for enrollment, recruitment strategies, demographic information, and zygosity assignment are explained for each sample. In addition, five studies in which CTR twins are now participating are highlighted. These include studies of cognition, learning ability, and vulnerability to substance abuse and antisocial behavior. The development of the CTR is an ongoing and evolving process, and it has proven to be a valuable registry, relatively representative of the population from which it was drawn.

Developmental epidemiology of drug use and abuse in adolescence and young adulthood: Evidence of generalized risk

Past studies highlight a narrowing gender gap and the existence of a shared etiology across substances of abuse; however, few have tested developmental models using longitudinal data. We present data on developmental trends of alcohol, tobacco, and marijuana use, abuse and dependence assessed during adolescence and young adulthood in a community-based Colorado twin sample of 1733 respondents through self-report questionnaires and structured psychiatric interviews. Additionally, we report on the rates of multiple substance use and disorders at each developmental stage, and the likelihood of a substance use disorder (SUD; i.e., abuse or dependence) diagnosis in young adulthood based on adolescent drug involvement. Most notably, we evaluate whether the pattern of multiple substance use and disorders and likelihood ratios across substances support a model of generalized risk. Lastly, we evaluate whether the ranked magnitudes of substance-specific risk match the addiction liability ranking. Substance use and SUDs are developmental phenomena, which increase from adolescence to young adulthood with few and inconsistent gender differences. Adolescents and young adults are not specialized users, but rather tend to use or abuse multiple substances increasingly with age. Risk analyses indicated that progression toward a SUD for any substance was increased with prior involvement with any of the three substances during adolescence. Despite the high prevalence of alcohol use, tobacco posed the greatest substance-specific risk for developing subsequent problems. Our data also confirm either a generalized risk or correlated risk factors for early onset substance use and subsequent development of SUDs.

Common genetic and environmental influences on major depressive disorder and conduct disorder.

The evidence for common genetic and environmental influences on conduct disorder (CD) and major depressive disorder (MDD) in adolescents was examined. A sample of 570 monozygotic twin pairs, 592 dizygotic twin pairs, and 426 non-twin siblings, aged 12-18 years, was recruited from the Colorado Twin Registry. For the past year data, there was a significant correlation between the genetic influences on MDD and CD and, for the lifetime data, there was a significant correlation between the genetic influences on MDD and CD, and a significant correlation between the nonshared environmental influences on MDD and CD. Our results suggest that some genetic factors will increase an individual's vulnerability to both MDD and CD in adolescence.

Colorado Twin Registry

AbstractThe Colorado Twin Registry (CTR) is a population-based registry housed at the Institute for Behavioral Genetics, University of Colorado. Recruited subjects' birth years date from 1968. Four samples comprise the CTR: the Community Twin Sample, Infant Twin Sample, Longitudinal Twin Sample, and the Early Reading Development Sample. Criteria for enrollment, recruitment strategies, demographic information and zygosity assignment are explained for each sample. In addition, 8 studies in which CTR twins have participated are highlighted. These include studies of early cognition, early reading ability, executive cognitive function, and vulnerability to substance abuse and antisocial behavior. Goals, measures, and brief results are provided for each study. The development of the CTR is an ongoing and evolving process, and it has proved to be a valuable resource, relatively representative of the population from which it was drawn.

Colorado Twin Registry

The Colorado Twin Registry (CTR) is a population-based registry housed at the Institute for Behavioral Genetics, University of Colorado. Recruited subjects' birth years date from 1968. Four samples comprise the CTR: the Community Twin Sample, Infant Twin Sample, Longitudinal Twin Sample, and the Early Reading Development Sample. Criteria for enrollment, recruitment strategies, demographic information and zygosity assignment are explained for each sample. In addition, 8 studies in which CTR twins have participated are highlighted. These include studies of early cognition, early reading ability, executive cognitive function, and vulnerability to substance abuse and antisocial behavior. Goals, measures, and brief results are provided for each study. The development of the CTR is an ongoing and evolving process, and it has proved to be a valuable resource, relatively representative of the population from which it was drawn.

Examination of the Causes of Covariation Between Conduct Disorder Symptoms and Vulnerability to Drug Dependence

Conduct disorder (CD) symptoms and substance dependence commonly co-occur. Both phenotypes are highly heritable and a common genetic influence on the covariation has been suggested. The aim of this study was to determine the extent to which genes and environment contribute to the covariance between CD and drug dependence using twins from the Colorado Longitudinal Twin Sample and the Colorado Twin Registry. A total of 880 twin pairs (237 monozygotic [MZ] female, 195 MZ male, 116 dizygotic [DZ] female, 118 DZ male and 214 DZ opposite-sex) aged 13 to 18 (mean = 15.65) were included in the analysis. CD was assessed by lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) symptom count and a polysubstance dependence vulnerability index was developed from responses to the Composite International Diagnostic Interview--Substance Abuse Module. A bivariate Cholesky Decomposition model was used to partition the cause of variation and covariation of the two phenotypes. No sex-limitation was observed in our data, and male and female parameter estimates were constrained to be equal. Both CD symptoms and dependence vulnerability were significantly heritable, and genes, shared environment and nonshared environment all contributed to the covariation between them. Genes contributed 35% of the phenotypic covariance, shared environment contributed 46%, and nonshared environmental influences contributed the remaining 19% to the phenotypic covariance. Therefore, there appears to be pleiotropic genetic influence on CD symptoms and dependence vulnerability.

Examination of the Causes of Covariation Between Conduct Disorder Symptoms and Vulnerability to Drug Dependence

AbstractConduct disorder (CD) symptoms and substance dependence commonly co-occur. Both phenotypes are highly heritable and a common genetic influence on the covariation has been suggested. The aim of this study was to determine the extent to which genes and environment contribute to the covariance between CD and drug dependence using twins from the Colorado Longitudinal Twin Sample and the Colorado Twin Registry. A total of 880 twin pairs (237 monozygotic [MZ] female, 195 MZ male, 116 dizygotic [DZ] female, 118 DZ male and 214 DZ opposite-sex) aged 13 to 18 (mean = 15.65) were included in the analysis. CD was assessed by lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) symptom count and a polysubstance dependence vulnerability index was developed from responses to the Composite International Diagnostic Interview — Substance Abuse Module. A bivariate Cholesky Decomposition model was used to partition the cause of variation and covariation of the two phenotypes. No sex-limitation was observed in our data, and male and female parameter estimates were constrained to be equal. Both CD symptoms and dependence vulnerability were significantly heritable, and genes, shared environment and nonshared environment all contributed to the covariation between them. Genes contributed 35% of the phenotypic covariance, shared environment contributed 46%, and nonshared environmental influences contributed the remaining 19% to the phenotypic covariance. Therefore, there appears to be pleiotropic genetic influence on CD symptoms and dependence vulnerability.

Genetic influences on reading difficulties in boys and girls: the Colorado twin study

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> or = 0.17). The estimate of group heritability (h2g), 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 > or = 0.35). Gender differences in h2g 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 > or = 0.86) or continuously (p > or = 0.71). Thus, results of this study provide little or no evidence for a differential genetic etiology of reading difficulties in males and females.

TDT-association analysis of EKN1 and dyslexia in a Colorado twin cohort

A candidate gene, EKN1, was recently described in a cohort from Finland for the dyslexia locus on chromosome 15q, DYX1. This report described a (2;15) (q11;21) translocation disrupting EKN1 that cosegregated with dyslexia in a two-generation family. It also characterized a sequence polymorphism in the 5' untranslated region and a missense mutation that showed significant association in 109 dyslexics compared to 195 controls (p=0.002 and p=0.006, respectively). To confirm these results we interrogated the same polymorphisms in a cohort of 150 nuclear families with dyslexia ascertained through the Colorado Learning Disabilities Research Center. Using QTDT analysis with nine individual quantitative tasks and two composite measures of reading performance, we could not replicate the reported association. We conclude that the polymorphisms identified in the Finland sample are unlikely to be functional DNA changes contributing to dyslexia, and that if variation in EKN1 is causal such changes are more likely to be in regulatory regions that were not sequenced in this study. Alternatively, the published findings of association with markers in EKN1 may reflect linkage disequilibrium with variation in another gene(s) in the region.

A 77-Kilobase Region of Chromosome 6p22.2 Is Associated with Dyslexia in Families From the United Kingdom and From the United States

Several quantitative trait loci (QTLs) that influence developmental dyslexia (reading disability [RD]) have been mapped to chromosome regions by linkage analysis. The most consistently replicated area of linkage is on chromosome 6p23-21.3. We used association analysis in 223 siblings from the United Kingdom to identify an underlying QTL on 6p22.2. Our association study implicates a 77-kb region spanning the gene TTRAP and the first four exons of the neighboring uncharacterized gene KIAA0319. The region of association is also directly upstream of a third gene, THEM2. We found evidence of these associations in a second sample of siblings from the United Kingdom, as well as in an independent sample of twin-based sibships from Colorado. One main RD risk haplotype that has a frequency of approximately 12% was found in both the U.K. and U.S. samples. The haplotype is not distinguished by any protein-coding polymorphisms, and, therefore, the functional variation may relate to gene expression. The QTL influences a broad range of reading-related cognitive abilities but has no significant impact on general cognitive performance in these samples. In addition, the QTL effect may be largely limited to the severe range of reading disability.

Etiology of reading difficulties and rapid naming: the Colorado Twin Study of Reading Disability.

Children with reading deficits perform more slowly than normally-achieving readers on speed of processing measures, such as rapid naming (RN). Although rapid naming is a well-established correlate of reading performance and both are heritable, few studies have attempted to assess the cause of their covariation. Measures of rapid naming (numbers, colors, objects, and letters subtests), phonological decoding, orthographic choice, and a composite variable (DISCR) derived from the reading recognition, reading comprehension, and spelling subtests of the Peabody Individual Achievement Test were obtained from a total of 550 twin pairs with a positive school history of reading problems. Basic DeFries and Fulker (DF) multiple regression models for the analysis of selected twin data confirmed the heritable nature of phonological decoding, orthographic choice, DISCR, and rapid-naming composites. Bivariate DF models were employed to examine the extent to which deficits in the three reading-related measures covary genetically with rapid naming. Significant bivariate heritability estimates for each of the reading measures with the numbers and letters rapid-naming composite were also obtained. As expected, univariate sib-pair linkage analyses indicated the presence of a quantitative trait locus (QTL) on chromosome 6p21.3 for phonological decoding and orthographic choice deficits. Bivariate linkage analyses were then conducted to test the hypothesis that this QTL for reading difficulties is pleiotropic for slower performance on RN tasks. The results obtained from these analyses did not provide substantial evidence that the 6p QTL for reading difficulties has significant effects on rapid naming; however, larger samples would be required to test this hypothesis more rigorously.

NEW AND RARE CHRYSOPHYTES FROM WYOMING AND COLORADO LAKES

Colorado and Wyoming lakes with high pH values generally ranging from 8 to 10 are dominated by phytoplankton belonging to the chrysophytes, diatoms and cryptomonads. Our studies on phytoplankton diversity in Dowdy, South Delaney Buttes and Cowdrey Lakes in Colorado and Diamond and Twin Buttes Lakes in Wyoming have yielded several isolates of rare or new chrysophytes. These isolates were examined with light microscopy, SEM, TEM, and novel information regarding their structure is presented. Proposed new species belong to the genera Saccochrysis, Prymnesium and Chrysochromulina. Chrysophytes that were examined for the first time include Monochrysis aphanaster, Uroglenopsis, and a mixotrophic species of Ochromonas, which ingests small diatoms. Probable new species are the following: Saccochrysis sp. nov. differs in chloroplast structure, cell shape and cell number/colony, and absence of a posterior vacuole; Prymnesium sp. nov. is the first freshwater form examined with EM and differs in scale morphology; and Chrysochromulina sp. nov. is similar to Chrysochromulina parva but lacks scales. The ultrastructure of M. aphanaster is unique and appears to be a member of the Chrysophyceae. It has two flagella, one of which is emergent, while the other is hidden within an invagination of the cytoplasm. Diacronema and Sarcinochrysis spp. from these lakes also were isolated and reinvestigated, and some unique cellular features will be discussed.

Genetic and environmental influences on behavioral disinhibition

Comorbidity among childhood disruptive behavioral disorders is commonly reported in both epidemiologic and clinical studies. These problems are also associated with early substance use and other markers of behavioral disinhibition. Previous twin research has suggested that much of the covariation between antisocial behavior and alcohol dependence is due to common genetic influences. Similar results have been reported for conduct problems and hyperactivity. For the present study, an adolescent sample consisting of 172 MZ and 162 DZ twin pairs, recruited through the Colorado Twin Registry and the Colorado Longitudinal Twin Study were assessed using standardized psychiatric interviews and personality assessments. DSM-IV symptom counts for conduct disorder and attention deficit hyperactivity disorder, along with a measure of substance experimentation and novelty seeking, were used as indices of a latent behavioral disinhibition trait. A confirmatory factor model fit to individual-level data showed a strong common factor accounting for 16-42% of the observed variance in each measure. A common pathway model evaluating the genetic and environmental architecture of the latent phenotype suggested that behavioral disinhibition is highly heritable (a(2) = 0.84), and is not influenced significantly by shared environmental factors. A residual correlation between conduct disorder and substance experimentation was explained by shared environmental effects, and a residual correlation between attention deficit hyperactivity disorder and novelty seeking was accounted for by genetic dominance. These results suggest that a variety of adolescent problem behaviors may share a common underlying genetic risk.

Genetics of specific reading disability

Results obtained from the Colorado Twin Study of Reading Disability provide compelling evidence for a genetic etiology. For the present report, multiple regression analyses were performed on reading performance data from 186 pairs of identical twins and 138 pairs of same-sex fraternal twins among whom at least one member of each pair has a reading disability. The results indicate that on average, more than half of the reading performance deficit of probands is a consequence of heritable influences. Moreover, individual differences within the affected twin sample are highly heritable, whereas shared environmental influences do not contribute importantly to twin resemblance. The results of these analyses also suggest that the etiology of reading disability may differ from that of individual differences in reading performance. Because the estimate of heritability for reading performance in affected twin pairs is substantially higher than that in a control sample, reading disability may be caused by one or more genes having major effects. These results are highly consistent with our recent report of a putative quantitative trait locus for reading disability in a small region on the short arm of chromosome 6. © 1996 Wiley-Liss, Inc.

Differences in reading strategies reflect differences in linguistic abilities1

A strong tendency towards a letter‐level recoding strategy in reading has traditionally been interpreted as a sign of poor skills in the visual modality. Dyslexics who read relatively few words ‘immediately’have been considered to suffer from poor visual discrimination and memory (e.g. Boder & Jarrico 1982). However, this assumption has never been experimentally verified. The present study compared reading skills and strategies with auditory skills and naming speed using 26 severely dyslexic adolescents and 26 younger, normal readers matched for reading level and IQ. Phonological discrimination abilities were found to account for much of the variance in phonological abilities in reading such as the ability to read nonsense words. Naming speed was found to explain much of the variance in reading strategies. The last result was replicated in a post hoc analysis of the data from the Colorado twin study (Olson et al. 1989). The result indicates that terms like ‘visually’impaired or ‘dyseidetic’used for poor whole‐word readers may be grossly misleading. Rather, dyslexics with a relatively small vocabulary of ‘sight words’may have specific difficulties with retrieval of the sounds of words, and teaching should develop methods to deal with this problem.