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J C DeFries

Publications and source records attributed to J C DeFries.

At least 19 recordsLinked to original sources
PubMed2006

Genetic and environmental influences on age at sexual initiation in the Colorado Adoption Project.

Whereas the majority of research on adolescent sexual initiation has focused solely on environmental factors, the present study used behavioral genetic analyses to investigate the relative contributions of genetic and environmental influences. Structural equation models were fitted to data from adoptive and non-adoptive sibling pairs (231 biologically related pairs and 169 unrelated pairs) from the Colorado Adoption Project. Information from censored individuals who had not yet experienced sexual initiation was maximized by adapting the twin survival analysis method of Pickles et al. (Behav Genet 24(5):457-468, 1994) to accommodate adoptive and non-adoptive siblings. Point estimates of variance components from an ACE model, including additive genetic (A), shared environmental (C), and non-shared environmental (E) influences were 28%, 24%, and 48%, respectively. Despite the lower point estimate for shared environmental effects than additive genetic effects, a CE model provided the best fit to the data. However, because adoptive siblings provide a direct estimate of shared environmental influences there is greater power to detect shared environmental effects in adoption designs. Evidence for genetic influences from our data were somewhat lower than those obtained in previous twin studies, possibly reflecting a return to more socially conservative sexual attitudes, changing sexual behaviors, or ambiguities in the wording of questions commonly used in research on adolescent sexuality.

Adolescent↗
PubMed2005

Bivariate linkage scan for reading disability and attention-deficit/hyperactivity disorder localizes pleiotropic loci.

BACKGROUND: There is a growing interest in the study of the genetic origins of comorbidity, a direct consequence of the recent findings of genetic loci that are seemingly linked to more than one disorder. There are several potential causes for these shared regions of linkage, but one possibility is that these loci may harbor genes with manifold effects. The established genetic correlation between reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD) suggests that their comorbidity is due at least in part to genes that have an impact on several phenotypes, a phenomenon known as pleiotropy. METHODS: We employ a bivariate linkage test for selected samples that could help identify these pleiotropic loci. This linkage method was employed to carry out the first bivariate genome-wide analysis for RD and ADHD, in a selected sample of 182 sibling pairs. RESULTS: We found evidence for a novel locus at chromosome 14q32 (multipoint LOD=2.5; singlepoint LOD=3.9) with a pleiotropic effect on RD and ADHD. Another locus at 13q32, which had been implicated in previous univariate scans of RD and ADHD, seems to have a pleiotropic effect on both disorders. 20q11 is also suggested as a pleiotropic locus. Other loci previously implicated in RD or ADHD did not exhibit bivariate linkage. CONCLUSIONS: Some loci are suggested as having pleiotropic effects on RD and ADHD, while others might have unique effects. These results highlight the utility of this bivariate linkage method to study pleiotropy.

Adolescent↗
PubMed2002

Evidence for linkage and association with reading disability on 6p21.3-22.

Reading disability (RD), or dyslexia, is a common heterogeneous syndrome with a large genetic component. Several studies have consistently found evidence for a quantitative-trait locus (QTL) within the 17 Mb (14.9 cM) that span D6S109 and D6S291 on chromosome 6p21.3-22. To characterize further linkage to the QTL, to define more accurately the location and the effect size, and to identify a peak of association, we performed Haseman-Elston and DeFries-Fulker linkage analyses, as well as transmission/disequilibrium, total-association, and variance-components analyses, on 11 quantitative reading and language phenotypes. One hundred four families with RD were genotyped with a new panel of 29 markers that spans 9 Mb of this region. Linkage results varied widely in degree of statistical significance for the different linkage tests, but multipoint analysis suggested a peak near D6S461. The average 6p QTL heritability for the 11 reading and language phenotypes was 0.27, with a maximum of 0.66 for orthographic choice. Consistent with the region of linkage described by these studies and others, there was a peak of transmission disequilibrium with a QTL centered at JA04 (chi2=9.48; empirical P=.0033; orthographic choice), and there was strong evidence for total association at this same marker (chi2=11.49; P=.0007; orthographic choice). Although the boundaries of the peak could not be precisely defined, the most likely location of the QTL is within a 4-Mb region surrounding JA04.

Adolescent↗
PubMed2002

Parent-offspring resemblance for reading performance at 7, 12 and 16 years of age in the Colorado Adoption Project.

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.

Adolescent↗
PubMed2001

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.

Adolescent↗
PubMed2001

Quantitative trait locus mapping in laboratory mice derived from a replicated selection experiment for open-field activity.

Bidirectional selection in rodents has been used to derive animal models of human behavior. An important question is whether selection for behavior operates on a limited number of QTL or whether the number and individual contribution of QTL varies between selection experiments. To address this question, we mapped QTL in two large F2 intercrosses (N = 815 and 821) from the four lines derived from a replicated selection experiment for open-field activity, an animal model for susceptibility to anxiety. Our analyses indicate that selection operated on the same relatively small number of loci in both crosses. Haplotype information and the direction of effect of each QTL allele were used to confirm that the QTL mapped in the two crosses lie in the same chromosomal regions, although we were unable to determine whether QTL in the two crosses represent the same genes. We conclude that the genetic architecture of the selected strains is similar and relatively simple.

Animals↗
PubMed2000

Twin study of the etiology of comorbidity between reading disability and attention-deficit/hyperactivity disorder.

This study utilized a sample of 313 eight- to sixteen-year-old same-sex twin pairs (183 monozygotic, 130 dizygotic) to assess the etiology of comorbidity between reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD). RD was assessed by a discriminant function score based on the Peabody Individual Achievement Test, a standardized measure of academic achievement. The DSM-III version of the Diagnostic Interview for Children and Adolescents was used to assess symptoms of ADHD, and separate factor scores were computed for inattention and hyperactivity/impulsivity (hyp/imp). Individuals with RD were significantly more likely than individuals without RD to exhibit elevations on both symptom dimensions, but the difference was larger for inattention than hyp/imp. Behavior genetic analyses indicated that the bivariate heritability of RD and inattention was significant (h(2)(g(RD/Inatt)) = 0.39), whereas the bivariate heritability of RD and hyp/imp was minimal and nonsignificant (h(2)(g(RD/Hyp)) = 0.05). Approximately 95% of the phenotypic covariance between RD and symptoms of inattention was attributable to common genetic influences, whereas only 21% of the phenotypic overlap between RD and hyp/imp was due to the same genetic factors.

Adolescent↗
PubMed2000

Etiology of inattention and hyperactivity/impulsivity in a community sample of twins with learning difficulties.

A community sample of 373 8 to 18 year-old twin pairs in which at least one twin in each pair exhibited a history of learning difficulties was utilized to examine the etiology of inattention and hyperactivity/impulsivity (hyp/imp). Symptoms of attention-deficit/hyperactivity disorder (ADHD) were assessed by the DSM-III Diagnostic Interview for Children and Adolescents. Inattention and hyp/imp composite scores were created based on results of a factor analysis. Results indicated that extreme ADHD scores were almost entirely attributable to genetic influences across several increasingly extreme diagnostic cutoff scores. Extreme inattention scores were also highly heritable whether or not the proband exhibited extreme hyp/imp. In contrast, the heritability of extreme hyp/imp increased as a linear function of the number of inattention symptoms exhibited by the proband. This finding suggests that extreme hyp/imp may be attributable to different etiological influences in individuals with and without extreme inattention. If this result can be replicated in other samples, it would provide evidence that the hyp/imp symptoms exhibited by individuals with Combined Type ADHD and Predominantly Hyp/Imp Type ADHD may be attributable to different etiological influences.

Achievement↗
PubMed2000

A twin MRI study of size variations in human brain.

Although it is well known that there is considerable variation among individuals in the size of the human brain, the etiology of less extreme individual differences in brain size is largely unknown. We present here data from the first large twin sample (N=132 individuals) in which the size of brain structures has been measured. As part of an ongoing project examining the brain correlates of reading disability (RD), whole brain morphometric analyses of structural magnetic response image (MRI) scans were performed on a sample of adolescent twins. Specifically, there were 25 monozygotic (MZ) and 23 dizygotic (DZ) pairs in which at least one member of each pair had RD and 9 MZ and 9 DZ pairs in which neither member had RD. We first factor-analyzed volume data for 13 individual brain structures, comprising all of the neocortex and most of the subcortex. This analysis yielded two factors ("cortical" and "subcortical") that accounted for 64% of the variance. We next tested whether genetic and environmental influences on brain size variations varied for these two factors or by hemisphere. We computed intraclass correlations within MZ and DZ pairs in each sample for the cortical and subcortical factor scores, for left and right neocortex, and for the total cerebral volume. All five MZ correlations were substantial (r's=.78 to.98) and significant in both samples, as well as being larger than the corresponding DZ correlations, (r's=0.32 to 0.65) in both samples. The MZ-DZ difference was significant for 3 variables in the RD sample and for one variable in the smaller control sample. These results indicate significant genetic influences on these variables. The magnitude of genetic influence did not vary markedly either for the 2 factors or the 2 hemispheres. There was also a positive correlation between brain size and full-scale IQ, consistent with the results of earlier studies. The total cerebral volume was moderately correlated (r=.42, p<.01, two-tailed) with full-scale IQ in the RD sample; there was a similar trend in the smaller control sample (r=.31, p<.07, two-tailed). Corrections of similar magnitude were found between the subcortical factor and full-scale IQ, whereas the results for the cortical factor (r=.16 and.13) were smaller and not significant. In sum, these results provide evidence for the heritability of individual differences in brain size which do not vary markedly by hemisphere or for neocortex relative to subcortex. Since there are also correlations between brain size and full-scale IQ in this sample, it is possible that genetic influences on brain size partly contribute to individual differences in IQ.

Adolescent↗
PubMed2000

Etiology of neuroanatomical correlates of reading disability.

The heritable nature of reading disability has been well documented (DeFries & Alarcón, 1996), and possible abnormalities of brain structures have been associated with the disorder (Filipek, 1995). However, the etiology of individual differences in morphological brain measures has not been examined extensively. The purpose of this study was to apply behavioral genetic methods to assess the etiology of individual differences in neuroanatomical structures. Measures of reading performance, cognitive ability, and magnetic resonance imaging scans were obtained from 25 monozygotic (MZ) and 23 same-sex dizygotic (DZ) twin pairs with reading disability, and 9 MZ and 9 DZ control twin pairs participating in the Colorado Learning Disabilities Research Center. Results obtained from multiple regression analyses (DeFries & Fulker, 1985, 1988) of these twin data indicated that individual differences in the size of most cortical and subcortical structures were largely due to heritable influences. Moreover, estimates of heritability did not change appreciably after controlling for IQ and total brain size.

Adolescent↗
PubMed2000

Self-reported reading problems in parents of twins with reading difficulties.

Parents of 323 twin pairs with reading disability (RD) reported significantly more problems learning to read (16% of mothers and 33% of fathers) than parents of 309 twin pairs without reading difficulties (6% of mothers and 9% of fathers). These rates of self-reported reading problems in parents of twins are highly similar to those previously obtained in parents of non-twin children with RD and controls, suggesting that the etiology of reading deficits in twin and non-twin children may also be highly similar. Moreover, within both the RD and control samples, twins whose parents self-reported a positive history of reading problems had lower reading performance test scores, on average, than those whose parents reported no reading problems. Therefore, results of the present twin study support those of previous studies with non-twin children in which parental self-reports have been found to provide a valid index of family history status for reading difficulties.

Achievement↗
PubMed2000

Are associations between parental divorce and children's adjustment genetically mediated? An adoption study.

The hypothesis that the association between parental divorce and children's adjustment is mediated by genetic factors was examined in the Colorado Adoption Project, a prospective longitudinal study of 398 adoptive and biological families. In biological families, children who experienced their parents' separation by the age of 12 years exhibited higher rates of behavioral problems and substance use, and lower levels of achievement and social adjustment, compared with children whose parents' marriages remained intact. Similarly, adopted children who experienced their (adoptive) parents' divorces exhibited elevated levels of behavioral problems and substance use compared with adoptees whose parents did not separate, but there were no differences on achievement and social competence. The findings for psychopathology are consistent with an environmentally mediated explanation for the association between parent divorce and children's adjustment; in contrast, the findings for achievement and social adjustment are consistent with a genetically mediated explanation involving passive genotype-environment correlation.

Adaptation, Psychological↗
PubMed1999

Brain morphometry in reading-disabled twins.

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.

Adolescent↗
PubMed1999

Quantitative-trait locus for specific language and reading deficits on chromosome 6p.

Reading disability (RD), or dyslexia, is a complex cognitive disorder manifested by difficulties in learning to read, in otherwise normal individuals. Individuals with RD manifest deficits in several reading and language skills. Previous research has suggested the existence of a quantitative-trait locus (QTL) for RD on the short arm of chromosome 6. In the present study, RD subjects' performance in several measures of word recognition and component skills of orthographic coding, phonological decoding, and phoneme awareness were individually subjected to QTL analysis, with a new sample of 126 sib pairs, by means of a multipoint mapping method and eight informative DNA markers on chromosome 6 (D6S461, D6S276, D6S105, D6S306, D6S258, D6S439, D6S291, and D6S1019). The results indicate significant linkage across a distance of at least 5 cM for deficits in orthographic (LOD = 3.10) and phonological (LOD = 2.42) skills, confirming previous findings.

Adult↗
PubMed1999

Etiology of covariation between reading and mathematics performance: a twin study.

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.

Achievement↗
PubMed1998

A twin and family study of the association between immune system dysfunction and dyslexia using blood serum immunoassay and survey data.

We conducted a study of the association between developmental reading disability (DRD) and immune disorders (ID) using both survey and immunoassay data in two separate samples of families. One sample was made up of twins and their parents and was ascertained through a population-based sampling scheme. The other sample was a set of extended pedigrees selected for apparent autosomal dominant transmission of DRD. We failed to find an association between DRD and ID in either sample, regardless of the method used to assess immune system function. Even though our twin sample provided evidence that both DRD and immune conditions were significantly heritable, there was no evidence for a genetic correlation between ID and DRD nor was there any clear indication that a special subgroup of individuals may be comorbid for these conditions because of genetic reasons. How these negative findings can be reconciled with the developmental hypothesis of Geschwind, Behan, Galaburda, and colleagues, and how they may relate to the gene locus influencing DRD that has been recently located in the HLA region of the short arm of chromosome 6 is discussed.

Adolescent↗
PubMed1998

Multivariate path analysis of specific cognitive abilities data at 12 years of age in the Colorado Adoption Project.

A parent-offspring multivariate conditional path model was fitted to specific cognitive abilities data from the Colorado Adoption Project (CAP) when the offspring were 12 years of age. The sample included 175 adoptees, 175 sets of adoptive parents, 175 biological mothers, 34 biological fathers, and 209 nonadopted children and their parents. Consistent with results obtained from multivariate genetic analyses of CAP data obtained at earlier ages, the effects of familial environmental transmission on individual differences in specific cognitive abilities were not significant. Assuming complete isomorphism (i.e., that the genetic and environmental etiologies of individual differences are the same) between the child and the adult measures, the heritability estimates for verbal, spatial, perceptual speed, and visual memory were .26, .35, .38, and .53, respectively. Although the heritability estimate for visual memory is somewhat higher than those for verbal, spatial, and perceptual speed abilities, these estimates are not significantly different. These estimates are higher than those obtained when the adoptees and controls were 4 years old (Rice et al., 1986, 1989); thus, heritabilities of specific cognitive abilities may increase as a function of cognitive development. Alternatively, genetic stability from childhood to adulthood may be greater from 12 years than from 4 years, which would be interpreted as greater heritability by the CAP parent-offspring design. The genetic correlations among the four measures were substantial, ranging from .27 between verbal and spatial abilities to .78 between spatial ability and perceptual speed. However, differences among these correlations are not significant, suggesting that their covariation may be due to general cognitive ability. Finally, estimates of bivariate-heritability indicate that on average about half of the phenotypic correlations among the four specific cognitive ability measures are due to genetic effects.

Adoption↗