Biomedical subjects

J C DeFries

Publications and source records attributed to J C DeFries.

At least 37 records · Page 2Linked to original sources

PubMed1997

Comorbidity of mathematics and reading deficits: evidence for a genetic etiology.

In order to assess the genetic etiology of the comorbidity of reading and mathematics difficulties, data were ascertained from two samples: (1) 102 identical and 77 same-sex fraternal twin pairs in which at least one member of each pair is reading disabled and (2) 42 identical and 23 same-sex fraternal twin pairs in which at least one member is math disabled. Composite reading and mathematics performance data from each sample were fitted to the basic multiple regression model for the analysis of selected twin data and its bivariate extension. Resulting estimates of bivariate heritability and the genetic correlation between the reading and the mathematics performance measures suggest that the comorbidity between mathematics and reading difficulties is due in part to genetic influences.

Adolescent↗

PubMed1997

Behavioral genetics '97: ASHG statement. Recent developments in human behavioral genetics: past accomplishments and future directions.

The field of behavioral genetics has enormous potential to uncover both genetic and environmental influences on normal and deviant behavior. Behavioral-genetic methods are based on a solid foundation of theories and methods that successfully have delineated components of complex traits in plants and animals. New resources are now available to dissect the genetic component of these complex traits. As specific genes are identified, we can begin to explore how these interact with environmental factors in development. How we interpret such findings, how we ask new questions, how we celebrate the knowledge, and how we use or misuse this knowledge are all important considerations. These issues are pervasive in all areas of human research, and they are especially salient in human behavioral genetics.

Adoption↗

PubMed1996

Quantitative trait loci for ethanol sensitivity in the LS x SS recombinant inbred strains: interval mapping.

We are mapping the genes (quantitative trait loci or QTLs) that are responsible for individual differences in ethanol sensitivity, measured as the duration of loss of righting, reflex (LORR) and blood ethanol concentrations upon recovery of the righting reflex (BEC). The Long-Sleep (LS) and Short-Sleep (SS) selected lines of mice manifest an 18-fold difference in LORR and serve as a rodent model for ethanol sensitivity. The LS x SS recombinant inbred (RI) series, developed from LS and SS lines, are an important resource for QTL mapping of ethanol-related responses. The current report summarizes the initial QTL analysis of LORR and BEC in the LS x SS strains and compares the results of correlational analysis with an interval-mapping approach. The data provide strong evidence for QTLs that influence ethanol sensitivity on mouse chromosomes 1 and 2 and possible QTLs on chromosomes 1, 3, 4, 5, 6, 7, 12, 13, 16, and 18. These results are compared to those from an F2 cross which confirms QTLs on chromosomes 1, 2, 4, and 18.

Alcohol Drinking↗

PubMed1996

Genetic and environmental influences on temperament in middle childhood: analyses of teacher and tester ratings.

Parent ratings of temperament in infancy and childhood yield evidence for genetic influence in twin studies but not in adoption studies. The present study used the sibling adoption design to investigate teacher and tester ratings of temperament in middle childhood. When each child was 7 years old, ratings on the Colorado Childhood Temperament Inventory were obtained from a teacher and tester for more than 50 pairs each of adoptive and nonadoptive siblings in the Colorado Adoption Project. Significant genetic influence emerged for both teacher and tester ratings of Activity, for tester ratings of Sociability, and for teacher ratings of Emotionality. Results obtained from bivariate genetic analysis suggest that the modest covariance between teacher and tester ratings of Activity is entirely mediated genetically. Except for teacher ratings of Attention Span, evidence of shared family environment was nonsignificant, despite the power of the sibling adoption design to detect it.

Adoption↗

PubMed1995

A simple genetic basis for a complex psychological trait in laboratory mice.

Psychological traits are commonly inferred from covariation in sets of behavioral measures that otherwise appear to have little in common. Emotionality in mice is such a trait, defined here by covariation in activity and defecation in a novel environment and emergence into the open arms of an elevated plus maze. Behavioral and quantitative trait analyses were conducted on four measures obtained from 879 mice from an F2 intercross. Three loci, on murine chromosomes 1, 12, and 15, were mapped that influence emotionality. This trait, inferred from studies of strain, sex, and individual differences in rodents, may be related to human susceptibility to anxiety or neuroticism.

Animals↗

PubMed1995

Quantitative trait locus for reading disability: correction.

In the news article "Can risky mergers save hospital-based research?" by Wade Roush (19 May, p. 968), the statement that University Hospitals of Cleveland rose from 20th in the rankings of teaching hospitals funded by the National Institutes of Health (NIH) in 1991 to 12th at present was incorrect. In fact, it was Case Western Reserve University (CWRU), with which University Hospitals of Cleveland is affiliated, that received $69 million in NIH grants in 1993, making it the 20th largest recipient of such grants among medical centers; the university then received $97 million in 1994, raising its rank to 12th. About $15 million of the increase, or 53%, was attributable to CWRU's 1992 affiliation with Henry Ford Hospital in Detroit. Other hospitals affiliated with Case Western include MetroHealth Medical Center, Mount Sinai Medical Center, St. Luke's Medical Center, and Cleveland Veterans' Affairs Medical Center.

Chromosome Mapping↗

PubMed1995

Cognitive ability and academic achievement in the Colorado Adoption Project: a multivariate genetic analysis of parent-offspring and sibling data.

To test the hypothesis that the etiology of covariation among measures of cognitive ability and academic achievement is due at least in part to shared genetic influences, data from 198 adoptive and 220 nonadoptive families participating in the Colorado Adoption Project were subjected to multivariate behavioral genetic analyses. Data on measures of cognitive ability (verbal comprehension and perceptual organization) and academic achievement (reading recognition and mathematics achievement) from related and unrelated sibling pairs tested at age 7, as well as from adoptive and nonadoptive parents, were analyzed. Phenotypic analyses confirmed previous findings of moderate correlations among measures of cognitive ability and achievement, averaging about .35. Although 54% of the covariation between reading and mathematics achievement was due to influences shared with verbal ability, a significant proportion of this covariation was independent of the cognitive ability measures. Heritabilities for the various measures were moderate, ranging from .21 to .37. Moreover, genetic influences accounted for 33-64% of their phenotypic covariation; for example, 33-60% of the observed correlations between verbal comprehension and the achievement measures, 64% of those between perceptual organization and the achievement measures, and 63% of that between reading recognition and mathematics achievement were due to shared genetic influences. Similar to the results of the phenotypic analysis, nearly half of the genetic covariance between reading and mathematics achievement was independent of cognitive ability. Their remaining covariance was due primarily to nonshared environmental influences.

Adoption↗

PubMed1995

Etiology of individual differences in reading performance: a test of sex limitation.

To test the hypothesis that the etiology of individual differences in reading performance differs in males and females, reading performance data from twin pairs tested in the Colorado Learning Disabilities Research Center were fitted to structural equation models of sex limitation. The sample included 513 pairs of twins in which at least one member of each pair has a positive school history of reading problems [228 monozygotic (MZ), 176 same-sex dizygotic (DZ), and 109 opposite-sex DZ pairs] and 302 matched control pairs [148 MZ, 98 same-sex DZ, and 56 opposite-sex DZ pairs]. Estimates of the genetic correlation between performance in males and females were obtained by analysis of data from both same-sex and opposite-sex twin pairs (Neale and Cardon, 1992). The full model fit the data well (chi 2 = 17.74, df = 16, p = 0.340), and the resulting genetic parameter estimates were highly similar in males and females in both the proband and the control samples. The correlations between genetic influences in males and females do not differ among groups (change in chi 2 = 0.95, df = 1, p > or = 0.25), and the resulting pooled estimate is about .5. Thus, results of this analysis suggest that the etiology of individual differences in reading performance may differ to some extent in males and females.

Adolescent↗

PubMed1995

Multivariate genetic analysis of Wechsler Intelligence Scale for Children--Revised (WISC-R) factors.

Wechsler Intelligence Scale for Children--Revised (WISC-R) factor scores (Verbal Comprehension, Perceptual Organization, and Freedom from Distractibility) were obtained from 574 twin pairs in the Colorado Reading Project and subjected to multivariate genetic analysis. Variances were partitioned into components common to the three WISC-R factors and to those specific to each factor. Substantial commonality, both genetic and environmental, was found among the three factors. The full model fit the data well, and estimates of heritability and environmentality indicated that about half of the phenotypic variance for each factor is due to additive genetic effects. These results were compared to those obtained in a previous twin study of the three Wechsler Adult Intelligence Scale (WAIS) factors by Tambs et al. (1986).

Adolescent↗

PubMed1995

Ethanol-induced anesthesia in inbred strains of long-sleep and short-sleep mice: a genetic analysis of repeated measures using censored data.

We present a repeated-measures, genetic analysis of ethanol-induced anesthesia (sleep time) in mice from the inbred long-sleep (ILS) and short-sleep (ISS) strains of mice and their derived F1 and F2 generations. Mice (total N > 1300) were administered a 4.1 g/kg intraperitoneal dose of ethanol at two times, 7 to 10 days apart. A method suggested by Cohen was used to analyze the resulting data, which contained a known number of unmeasured observations. A genetic model that included both additive and epistatic parameters fitted the adjusted data well. A novel procedure for estimating heritability, based on a comparison of repeatability coefficients from the isogenic and genetically segregating populations, was also employed. Results of this analysis suggested that the heritability for individual measurements of sleep time is about .30, whereas the heritability of average scores is about .40. Results of this analysis also confirm that the ILS and ISS strains differ for genes at seven or more loci that influence sleep time. Since the ILS and ISS were derived by inbreeding the LS and SS lines, these results further suggest that almost all of the genetic variation present in the selected lines have been maintained in the ILS and ISS strains.

Animals↗

PubMed1995

Use of repeated measures in an analysis of ethanol-induced loss of righting reflex in inbred long-sleep and short-sleep mice.

We present a repeated-measures analysis of ethanol-induced loss of righting reflex (LRR) in Inbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS) strains of mice and their F1 and F2 cross progeny. Mice were administered a 4.1 g/kg intraperitoneal dose of ethanol at two times, 7-10 days apart. Repeatability is nonsignificant in ILS, ISS, and F1 mice, but is highly significant (0.47, p < 0.01) in the F2 mice. Mean LRR does not differ between trials 1 and 2, with the exception of the ISS strain in which the interaction of sex with LRR sensitization is significant. This two-trial method leads to increased accuracy of genotype assessment for pharmacological or behavioral traits where trial 1 does not influence the outcome of trial 2. The repeated-measures design facilitates novel analyses of the duration of LRR, and results suggest that most environmental variance for LRR is due to nonreplicable influences.

Alcoholic Intoxication↗

PubMed1995

Comorbidity of reading and mathematics disabilities: genetic and environmental etiologies.

Although children with learning disabilities frequently manifest comorbid reading and mathematics deficits, the cause of this comorbidity is unknown. To assess the extent to which comorbidity between reading and mathematics deficits is due to genetic and environmental influences, we conducted a twin study of reading and mathematics performance. Data from 148 identical and 111 fraternal twin pairs in which at least one member of the pair had a reading disability were subjected to a cross-concordance analysis and also fitted to a bivariate extension of the basic multiple regression model for the analysis of selected twin data. Results of these analyses suggest that genetic and shared-environmental influences both contribute to the observed covariance between reading and mathematics deficits.

Adolescent↗

PubMed1994

Quantitative trait locus for reading disability on chromosome 6.

Interval mapping of data from two independent samples of sib pairs, at least one member of whom was reading disabled, revealed evidence for a quantitative trait locus (QTL) on chromosome 6. Results obtained from analyses of reading performance from 114 sib pairs genotyped for DNA markers localized the QTL to 6p21.3. Analyses of corresponding data from an independent sample of 50 dizygotic twin pairs provided evidence for linkage to the same region. In combination, the replicate samples yielded a chi 2 value of 16.73 (P = 0.0002). Examination of twin and kindred siblings with more extreme deficits in reading performance yielded even stronger evidence for a QTL (chi 2 = 27.35, P < 0.00001). The position of the QTL was narrowly defined with a 100:1 confidence interval to a 2-centimorgan region within the human leukocyte antigen complex.

Adolescent↗

PubMed1994

Commingling and segregation analysis of reading performance in families of normal reading probands.

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.

Child↗

PubMed1994

Continuity and change in infant shyness from 14 to 20 months.

Objective measures of shyness in the MacArthur Longitudinal Twin Study were obtained in two testing situations: the laboratory and the home. A longitudinal hierarchical model was fitted to the data, allowing estimation of the extent to which genetic, shared environmental, and unique environmental influences contributed to continuity and change of the shyness phenotype from 14 to 20 months of age. The sample consisted of 163 monozygotic and 138 same-sex dizygotic twin pairs. Models were fitted to raw data using a maximum-likelihood pedigree approach. Genetic, shared environmental, and unique environmental first-order factors, with specific variances, were modeled on each of four shyness ratings assessed in the laboratory and home at 14 and 20 months. Four second-order genetic, shared environmental, and unique environmental factors were also modeled. Results indicated that developmental change from 14 to 20 months and situational specificity between the laboratory and the home are mediated largely by shared and unique environmental influences. Genetic variation is largely responsible for both the stability in shyness from 14 to 20 months and the phenotypic correlations observed between the laboratory and the home settings.

Female↗

PubMed1994

Individual differences in sensitivity to nicotine in mice: response to six generations of selective breeding.

Four hundred seventeen heterogeneous stock mice were tested for their relative sensitivity to a low dose of nicotine (0.75 mg/kg) using activity in an automated Y-maze and body temperature as response measures. A wide spectrum of individual responsiveness to nicotine, ranging from complete suppression of activity to stimulation above baseline activity, was found. Replicate measures taken 1 week later on the same animals showed the responses to nicotine to be reliable and reproducible. Activity levels and body temperatures following nicotine administration were highly correlated (r = 0.60, df = 415). From analysis of between-litter proportions of variance, the heritability of nicotine-influenced activity was estimated to be 0.12, indicating that selective breeding for differential responsiveness to nicotine would be possible. The 10 most activated and 10 most depressed male and female mice were chosen as breeders for replicate nicotine activated (NA) and nicotine depressed (ND) lines, respectively. The selection criterion was nicotine-induced activity corrected for baseline activity using regression residuals. After six generations of selective breeding a good response to selection was obtained, although the response was better for the ND than for the NA lines. Realized heritability for responsiveness to nicotine calculated from the six selected generations was found to be 0.20, or slightly greater than that estimated from the foundation population. There were no significant differences in response to selection between the replicate NA or ND lines. Nicotine-induced body temperature was measured as a correlated response to selection, and was found to remain highly correlated with nicotine-induced locomotor activity. The response was more robust for the ND lines than it was for the NA lines. In contrast to the large differences between the ND and NA lines in locomotor activity and body temperatures following nicotine administration, mean baseline activities and body temperatures remained nearly identical throughout. This indicates that selection acted specifically on nicotine-induced responses, and not on baseline measurements, as predicted for response to a selection criterion based on regression residuals.

Animals↗

PubMed1993

Hyperactivity and spelling disability: testing for shared genetic aetiology.

The influence of genetic factors in the comorbidity of spelling disability and hyperactivity was investigated in two samples of 190 and 260 same sex twin pairs. The method of bivariate group heritability was used to estimate the genetic correlation for spelling disability and hyperactivity. A similar though not statistically significant value for the genetic correlation was obtained for the two samples (0.29 and 0.42). It was estimated that approximately 75% of the co-occurrence of these two conditions was due to shared genetic influences.

Adult↗

PubMed1993

Cognitive abilities of children at 7 and 12 years of age in the Colorado adoption project.

To test the hypothesis that adopted children are at an elevated risk for learning disabilities, the achievement and WISC-R test scores of a nonclinical sample of adopted and nonadopted (control) children were compared at 7 years of age (n = 108 adopted males, 91 adopted females, 116 control males, 100 control females) and 12 years of age (n = 69 adopted males, 61 adopted females, 56 control males, 44 control females). Although the average Verbal IQ of the adopted children was significantly lower than that of the nonadopted children at both ages, these differences accounted for only about 2% to 4% of the variance. When scores on the individual subtests of the WISC-R were compared, the group difference was significant only for Similarities at age 7, and for Comprehension at age 12. Moreover, with regard to the achievement tests, the proportion of adopted children who scored more than 1.5 standard deviations below expected, based on IQ, was not significantly greater than that of controls. Also, the proportions of adopted and control children placed in special education classes were not significantly different. Thus, the results of this study provide little or no evidence for an increased risk of learning disabilities in "easily placed" adopted children.

Achievement↗