The heritability of general cognitive ability increases linearly from childhood to young adulthood.

Although common sense suggests that environmental influences increasingly account for individual differences in behavior as experiences accumulate during the course of life, this hypothesis has not previously been tested, in part because of the large sample sizes needed for an adequately powered analysis. Here we show for general cognitive ability that, to the contrary, genetic influence increases with age. The heritability of general cognitive ability increases significantly and linearly from 41% in childhood (9 years) to 55% in adolescence (12 years) and to 66% in young adulthood (17 years) in a sample of 11 000 pairs of twins from four countries, a larger sample than all previous studies combined. In addition to its far-reaching implications for neuroscience and molecular genetics, this finding suggests new ways of thinking about the interface between nature and nurture during the school years. Why, despite life's 'slings and arrows of outrageous fortune', do genetically driven differences increasingly account for differences in general cognitive ability? We suggest that the answer lies with genotype-environment correlation: as children grow up, they increasingly select, modify and even create their own experiences in part based on their genetic propensities.

Differential genetic etiology of reading difficulties as a function of IQ: an update.

In order to test the hypothesis that the genetic etiology of reading disability differs as a function of IQ, composite reading performance data from 308 pairs of identical (monozygotic, MZ) twins and 440 pairs of fraternal (dizygotic, DZ) twins (254 same-sex and 186 opposite-sex) in which at least one member of each pair was classified as reading-disabled were subjected to multiple regression analysis (DeFries and Fulker, Behav Genet 15:467-473, 1985; Acta Genet Med Gemellol 37:205-216, 1988). In the total sample, heritability of the group deficit in reading performance (h(g)(2)) was .61 (±.06). However, results of fitting an extended regression model to reading performance and IQ data suggested that the genetic etiology of reading disability differs as a linear function of IQ (p ≤ .04). When the basic regression model was fitted separately to data from twin pairs with Wechsler (Examiner's manual: Wechsler intelligence scale for children-revised, 1974; Examiner's manual: Wechsler adult intelligence scale-revised, 1981) Full Scale IQ scores in the upper and lower 25% of the sample, resulting estimates of h(g)(2) were .75 (±.12) and .50 (±.10), respectively (p ≤ .045). These results suggest that reading difficulties in children with a higher IQ are due substantially to genetic influences and may require intensive remediation efforts.

Assortative mating by unwed biological parents of adopted children.

Analyses of data obtained from 662 unwed couples whose children were relinquished for adoption reveal that biological parents of adopted children mate assortatively. For physical characters, assortative mating of unwed parents was similar to that of wed parents; for behavior characters, however, there was less assortative mating by the unwed parents. Because assortative mating inflates estimates of genetic parameters in adoption studies, future studies should collect information on both biological parents.

Open-field behavior in mice: evidence for a major gene effect mediated by the visual system.

In segregating F(2), F(3), and F(4) generations, albino mice had lower activity and higher defecation scores than pigmented animals when tested in a brightly lighted open field. These differences persisted when members of an F(5) generation were tested under white light, but largely disappeared under red light. Thus it was concluded that there is a major gene effect on the quantitative traits of open-field activity and defecation which is mediated by the visual system and that albino mice are more photophobic than pigmented mice under conditions of bright illumination.

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.

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.

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.

Near identity of cognitive structure in two ethnic groups.

As part of a large-scale family study in Hawaii, Americans of either Japanese or European ancestry were administered a battery of 15 cognitive tests. Principal component analyses (varimax rotations) yielded the same four major cognitive factors for each of the two ethnic groups, and these factors are defined by strikingly similar factor loadings.

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.

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.

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.

A twin study of the etiology of comorbidity: attention-deficit hyperactivity disorder and dyslexia.

Monozygotic and dizygotic twin pairs, in which at least one member of each pair is reading disabled (RD), were assessed for attention-deficit hyperactivity disorder (ADHD). Within pair cross-concordances of the RD and ADHD qualitative diagnoses for monozygotic twins were larger than for dizygotic twins, although not significantly so (p less than 0.10). Thus, the data suggest that RD and ADHD may be primarily genetically independent. However, trends in the data and subtype analyses suggest that in some cases RD and ADHD may occur together because of a shared genetic etiology and that a genetically mediated comorbid subtype may exist.

Components of the GABA system in mice selectively bred for differences in open-field activity.

Mice selectively bred for differences in open-field activity were utilized to test the hypothesis that differences in open-field behaviour are mediated at least in part by components of the GABA system, including brain glutamic acid decarboxylase activity (V, Vmax, and Km), as well as glutamate and GABA concentrations. Enzyme velocity was found to be inversely correlated with open-field activity, but it accounted for less than 15% of the variance. Moreover, the rank order of the lines was not as predicted for a genetically correlated character and the magnitude of the differences in enzyme activity among the lines was not large. It was therefore concluded that the GABA system is not an important mediator of differences in open-field behaviour in these lines of mice.

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.

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.

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.

Colorado reading project: Longitudinal analyses.

Extensive psychometric test data were obtained from two independent samples of reading-disabled and control children: 70 probands and 75 controls tested on two occasions over an average interval of 4.2 years, and 35 probands and 22 controls tested on three occasions over an average interval of 8.6 years. When composite measures of reading performance and symbol-processing speed were subjected to mixed-model multivariate analyses of variance, significant effects due to group (reading-disabled versus control) and time (i.e., test session) were obtained in both samples, and a significant group-by-time interaction was obtained for the sample tested on three occasions. In general, rates of change in reading performance are highly similar for reading-disabled and control children. However, with regard to symbol-processing speed, differences between the two groups increase as a function of age. Although no evidence was obtained for differential longitudinal stability of either composite measure in reading-disabled and control children, results of a multiple regression analysis suggest that reading deficits during middle childhood are highly predictive of later reading problems, even into early adulthood.

Genetic and environmental etiologies of reading disability: A twin study.

Previous twin studies of reading disability employed a comparison of concordance rates in identical and fraternal twin pairs as a test for genetic etiology. Recently, a statistically more powerful multiple regression analysis of twin data has been formulated to assess the importance of genetic factors in the development of reading difficulties. Application of this analysis to twin data from the Colorado Reading Project yields definitive evidence for a genetic etiology. Results from this study suggest that approximately 40 percent of the deficit observed in the disabled readers is due to genetic factors, 35 percent is due to environmental influences shared by members of twin pairs, and about 25 percent is the result of environmental factors unique to the individual and/or error variance.