Why do we differ in number sense? Evidence from a genetically sensitive investigation.

Basic intellectual abilities of quantity and numerosity estimation have been detected across animal species. Such abilities are referred to as 'number sense'. For human species, individual differences in number sense are detectable early in life, persist in later development, and relate to general intelligence. The origins of these individual differences are unknown. To address this question, we conducted the first large-scale genetically sensitive investigation of number sense, assessing numerosity discrimination abilities in 837 pairs of monozygotic and 1422 pairs of dizygotic 16-year-old twin pairs. Univariate genetic analysis of the twin data revealed that number sense is modestly heritable (32%), with individual differences being largely explained by non-shared environmental influences (68%) and no contribution from shared environmental factors. Sex-Limitation model fitting revealed no differences between males and females in the etiology of individual differences in number sense abilities. We also carried out Genome-wide Complex Trait Analysis (GCTA) that estimates the population variance explained by additive effects of DNA differences among unrelated individuals. For 1118 unrelated individuals in our sample with genotyping information on 1.7 million DNA markers, GCTA estimated zero heritability for number sense, unlike other cognitive abilities in the same twin study where the GCTA heritability estimates were about 25%. The low heritability of number sense, observed in this study, is consistent with the directional selection explanation whereby additive genetic variance for evolutionary important traits is reduced.

A genome-wide association study identifies multiple loci associated with mathematics ability and disability.

Numeracy is as important as literacy and exhibits a similar frequency of disability. Although its etiology is relatively poorly understood, quantitative genetic research has demonstrated mathematical ability to be moderately heritable. In this first genome-wide association study (GWAS) of mathematical ability and disability, 10 out of 43 single nucleotide polymorphism (SNP) associations nominated from two high- vs. low-ability (n = 600 10-year-olds each) scans of pooled DNA were validated (P < 0.05) in an individually genotyped sample of (*)2356 individuals spanning the entire distribution of mathematical ability, as assessed by teacher reports and online tests. Although the effects are of the modest sizes now expected for complex traits and require further replication, interesting candidate genes are implicated such as NRCAM which encodes a neuronal cell adhesion molecule. When combined into a set, the 10 SNPs account for 2.9% (F = 56.85; df = 1 and 1881; P = 7.277e-14) of the phenotypic variance. The association is linear across the distribution consistent with a quantitative trait locus (QTL) hypothesis; the third of children in our sample who harbour 10 or more of the 20 risk alleles identified are nearly twice as likely (OR = 1.96; df = 1; P = 3.696e-07) to be in the lowest performing 15% of the distribution. Our results correspond with those of quantitative genetic research in indicating that mathematical ability and disability are influenced by many genes generating small effects across the entire spectrum of ability, implying that more highly powered studies will be needed to detect and replicate these QTL associations.

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.

Generalist genes and the Internet generation: etiology of learning abilities by web testing at age 10.

A key translational issue for neuroscience is to understand how genes affect individual differences in brain function. Although it is reasonable to suppose that genetic effects on specific learning abilities, such as reading and mathematics, as well as general cognitive ability (g), will overlap very little, the counterintuitive finding emerging from multivariate genetic studies is that the same genes affect these diverse learning abilities: a Generalist Genes hypothesis. To conclusively test this hypothesis, we exploited the widespread access to inexpensive and fast Internet connections in the UK to assess 2541 pairs of 10-year-old twins for reading, mathematics and g, using a web-based test battery. Heritabilities were 0.38 for reading, 0.49 for mathematics and 0.44 for g. Multivariate genetic analysis showed substantial genetic correlations between learning abilities: 0.57 between reading and mathematics, 0.61 between reading and g, and 0.75 between mathematics and g, providing strong support for the Generalist Genes hypothesis. If genetic effects on cognition are so general, the effects of these genes on the brain are also likely to be general. In this way, generalist genes may prove invaluable in integrating top-down and bottom-up approaches to the systems biology of the brain.

Overlap and specificity of genetic and environmental influences on mathematics and reading disability in 10-year-old twins.

BACKGROUND: To what extent do genetic and environmental influences on reading disability overlap with those on mathematics disability? Multivariate genetic research on the normal range of variation in unselected samples has led to a Generalist Genes Hypothesis which posits that the same genes largely affect individual differences in these abilities in the normal range. However, little is known about the etiology of co-morbidity for the disability extremes of reading and mathematics. METHOD: From 2596 pairs of 10-year-old monozygotic and dizygotic twins assessed on a web-based battery of reading and mathematics tests, we selected the lowest 15% on reading and on mathematics. We conducted bivariate DeFries-Fulker (DF) extremes analyses to assess overlap and specificity of genetic and environmental influences on reading and mathematics disability defined by a 15% cut-off. RESULTS: Both reading and mathematics disability are moderately heritable (47% and 43%, respectively) and show only modest shared environmental influence (16% and 20%). There is substantial phenotypic co-morbidity between reading and mathematics disability. Bivariate DF extremes analyses yielded a genetic correlation of .67 between reading disability and mathematics disability, suggesting that they are affected largely by the same genetic factors. The shared environmental correlation is .96 and the non-shared environmental correlation is .08. CONCLUSIONS: In line with the Generalist Genes Hypothesis, the same set of generalist genes largely affects mathematical and reading disabilities. The dissociation between the disabilities occurs largely due to independent non-shared environmental influences.

The Origins of Diverse Domains of Mathematics: Generalist Genes but Specialist Environments.

The authors assessed 2,502 ten-year-old children, members of 1,251 pairs of twins, on a Web-based battery of problems from 5 diverse aspects of mathematics assessed as part of the U.K. national curriculum. This 1st genetic study into the etiology of variation in different domains of mathematics showed that the heritability estimates were moderate and highly similar across domains and that these genetic influences were mostly general. Environmental factors unique to each twin in a family (rather than shared by the 2 twins) explained most of the remaining variance, and these factors were mostly specific to each domain.

'Generalist genes' and mathematics in 7-year-old twins.

Mathematics performance at 7 years as assessed by teachers using UK national curriculum criteria has been found to be highly heritable. For almost 3000 pairs of 7-year-old same-sex twins, we used multivariate genetic analysis to investigate the extent to which these genetic effects on mathematics performance overlap with genetic effects on reading and general intelligence (g) as predicted by the 'generalist genes' hypothesis. We found substantial genetic overlap between mathematics and reading (genetic correlation=0.74) and between mathematics and g (0.67). These findings support the 'generalist genes' hypothesis that most of the genes that contribute to individual differences in mathematics are the same genes that affect reading and g. Nonetheless, the genetic correlations are less than unity and about a third of the genetic variance on mathematics is independent of reading and g, suggesting that there are also some genes whose effects are specific to mathematics.

Infant zygosity can be assigned by parental report questionnaire data.

A parental report questionnaire posted to a population sample of 18-month-old twins correctly assigned zygosity in 95%of cases when validated against zygosity determined by identity of polymorphic DNA markers. The questionnaire was as accurate when readministered at 3 years of age, with 96% of children being assigned the same zygosity on both occasions. The results validate the use of parental report questionnaire data to determine zygosity in infancy.

One-year use and cost of inpatient and outpatient services among female and male patients with an eating disorder: evidence from a national database of health insurance claims.

OBJECTIVE: This study examined rates and cost of inpatient and outpatient treatment among 1,932 patients with an eating disorder. METHOD: One-year (1995) data were available through MarketScan, a national insurance database containing claims for 1,902,041 male patients and 2,005,760 female patients. RESULTS: Female patients (n = 1,756, 0.14% of all females) were significantly more likely to have been treated for an eating disorder than male patients (n = 176, 0.016% of all males), and females received more days of treatment than males. Outpatient treatment was the norm, regardless of gender or type of eating disorder. Average number of days (inpatient or outpatient) was less than the minimum recommended by standards of care. Age-adjusted costs for the treatment of anorexia nervosa and bulimia nervosa were comparable to the cost of treatment for schizophrenia. DISCUSSION: The utilization data are discussed in terms of barriers to care and treatment guidelines for eating disorders.

Genetic and environmental origins of verbal and performance components of cognitive delay in 2-year-olds.

The authors investigated the etiology of several measures of cognitive delay. Verbal (V) and performance (P) abilities were assessed in over 3,000 pairs of 2-year-old twins. Group-differences heritability for general delay (the lowest 5% of the V and P composite) was 35%. However, V and P delays considered independently showed large differences in group heritability (77% for V vs. 40% for P). Specific delays with comorbid cases eliminated showed an even greater difference in group heritability (78% vs. 22%, respectively). The small sample comorbid for both V and P delay also yielded high group heritability for both V (77%) and P (93%) scores. Shared environmental factors also differed in magnitude for V (20%) and P (41%) delays. Because the genetic and environmental origins of V and P delays in infancy differ, they are better considered separately rather than combined into a composite measure of general cognitive delay.

Exploring the genetic and environmental etiology of high general cognitive ability in fourteen- to thirty-six-month-old twins.

Although numerous theories have attempted to explain the origins of high general cognitive ability (g), the genetic and environmental etiology of high g during infancy and early childhood has not previously been investigated. We report results of a twin study of high cognitive ability at 14, 20, 24, and 36 months using twins from the more than 600 children participating in the MacArthur Longitudinal Twin Study. High g groups were formed from the ninetieth percentile and above at each age, with IQ equivalent means at or above 126 across the ages. Results suggest increasing genetic influence and increasing genetic stability from 14 to 36 months using DeFries-Fulker multiple regression analyses. However, genetic influences are substantial when examining individuals who possess high g scores averaged across all 4 ages. These results suggest that, although high cognitive ability may be genetically influenced in early childhood, these influences differ in magnitude from 14 to 36 months.

Substantial genetic influence on cognitive abilities in twins 80 or more years old.

General and specific cognitive abilities were studied in intact Swedish same-sex twin pairs 80 or more years old for whom neither twin had major cognitive, sensory, or motor impairment. Resemblance for 110 identical twin pairs significantly exceeded resemblance for 130 fraternal same-sex twin pairs for all abilities. Maximum-likelihood model-fitting estimates of heritability were 62 percent for general cognitive ability, 55 percent for verbal ability, 32 percent for spatial ability, 62 percent for speed of processing, and 52 percent for memory. There was also evidence for the significant influence of idiosyncratic experience as the environmental component that most determines individual differences in cognitive abilities late in life.

Exploring the genetic etiology of low general cognitive ability from 14 to 36 months.

The genetic and environmental etiology of low general cognitive ability (g) during infancy and early childhood has not previously been investigated. The current study examined the genetic etiology of low cognitive ability at 14, 20, 24, and 36 months with twins from the MacArthur Longitudinal Twin Study. Low g groups were formed from the lowest 10th percentile at each age. Univariate probandwise concordance rates and DeFries-Fulker (J. C. DeFries & D. W. Fulker, 1985, 1988) multiple regression techniques suggest genetic etiology in low general cognitive ability groups. The stability of low general cognitive ability over time also appears to be primarily due to genetic factors. Although replication is necessary, these results suggest that the genetic etiology of low g during infancy and early childhood is at least as great as the heritability of g in the unselected population.

No association between general cognitive ability and the A1 allele of the D2 dopamine receptor gene.

Berman and Noble (1995) reported significantly reduced visuospatial performance in children with the TAQI A1 allele of the D2 dopamine receptor (DRD2) gene. Given that visuospatial performance loads highly on an unrotated principal component indexing general cognitive ability, we tested the association between DRD2 and WISC-R IQ comparing 51 high-IQ, 51 average-IQ, and 35 low-IQ children in the IQ Quantitative Trait Loci (QTL) Project. No statistically significant association between the TAQI A DRD2 alleles and IQ was found. Given that a statistically significant portion of genetic variance for specific cognitive abilities is independent of general cognitive ability, it is possible that the TAQI DRD2 association is specific to visuospatial performance and independent of general cognitive ability.

The independent prediction of general intelligence by elementary cognitive tasks: genetic and environmental influences.

Current theories of intelligence have, in some cases, begun to include elementary cognitive tasks. Behavioral genetic studies of intelligence have not taken these theories into account. The current study includes 135 MZ and 128 DZ twin pairs from the Western Reserve Twin Project. The 11 WISC-R subtests as well as 6 elementary cognitive tasks were employed. Using a Schmid-Leiman (1957) transformation, analyses indicate a four-group factor model, supported by a second-order general factor at both phenotypic and biometric levels. Results indicate that the general factor, group factors, and specific residuals are necessary when examining additive genetic variance. Common environmental variance can be collapsed into a single general factor.

The genetic and environmental variance underlying elementary cognitive tasks.

Although previous studies have examined the genetic and environmental influences upon general intelligence and specific cognitive abilities in school-age children, few studies have examined elementary cognitive tasks in this population. The current study included 149 MZ and 138 same-sex DZ twin pairs who participated in the Western Reserve Twin Project. Thirty measures from the Cognitive Abilities Test (CAT; Detterman, 1986) were studied. Results indicate that (1) these measures are reliable indicators of general intelligence in children and (2) the structure of genetic and environmental influences varies across measures. These results not only indicate that elementary cognitive tasks display heterogeneous genetic and environmental effects, but also may demonstrate that individual differences in biologically based processes are not necessarily due to genetic variance.

Gender differences in language of AD patients: a longitudinal study.

We examined gender differences in probable Alzheimer's disease (AD) patients on language measures at four data collections (entry, 6, 12, and 18 months) and a normal elderly (NE) comparison group at entry and 18 months. Comparison of gender differences in language abilities of 60 (29 men, 31 women) early (Clinical Dementia Ratings I and II) AD subjects at entry revealed significant effects for gender on the Boston Naming Test (BNT) and Peabody Picture Vocabulary Test-Revised (PPVT-R) but not on the Word Fluency Test, shortened Token Test, or modified Reporter's Test. The 37 subjects (18 men, 19 women) who completed less than four data collection sessions compared with the 23 subjects (11 men, 12 women) who completed all four sessions differed on education and Reporter's Test scores. Longitudinal analysis of measures showed that gender differences persisted for the BNT and PPVT-R and that time differences were found on all measures. Gender differences remained after correcting for age, education, duration of illness, and mental status. We found no differences for the NE comparison group for gender or time. All AD subject trends were downward, suggesting that (1) language is affected over time in AD, (2) both men and women decline at similar rates, and (3) language abilities of women are more severely impaired at all time points.

The heritability of memory in the Western Reserve Twin Project.

The heritability of memory ability was examined using 137 monozygotic and 127 same-sex dizygotic twin pairs from the Western Reserve Twin Project. Memory was assessed by eight measures drawn from the following batteries: the Wechsler Intelligence Scale for Children--Revised, the Colorado Test of Specific Cognitive Abilities, and the Cognitive Abilities Test. The results indicate that phenotypic correlations are generally low across these memory measures and heritability varies as a function of memory measure. These findings suggest that the heritability of memory varies as a function of the memory measure employed. Therefore, future studies investigating heritability estimates of memory should use a multimeasure battery to study this construct.

The phenotypic and genetic relationships among measures of cognitive ability, temperament, and scholastic achievement.

The covariance among measures of cognitive ability, temperament, and scholastic achievement was examined in a subsample of 326 (89 Monozygotic, 74 Dizygotic) twins drawn from the Western Reserve Twin Project. Both phenotypic and behavioral genetic models were fit to the data. Univariate analyses indicate significant genetic influences on cognitive, achievement, and temperament variables. Common environmental influences also affected cognition and achievement but not temperament. Multivariate analyses indicate that both genetic and common environmental influences contribute to the covariance among all three variables. Cognition and achievement are highly genetically correlated. In contrast, achievement and temperament are highly correlated for common environmentality, while cognition and temperament are not.