A genome-wide association study for extremely high intelligence.

We used a case-control genome-wide association (GWA) design with cases consisting of 1238 individuals from the top 0.0003 (~170 mean IQ) of the population distribution of intelligence and 8172 unselected population-based controls. The single-nucleotide polymorphism heritability for the extreme IQ trait was 0.33 (0.02), which is the highest so far for a cognitive phenotype, and significant genome-wide genetic correlations of 0.78 were observed with educational attainment and 0.86 with population IQ. Three variants in locus ADAM12 achieved genome-wide significance, although they did not replicate with published GWA analyses of normal-range IQ or educational attainment. A genome-wide polygenic score constructed from the GWA results accounted for 1.6% of the variance of intelligence in the normal range in an unselected sample of 3414 individuals, which is comparable to the variance explained by GWA studies of intelligence with substantially larger sample sizes. The gene family plexins, members of which are mutated in several monogenic neurodevelopmental disorders, was significantly enriched for associations with high IQ. This study shows the utility of extreme trait selection for genetic study of intelligence and suggests that extremely high intelligence is continuous genetically with normal-range intelligence in the population.

A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence.

Although individual differences in intelligence (general cognitive ability) are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. This study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations. We therefore performed a case-control association analysis with 1409 individuals drawn from the top 0.0003 (IQ >170) of the population distribution of intelligence and 3253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina HumanExome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes. However, analyses using genome-wide similarity between unrelated individuals (genome-wide complex trait analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (s.e. 1.7%) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis. This observation is consistent with the hypothesis that rare functional alleles are more frequently detrimental than beneficial to intelligence.

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.

Top 1 in 10,000: a 10-year follow-up of the profoundly gifted.

Adolescents identified before the age of 13 (N = 320) as having exceptional mathematical or verbal reasoning abilities (top 1 in 10,000) were tracked over 10 years. They pursued doctoral degrees at rates over 50 times base-rate expectations, with several participants having created noteworthy literary, scientific, or technical products by their early 20s. Early observed distinctions in intellectual strength (viz., quantitative reasoning ability over verbal reasoning ability, and vice versa) predicted sharp differences in their developmental trajectories and occupational pursuits. This special population strongly preferred educational opportunities tailored to their precocious rate of learning (i.e., appropriate developmental placement), with 95% using some form of acceleration to individualize their education.

Men and women at promise for scientific excellence: similarity not dissimilarity.

U.S. math-science graduate students possessing world-class talent (368 males, 346 females) were assessed on psychological attributes and personal experiences in order to examine how their talents emerged and developed. Comparisons were made, using similar assessments, with mathematically talented students (528 males, 228 females) identified around age 13 and tracked into adulthood by the Study of Mathematically Precocious Youth (SMPY). Well before college, both samples were academically distinguished: however, the graduate students could be identified during adolescence as a subset of mathematically talented youths based on their nonintellectual attributes. Their profiles corresponded to what earlier psychological studies found to characterize distinguished (and exclusively male) scientists: exceptional quantitative reasoning abilities, relatively stronger quantitative than verbal reasoning ability, salient scientific interests and values, and finally, persistence in seeking out opportunities to study scientific topics and develop scientific skills. On these attributes, sex differences were minimal for the graduate students (but notfor the SMPY comparison groups). Developing exceptional scientific expertise apparently requires special educational experiences, but these necessary experiences are similar for the two sexes.

A genome-wide scan of 1842 DNA markers for allelic associations with general cognitive ability: a five-stage design using DNA pooling and extreme selected groups.

All measures of cognitive processes correlate moderately at the phenotypic level and correlate substantially at the genetic level. General cognitive ability (g) refers to what diverse cognitive processes have in common. Our goal is to identify quantitative trait loci (QTLs) associated with high g compared with average g. In order to detect QTLs of small effect size, we used extreme selected samples and a five-stage design with nominal alpha levels that permit false positive results in early stages but remove false positives in later stages. As a first step toward a systematic genome scan for allelic association, we used DNA pooling to screen 1842 simple sequence repeat (SSR) markers approximately evenly spaced at 2 cM throughout the genome in a five-stage design: (1) case-control DNA pooling (101 cases with mean IQ of 136 and 101 controls with mean IQ of 100), (2) case-control DNA pooling (96 cases with IQ > 160 and 100 controls with mean IQ of 102), (3) individual genotyping of Stage 1 sample, (4) individual genotyping of Stage 2 sample, (5) transmission disequilibrium test (TDT; 196 parent-child trios for offspring with IQ > 160). The over all Type I error rate is 0.000125, which robustly protects against false positive results. The numbers of markers surviving each stage using a conservative allele-specific directional test were 108, 6, 4, 2, and 0, respectively, for the five stages. A genomic control test using DNA pooling suggested that the failure to replicate the positive case-control results in the TDT analysis was not due to ethnic stratification. Several markers that were close to significance at all stages are being investigated further. Relying on indirect association based on linkage disequilibrium between markers and QTLs means that 100,000 markers may be needed to exclude QTL associations. Because power drops off precipitously for indirect association approaches when a marker is not close to the QTL, we are not planning to genotype additional SSR markers. Instead we are using the same design to screen markers such as cSNPs and SNPs in regulatory regions that are likely to include functional polymorphisms in which the marker can be presumed to be the QTL.

Intelligence: success and fitness.

This chapter presents the consensus among psychometricians regarding the construct of general intelligence ('g') and its measurement. More than any other construct, g illustrates the scientific power of construct validation research. To date, g is carried by more assessment vehicles and saturates more aspects of life than any other dimension of human variation uncovered by psychological science. Phenomena most vital to the core of g's nomological network are reviewed (e.g. abstract learning, information processing, and dealing with novelty). This is followed by coverage of relevant but more peripheral phenomena (e.g. crime, health risk behaviour, and income). Because g constitutes such a ubiquitous aspect of the human condition, its omission in social science research often results in underdetermined causal modelling. Frequently, this constitutes a longstanding error in inductive logic, namely, the Fallacy of the Neglected Aspect. Attending to Carnap's Total Evidence Rule can help to forestall neglected aspects in scientific reasoning.

Scientific and social significance of assessing individual differences: "sinking shafts at a few critical points".

This chapter reviews empirical findings on the importance of assessing individual differences in human behavior. Traditional dimensions of human abilities, personality, and vocational interests play critical roles in structuring a variety of important behaviors and outcomes (e.g. achieved socioeconomic status, educational choices, work performance, delinquency, health risk behaviors, and income). In the review of their importance, the construct of general intelligence is featured, but attributes that routinely add incremental validity to cognitive assessments are also discussed. Recent experimental and methodological advances for better understanding how these dimensions may contribute to other psychological frameworks are reviewed, as are ways for determining their scientific significance within domains where they are not routinely assessed. Finally, some noteworthy models are outlined that highlight the importance of assessing relatively distinct classes of individual-differences attributes simultaneously. For understanding fully complex human phenomena such as crime, eminence, and educational-vocational development, such a multifaceted approach is likely to be the most productive.

Sex differences in mathematical reasoning ability at age 13: their status 20 years later.

Reported is the 20-year follow-up of 1,975 mathematically gifted adolescents (top 1%) whose assessments at age 12 to 14 revealed robust gender differences in mathematical reasoning ability. Both sexes became exceptional achievers and perceived themselves as such; they reported uniformly high levels of degree attainment and satisfaction with both their career direction and their overall success. The earlier sex differences in mathematical reasoning ability did predict differential educational and occupational outcomes. The observed differences also appeared to be a function of sex differences in preferences for (a) inorganic versus organic disciplines and (b) a career-focused versus more-balanced life. Because profile differences in abilities and preferences are longitudinally stable, males probably will remain more represented in some disciplines, whereas females are likely to remain more represented in others. These data have policy implications for higher education and the world of work.

States of excellence.

Research from the individual-differences tradition pertinent to the optimal development of exceptional talent is reviewed, using the theory of work adjustment (TWA) to organize fundings. The authors show how TWA concepts and psychometric methods, when used together, can facilitate positive development among talented youth by aligning learning opportunities with salient aspects of each student's individuality. Longitudinal research and more general theoretical models of (adult) academic and intellectual development support this approach. This analysis also uncovers common threads running through several positive psychological concepts (e.g., effectance motivation, flow, and peak experiences). The authors conclude by underscoring some important ideals from counseling psychology for fostering intellectual development and psychological well-being. These include conducting a multifaceted assessment, focusing on strength, helping people make choices, and providing a developmental context for bridging educational and industrial psychology to facilitate positive psychological growth throughout the life span.

DNA pooling identifies QTLs on chromosome 4 for general cognitive ability in children.

General cognitive ability (g), which is related to many aspects of brain functioning, is one of the most heritable traits in neuroscience. Similarly to other heritable quantitatively distributed traits, genetic influence on g is likely to be due to the combined action of many genes of small effect [quantitative trait loci (QTLs)], perhaps several on each chromosome. We used DNA pooling for the first time to search a chromosome systematically with a dense map of DNA markers for allelic associations with g. We screened 147 markers on chromosome 4 such that 85% of the chromosome were estimated to be within 1 cM of a marker. Comparing pooled DNA from 51 children of high g and from 51 controls of average g, 11 significant QTL associations emerged. The association with three of these 11 markers ( D4S2943, MSX1 and D4S1607 ) replicated using DNA pooling in independent samples of 50 children of extremely high g and 50 controls. Furthermore, all three associations were confirmed when each individual was genotyped separately ( D4S2943, P = 0. 00045; MSX1, P = 0.011; D4S1607, P = 0.019). Identifying specific genes responsible for such QTL associations will open new windows in cognitive neuroscience through which to observe pathways between genes and learning and memory.

DNA pooling and dense marker maps: a systematic search for genes for cognitive ability.

Pooling DNA from subjects within a group and comparing the pooled DNA across groups for a dense map of DNA markers offers a solution to the conundrum that linkage is systematic but not powerful whereas allelic association is powerful but not systematic. We used DNA pooling to screen 66 markers on chromosome 22 in original and replication samples of children of high general cognitive ability (g) and controls of average g. Although none of these markers survived our three-stage screening design (original pooling, replication pooling, individual genotyping), the results of DNA pooling were largely confirmed by individual genotyping. We can therefore exclude associations of major effect size on chromosome 22 for g, a key variable for cognitive neuroscience research on learning and memory.

Dopamine markers and general cognitive ability.

Because general cognitive ability (g) is among the most heritable behavioural traits, it is a reasonable target for a search for quantitative trait loci (QTLs). We used a selected-extremes design to test candidate genes for allelic association with g. Polymorphisms in four genes in the dopamine system (DRD2, DRD3, DRD4, DAT1) were genotyped for 51 high g children with IQ scores > 130 and for 51 average g control children. No significant allelic or genotypic differences were found between the high g and average g groups for these markers of the dopamine system, even though the selected-extremes design provides power to detect QTL associations that involve a relative risk of about 1.5.

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.

Arkansas experience: between the government & the private sector.

Officials in many communities, states and regions are trying to establish networks to electronically exchange administrative and clinical data. Today, however, few examples of truly operational healthcare information networks (HINs) exist. Because of governance, control and cost, efforts toward integrating clinical information have not progressed. These issues are most apparent in the struggle to establish community health information networks (CHINs).

Stability of vocational interests among the intellectually gifted from adolescence to adulthood: a 15-year longitudinal study.

A sample of 162 intellectually gifted adolescents (top 1%) were administered the Strong-Campbell Interest Inventory at age 13. Fifteen years later, they were administered the Strong again. This study evaluated the intra- and interindividual temporal stability of the 6 RIASEC (Realistic, Investigative, Artistic, Social, Enterprising, Conventional) themes and the Strong's 23 Basic Interest Scales. Over the 15-year test-retest interval, RIASEC's median interindividual correlation for the 6 themes was .46; the median of all 162 intraindividual correlations was .57. Configural analyses of the most dominant theme at age 13 revealed that this theme was significantly more likely than chance to be either dominant or adjacent to the dominant theme at age 28--following RIASEC's hexagonal structure. For intellectually gifted individuals, it appears to be possible to forecast salient features of their adult RIASEC profile by assessing their vocational interests during early adolescence, but some RIASEC themes seem more stable than others.

Utility of predicting group membership and the role of spatial visualization in becoming an engineer, physical scientist, or artist.

This article has two themes: First, we explicate how the prediction of group membership can augment test validation designs restricted to prediction of individual differences in criterion performance. Second, we illustrate the utility of this methodology by documenting the importance of spatial visualization for becoming an engineer, physical scientist, or artist. This involved various longitudinal analyses on a sample of 400,000 high school students tracked after 11 years following their high school graduation. The predictive validities of Spatial-Math and Verbal-Math ability composites were established by successfully differentiating a variety of educational and occupational groups. One implication of our findings is that physical science and engineering disciplines appear to be losing many talented persons by restricting assessment to conventional mathematical and verbal abilities, such as those of the Scholastic Aptitude Test (SAT) and the Graduate Record Examination (GRE).