Biomedical subjects

Margaret J Wright

Publications and source records attributed to Margaret J Wright.

16 recordsLinked to original sources

PubMed2007

The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence.

Recent studies have made great strides towards identifying putative genetic events underlying the evolution of the human brain and its emergent cognitive capacities. One of the most intriguing findings is the recurrent identification of adaptive evolution in genes associated with primary microcephaly, a developmental disorder characterized by severe reduction in brain size and intelligence, reminiscent of the early hominid condition. This has led to the hypothesis that the adaptive evolution of these genes has contributed to the emergence of modern human cognition. As with other candidate loci, however, this hypothesis remains speculative due to the current lack of methodologies for characterizing the evolutionary function of these genes in humans. Two primary microcephaly genes, ASPM and Microcephalin, have been implicated not only in the adaptive evolution of the lineage leading to humans, but in ongoing selective sweeps in modern humans as well. The presence of both the putatively adaptive and neutral alleles at these loci provides a unique opportunity for using normal trait variation within humans to test the hypothesis that the recent selective sweeps are driven by an advantage in cognitive abilities. Here, we report a large-scale association study between the adaptive alleles of these genes and normal variation in several measures of IQ. Five independent samples were used, totaling 2393 subjects, including both family-based and population-based datasets. Our overall findings do not support a detectable association between the recent adaptive evolution of either ASPM or Microcephalin and changes in IQ. As we enter the post-genomic era, with the number of candidate loci underlying human evolution growing rapidly, our findings highlight the importance of direct experimental validation in elucidating their evolutionary role in shaping the human phenotype.

Adolescent↗

PubMed2006

Replication of reported linkages for dyslexia and spelling and suggestive evidence for novel regions on chromosomes 4 and 17.

We report the first genome-wide linkage analysis for reading and spelling in a sample of 403 families of twins, aged between 12 and 25 years taken from the normal population and unselected for reading ability. These traits showed heritabilities of 0.52-0.73, and support for linkage exceeded replication levels (lod > 1.44) of seven of the 11 linkages reported in dyslexic samples, namely: 2q22.3, 3p12-q13, 6q11.2, 7q32, 15q21.1, 18p21, and Xq27.3. For five of these (2q22.3, 6q11.2, 7q32, 18p21, and Xq27), this study provides the first independent replication. 1p34-36 and 2p15-16 received some support, with lods of 1.2 and 0.83, respectively, whereas two regions received little support (6p23-21.3 and 11p15.5). This study also identified two novel linkages at 4p15.33-16.1 and 17p13.3, which received suggestive support (max. lod 2.08 and 1.99, respectively).

Chromosome Mapping↗

PubMed2006

Heritability and genetic covariation of sensitivity to PROP, SOA, quinine HCl, and caffeine.

The perceived bitterness intensity for bitter solutions of propylthiouracil (PROP), sucrose octa-acetate (SOA), quinine HCl and caffeine were examined in a genetically informative sample of 392 females and 313 males (mean age of 17.8 +/- 3.1 years), including 62 monozygotic and 131 dizygotic twin pairs and 237 sib pairs. Broad-sense heritabilities were estimated at 0.72, 0.28, 0.34, and 0.30 for PROP, SOA, quinine, and caffeine, respectively, for perceived intensity measures. Modeling showed 1) a group factor which explained a large amount of the genetic variation in SOA, quinine, and caffeine (22-28% phenotypic variation), 2) a factor responsible for all the genetic variation in PROP (72% phenotypic variation), which only accounted for 1% and 2% of the phenotypic variation in SOA and caffeine, respectively, and 3) a modest specific genetic factor for quinine (12% phenotypic variation). Unique environmental influences for all four compounds were due to a single factor responsible for 7-22% of phenotypic variation. The results suggest that the perception of PROP and the perception of SOA, quinine, and caffeine are influenced by two distinct sets of genes.

Adolescent↗

PubMed2006

Handedness in twins: joint analysis of data from 35 samples.

Simultaneous analysis of handedness data from 35 samples of twins (with a combined sample size of 21,127 twin pairs) found a small but significant additive genetic effect accounting for 25.47% of the variance (95% confidence interval [CI] 15.69-29.51%). No common environmental influences were detected (C = 0.00; 95% CI 0.00-7.67%), with the majority of the variance, 74.53%, explained by factors unique to the individual (95% CI 70.49-78.67%). No significant heterogeneity was observed within studies that used similar methods to assess handedness, or across studies that used different methods. At an individual level the majority of studies had insufficient power to reject a purely unique environmental model due to insufficient power to detect familial aggregation. This lack of power is seldom mentioned within studies, and has contributed to the misconception that twin studies of handedness are not informative.

Functional Laterality↗

PubMed2005

A linkage study of academic skills defined by the Queensland core skills test.

This study used genome-wide linkage analysis to detect Quantitative Trait Loci (QTLs) implicated in variation in general academic achievement as measured by the Queensland Core Skills Test (QCST) (Queensland Studies Authority, 2004). Data from 210 families were analysed. While no empirically derived significant or suggestive peaks for general academic achievement were indicated a peak on chromosome 2 was observed in a region where Posthuma et al. (2005) reported significant linkage for Performance IQ (PIQ) and suggestive linkage for Full Scale IQ (FSIQ), and Luciano et al. (this issue) observed significant linkage for PIQ and word reading. A peak on chromosome 18 was also observed approximately 20 cM removed from a region recently implicated in reading achievement. In addition, on chromosomes 2 and 18 peaks for a number of specific academic skills, two of which were suggestive, coincided with the general academic achievement peaks. The findings suggest that variation in general academic achievement is influenced by genes on chromosome 2 which have broad influence on a variety of cognitive abilities.

Chromosome Mapping↗

PubMed2005

Genetic variation of individual alpha frequency (IAF) and alpha power in a large adolescent twin sample.

To further clarify the mode of genetic transmission on individual alpha frequency (IAF) and alpha power, the extent to which individual differences in these alpha indices are influenced by genetic factors were examined in a large sample of adolescent twins (237 MZ, 282 DZ pairs; aged 16). EEG was measured at rest (eyes closed) from the right occipital site, and a second EEG recording for 50 twin pairs obtained approximately 3 months after the initial collection, enabled an estimation of measurement error. Analyses confirmed a strong genetic influence on both IAF (h(2)=0.81) and alpha power (h(2)=0.82), and there was little support for non-additive genetic (dominance) variance. A small but significant negative correlation (-0.18) was found between IAF and alpha power, but genetic influences on IAF and alpha power were largely independent. All non-genetic variance was due to unreliability, with no significant variance attributed to unique environmental factors. Relationships between the alpha and IQ indices were also explored but were generally either non-significant or very low. The findings confirm the high heritability for both IAF and alpha power, they further suggest that the mode of genetic transmission is due to additive genetic factors, that genetic influences on the underlying neural mechanisms of alpha frequency and power are largely specific, and that individual differences in alpha activity are influenced little by developmental plasticity and individual experiences.

Adolescent↗

PubMed2005

The genetic basis of academic achievement on the Queensland Core Skills Test and its shared genetic variance with IQ.

First, this study examined genetic and environmental sources of variation in performance on a standardised test of academic achievement, the Queensland Core Skills Test (QCST) (Queensland Studies Authority, 2003a). Second, it assessed the genetic correlation among the QCST score and Verbal and Performance IQ measures using the Multidimensional Aptitude Battery (MAB), [Jackson, D. N. (1984) Multidimensional Aptitude Battery manual. Port Huron, MI:Research Psychologist Press, Inc.]. Participants were 256 monozygotic twin pairs and 326 dizygotic twin pairs aged from 15 to 18 years (mean 17 years+/-0.4 [SD]) when achievement tested, and from 15 to 22 years (mean 16 years+/-0.4 [SD]) when IQ tested. Univariate analysis indicated a heritability for the QCST of 0.72. Adjustment to this estimate due to truncate selection (downward adjustment) and positive phenotypic assortative mating (upward adjustment) suggested a heritability of 0.76 The phenotypic (0.81) and genetic (0.91) correlations between the QCST and Verbal IQ (VIQ) were significantly stronger than the phenotypic (0.57) and genetic (0.64) correlations between the QCST and Performance IQ (PIQ). The findings suggest that individual variation in QCST performance is largely due to genetic factors and that common environmental effects may be substantially accounted for by phenotypic assortative mating. Covariance between academic achievement on the QCST and psychometric IQ (particularly VIQ) is to a large extent due to common genetic influences.

Adolescent↗

PubMed2005

Opposite effects of androgen receptor CAG repeat length on increased risk of left-handedness in males and females.

Prenatal exposure to testosterone has been hypothesised to effect lateralization by influencing cell death in the foetal brain. Testosterone binds to the X chromosome linked androgen receptor, which contains a polymorphic polyglutamine CAG repeat, the length of which is positively correlated with testosterone levels in males, and negatively correlated in females. To determine whether the length of the androgen receptor mediates the effects of testosterone on laterality, we examined the association between the number of CAG repeats in the androgen receptor gene and handedness for writing. Association was tested by adding regression terms for the length of the androgen receptor alleles to a multi-factorial-threshold model of liability to left-handedness. In females we found the risk of left-handedness was greater in those with a greater number of repeats (p=0.04), this finding was replicated in a second independent sample of female twins (p=0.014). The length of the androgen receptor explained 6% of the total variance and 24% of the genetic variance in females. In males the risk of left-handedness was greater in those with fewer repeats (p=0.02), with variation in receptor length explaining 10% of the total variance and 24% of the genetic variance. Thus, consistent with Witelson's theory of testosterone action, in all three samples the likelihood of left handedness increased in those individuals with variants of the androgen receptor associated with lower testosterone levels.

Adult↗

PubMed2005

Perceptual speed does not cause intelligence, and intelligence does not cause perceptual speed.

There is ongoing debate whether the efficiency of local cognitive processes leads to global cognitive ability or whether global ability feeds the efficiency of basic processes. A prominent example is the well-replicated association between inspection time (IT), a measure of perceptual discrimination speed, and intelligence (IQ), where it is not known whether increased speed is a cause or consequence of high IQ. We investigated the direction of causation between IT and IQ in 2012 genetically related subjects from Australia and The Netherlands. Models in which the reliable variance of each observed variable was specified as a latent trait showed IT correlations of -0.44 and -0.33 with respective Performance and Verbal IQ; heritabilities were 57% (IT), 83% (PIQ) and 77% (VIQ). Directional causation models provided poor fits to the data, with covariation best explained by pleiotropic genes (influencing variation in both IT and IQ). This finding of a common genetic factor provides a better target for identifying genes involved in cognition than genes which are unique to specific traits.

Adolescent↗

PubMed2005

Psychological masculinity-femininity via the gender diagnosticity approach: heritability and consistency across ages and populations.

Several aspects of the Gender Diagnosticity (GD) approach of Lippa (1995) to measuring the psychological trait of masculinity-femininity within sexes were explored in four samples ranging from 363 to 5,859 individuals, including Swedish and Australian adults, U.S. elderly, and Australian adolescents. Two ways of deriving GD scales yielded highly similar results. Moderate stability of individual differences was found across ages 12 to 16 among adolescents, but substantial shifts over age occurred in relationships with Eysenck scales. Considerable generality of GD scales was obtained across languages and populations. Substantial heritabilities (about 40%) and minimal effects of shared family environments suggest that within-sex masculinity-femininity behaves as a fairly typical personality trait. Cross-age continuity appeared mainly to reflect the influence of the genes.

Adolescent↗

PubMed2005

Multivariate genetic analysis of academic skills of the Queensland core skills test and IQ highlight the importance of genetic g.

This study examined the genetic and environmental relationships among 5 academic achievement skills of a standardized test of academic achievement, the Queensland Core Skills Test (QCST; Queensland Studies Authority, 2003a). QCST participants included 182 monozygotic pairs and 208 dizygotic pairs (mean 17 years +/- 0.4 standard deviation). IQ data were included in the analysis to correct for ascertainment bias. A genetic general factor explained virtually all genetic variance in the component academic skills scores, and accounted for 32% to 73% of their phenotypic variances. It also explained 56% and 42% of variation in Verbal IQ and Performance IQ respectively, suggesting that this factor is genetic g. Modest specific genetic effects were evident for achievement in mathematical problem solving and written expression. A single common factor adequately explained common environmental effects, which were also modest, and possibly due to assortative mating. The results suggest that general academic ability, derived from genetic influences and to a lesser extent common environmental influences, is the primary source of variation in component skills of the QCST.

Adolescent↗

PubMed2004

A genetic investigation of the covariation among inspection time, choice reaction time, and IQ subtest scores.

Information processing speed, as measured by elementary cognitive tasks, is correlated with higher order cognitive ability so that increased speed relates to improved cognitive performance. The question of whether the genetic variation in Inspection Time (IT) and Choice Reaction Time (CRT) is associated with IQ through a unitary factor was addressed in this multivariate genetic study of IT, CRT, and IQ subtest scores. The sample included 184 MZ and 206 DZ twin pairs with a mean age of 16.2 years (range 15-18 years). They were administered a visual (pi-figure) IT task, a two-choice RT task, five computerized subtests of the Multidimensional Aptitude Battery, and the digit symbol substitution subtest from the WAIS-R. The data supported a factor model comprising a general, three group (verbal ability, visuospatial ability, broad speediness), and specific genetic factor structure, a shared environmental factor influencing all tests but IT, plus unique environmental factors that were largely specific to individual measures. The general genetic factor displayed factor loadings ranging between 0.35 and 0.66 for the IQ subtests, with IT and CRT loadings of -0.47 and -0.24, respectively. Results indicate that a unitary factor is insufficient to describe the entire relationship between cognitive speed measures and all IQ subtests, with independent genetic effects explaining further covariation between processing speed (especially CRT) and Digit Symbol.

Adolescent↗

PubMed2004

Genetic and environmental sources of covariance between reading tests used in neuropsychological assessment and IQ subtests.

In this study, we examined genetic and environmental influences on covariation among two reading tests used in neuropsychological assessment (Cambridge Contextual Reading Test [CCRT], [Beardsall, L., and Huppert, F. A. (1994). J. Clin. Exp. Neuropsychol. 16:232-242], Schonell Graded Word Reading Test [SGWRT], [Schonell, F. J., and Schonell, P. E. (1960). Diagnostic and attainment testing. Edinburgh: Oliver and Boyd.]) and among a selection of IQ subtests from the Multidimensional Aptitude Battery (MAB), [Jackson, D. N. (1984). Multidimensional aptitude battery, Ontario: Research Psychologists Press.] and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) [Wechsler, D. (1981). Manual for the Wechsler Adult Intelligence Scale-Revised (WAIS-R). San Antonio: The Psychological Corporation]. Participants were 225 monozygotic and 275 dizygotic twin pairs aged from 15 years to 18 years (mean, 16 years). For Verbal IQ subtests, phenotypic correlations with the reading tests ranged from 0.44 to 0.65. For Performance IQ subtests, phenotypic correlations with the reading tests ranged from 0.23 to 0.34. Results of Structural Equation Modeling (SEM) supported a model with one genetic General factor and three genetic group factors (Verbal, Performance, Reading). Reading performance was influenced by the genetic General factor (accounting for 13% and 20% of the variance for the CCRT and SGWRT, respectively), the genetic Verbal factor (explaining 17% and 19% of variance for the CCRT and SGWRT), and the genetic Reading factor (explaining 21% of the variance for both the CCRT and SGWRT). A common environment factor accounted for 25% and 14% of the CCRT and SGWRT variance, respectively. Genetic influences accounted for more than half of the phenotypic covariance between the reading tests and each of the IQ subtests. The heritabilities of the CCRT and SGWRT were 0.54 and 0.65, respectively. Observable covariance between reading assessments used by neuropsychologists to estimate IQ and IQ subtests appears to be largely due to genetic effects.

Adolescent↗

PubMed2004

Exploring the etiology of the association between birthweight and IQ in an adolescent twin sample.

The negative effects of very low birthweight on intellectual development have been well documented, and more recently this effect has been shown to generalize to birthweights within the normal range. In this study we investigate the etiology of this relationship by using a classical twin design to disentangle the contributions of genes and environment. A previous Dutch study (Boomsma et al., 2001) examining these effects indicated that genes were important in mediating the association of birthweight to full IQ measured at ages 7 and 10, but not at ages 5 and 12. Here the association between birthweight and IQ at age 16 is considered (N = 523 twin pairs). Using variance components modeling we found that the genetic variance in birthweight (4%) completely overlapped with that in verbal IQ but not performance or full IQ. Results further showed the importance of shared environmental effects on birthweight (~ 60%) but not on IQ (with genes explaining up to 72% of IQ variance). Models incorporating a direction of causation parameter between birthweight and IQ provided adequate fit to the data in either causal direction for performance and full IQ, but the model with verbal IQ causing birthweight was preferred to one in which birthweight influenced verbal IQ. As the measurement of birthweight precedes the measurement of twins' IQ at age 16, the influence of verbal IQ might be better considered as a proxy for parents' IQ or education, and it is possible that brighter mothers provide better prenatal environments for their children.

Adolescent↗

PubMed2003

Special twin environments, genetic influences and their effects on the handedness of twins and their siblings.

It has been suggested that twinning may influence handedness through the effects of birth order, intra-uterine crowding and mirror imaging. The influence of these effects on handedness (for writing and throwing) was examined in 3657 Monozygotic (MZ) and 3762 Dizygotic (DZ) twin pairs (born 1893-1992). Maximum likelihood analyses revealed no effects of birth order on the incidence of left-handedness. Twins were no more likely to be left-handed than their singleton siblings (n = 1757), and there were no differences between the DZ co-twin and sibling-twin covariances, suggesting that neither intra-uterine crowding nor the experience of being a twin affects handedness. There was no evidence of mirror imaging; the co-twin correlations of monochorionic and dichorionic MZ twins did not differ. Univariate genetic analyses revealed common environmental factors to be the most parsimonious explanation of familial aggregation for the writing-hand measure, while additive genetic influences provided a better interpretation of the throwing hand data.

Birth Order↗

PubMed2002

Genetic sources of covariation among P3(00) and online performance variables in a delayed-response working memory task.

Genetic and environmental sources of covariation among the P3(00) and online performance elicited in a delayed-response working memory task, and psychometric IQ assessed by the multidimensional aptitude battery, were examined in an adolescent twin sample. An association between frontal P3 latency and task performance (phenotypic r=-0.33; genotypic r=-0.49) was indicated, with genes (i.e. twin status) accounting for a large part of the covariation (>70%). In contrast, genes influencing P3 amplitude mediated only a small part (2%) of the total genetic variation in task performance. While task performance mediated 15% of the total genetic variation in IQ (phenotypic r=0.22; genotypic r=0.39) there was no association between P3 latency and IQ or P3 amplitude with IQ. The findings provide some insight into the inter-relationships among psychophysiological, performance and psychometric measures of cognitive ability, and provide support for a levels-of-processing genetic model of cognition where genes act on specific sub-components of cognitive processes.

Adolescent↗