229 resultados para Multivariate Genetic Modeling

em University of Queensland eSpace - Australia


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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.

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The sources of covariation among cognitive measures of Inspection Time, Choice Reaction Time, Delayed Response Speed and Accuracy, and IQ were examined in a classical twin design that included 245 monozygotic (MZ) and 298 dizygotic (DZ) twin pairs. Results indicated that a factor model comprising additive genetic and unique environmental effects was the most parsimonious. In this model, a general genetic cognitive factor emerged with factor loadings ranging from 0.28 to 0.64. Three other genetic factors explained the remaining genetic covariation between various speed and Delayed Response measures with IQ. However, a large proportion of the genetic variation in verbal (54%) and performance (25%) IQ was unrelated to these lower order cognitive measures. The independent genetic IQ variation may reflect information processes not captured by the elementary cognitive tasks, Inspection Time and Choice Reaction Time, nor our working memory task, Delayed Response. Unique environmental effects were mostly nonoverlapping, and partly represented test measurement error.

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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.

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The phenotypic and genetic factor structure of performance on five Multidimensional Aptitude Battery (MAB) subtests and one Wechsler Adult Intelligence Scale-Revised (WAIS-R) subtest was explored in 390 adolescent twin pairs (184 monozygotic [MZ]; 206 dizygotic (DZ)). The temporal stability of these measures was derived from a subsample of 49 twin pairs, with test-retest correlations ranging from .67 to .85. A phenotypic factor model, in which performance and verbal factors were correlated, provided a good fit to the data. Genetic modeling was based on the phenotypic factor structure, but also took into account the additive genetic (A), common environmental (C), and unique environmental (E) parameters derived from a fully saturated ACE model. The best fitting model was characterized by a genetic correlated two-factor structure with specific effects, a general common environmental factor, and overlapping unique environmental effects. Results are compared to multivariate genetic models reported in children and adults, with the most notable difference being the growing importance of common genes influencing diverse abilities in adolescence. (C) 2003 Elsevier Inc. All rights reserved.

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Previous genetic analyses of psychosis proneness have been limited by their small sample size. For the purposes of large-scale screening, a 12-item questionnaire was developed through a two-stage process of reduction from the full Chapman and Chapman scales. 3685 individuals (including 1438 complete twin pairs) aged 18–25 years and enrolled in the volunteer Australian Twin Registry returned a mail questionnaire which included this psychosis proneness scale and the Eysenck Personality Questionnaire. Despite the brevity of the questionnaire, item and factor analysis identified four unambiguous and essentially uncorrelated scales. There were (1) Perceptual Aberration – Magical Ideation; (2) Hypomania – Impulsivity/Nonconformity; (3) Social Anhedonia and (4) Physical Anhedonia. Model-fitting analyses showed additive genetic and specific environmental factors were sufficient for three of the four scales, with the Social Anhedonia scale requiring also a parameter for genetic dominance. There was no evidence for the previously hypothesised sex differences in the genetic determination of psychosis-proneness. The potential value of multivariate genetic analysis to examine the relationship between these four scales and dimensions of personality is discussed. The growing body of longitudinal evidence on psychosis-proneness suggests the value of incorporating this brief measure into developmental twin studies.

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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.

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The dopamine D4 receptor gene contains a polymorphic sequence consisting of a variable number of 48-base-pair (bp) repeats, and there have been a number of reports that this polymorphism is associated with variation in novelty seeking or in substance abuse and addictive behaviors. In this study we have assessed the linkage and association of DRD4 genotype with novelty seeking, alcohol use, and smoking in a sample of 377 dizygotic twin pairs and 15 single twins recruited from the Australian Twin Registry (ATR). We found no evidence of linkage or association of the DRD4 locus with any of the phenotypes. We made use of repeated measures for some phenotypes to increase power by multivariate genetic analysis, but allelic effects were still non-significant. Specifically, it has been suggested that the DRD4 7-repeat allele is associated with increased novelty seeking in males but we found no evidence for this, despite considerable power to do so. We conclude that DRD4 variation does not have an effect on use of alcohol and the problems that arise from it, on smoking, or on novelty seeking behavior. (C) 2003 Wiley-Liss, Inc.

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Background. We examined whether there are genetic influences on nicotine withdrawal. and whether there are genetic factors specific to nicotine withdrawal, after controlling for factors responsible for risk of progression beyond experimentation with cigarettes and for quantity smoked (average number of cigarettes per day at peak lifetime use). Method. Epidemiologic and genetic analyses were conducted using telephone diagnostic interview data from Young adult Australian twins reporting any cigarette use (3026 women. 2553 men: mean age 30 years). Results. Genetic analysis of the eight symptoms of DSM-IV nicotine withdrawal suggests heritability is intermediate for most symptoms (26-43%). and Similar in men and women. The exceptions were depressed mood upon withdrawal. which had stronger additive genetic influences in men (53%) compared to worrien (29%). and decreased heart rate. which had low heritability (9%). Although prevalence rates were substantlally lower for DSM-IV nicotine withdrawal syndrome (15-9%), which requires impairment. than for the DSM-IV nicotine dependence withdrawal criterion (43.6%), heritability was similar for both measures: as high as 47%. Genetic modeling of smoking more than 1 or 2 cigarettes lifetime ('progression'). qualtity smoked and nicotine withdrawal found significant genetic overlap across all three components of nicotine use/dependence (genetic correlations = 0.53-0.76). Controlling for factors associated with risk of cigarette smoking beyond experimentation and quantity smoked, evidence for genetic influences specific to nicotine withdrawal (up to 23% of total variance) remained. Conclusions. Our results suggest that at least some individuals become 'hooked' or progress in the smoking habit, in part, because of it vulnerability to nicotine withdrawal.

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Intelligence (IQ) can be seen as the efficiency of mental processes or cognition, as can basic information processing (IP) tasks like those used in our ongoing Memory, Attention and Problem Solving (MAPS) study. Measures of IQ and IP are correlated and both have a genetic component, so we are studying how the genetic variance in IQ is related to the genetic variance in IP. We measured intelligence with five subscales of the Multidimensional Aptitude Battery (MAB). The IP tasks included four variants of choice reaction time (CRT) and a visual inspection time (IT). The influence of genetic factors on the variances in each of the IQ, IP, and IT tasks was investigated in 250 identical and nonidentical twin pairs aged 16 years. For a subset of 50 pairs we have test–retest data that allow us to estimate the stability of the measures. MX was used for a multivariate genetic analysis that addresses whether the variance in IQ and IP measures is possibly mediated by common genetic factors. Analyses that show the modeled genetic and environmental influences on these measures of cognitive efficiency will be presented and their relevance to ideas on intelligence will be discussed.

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As part of a large ongoing project, the Memory, Attention and Problem Solving (MAPS) study, we investigated whether genetic variability explains some of the variance in psychophysiological correlates of brain function, namely, the P3 and SW components of event-related potentials (ERPs). These ERP measures are minute time recordings of brain processes and, because they reflect fundamental cognitive processing, provide a unique window on the millisecondto- millisecond transactions that occur at the cognitive level and taking place in the human brain. The extent to which the variance in P3 and SW components is influenced by genetic factors was examined in 350 identical and nonidentical twin pairs aged 16 years. ERPs were recorded from 15 scalp electrodes during the performance of a visuospatial delayed response task that engages working memory. Multivariate genetic analyses using MX were used to estimate genetic and environmental influences on individual differences in brain functioning and to identify putative genetic factors common to the ERP measures and psychometric IQ. For each of the ERP measures, correlation among electrode sites was high, a spatial pattern was evident, and a large part of the genetic variation in the ERPs appeared to be mediated by a common genetic factor. Moderate within-pair concordance in MZ pairs was found for all ERP measures, with higher correlations found for P3 than SW, and the MZ twin pair correlations were approximately twice the DZ correlations, suggesting a genetic influence. Correlations between ERP measures and psychometric IQ were found and, although moderately low, were evident across electrode site. The analyses show that the ERP components, P3 and SW, are promising phenotypes of the neuroelectrical activity of the brain and have the potential to be used in linkage and association analysis in the search for QTLs influencing cognitive function.

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Risk factors to prolonged fatigue syndromes (PFS) are controversial. Pre-morbid and/or current psychiatric disturbance, and/or disturbed cell-mediated immunity (CMI), have been proposed as etiologic factors. Self-report measures of fatigue and psychologic distress and three in vitro measures of CMI were collected from 124 twin pairs. Crosstwincrosstrait correlations were estimated for the complete monozygotic (MZ; 79 pairs) and dizygotic (DZ; 45 pairs) twin groups. Multivariate genetic and environmental models were fitted to explore the patterns of covariation between etiologic factors. For fatigue, the MZ correlation was more than double the DZ correlation (0.49 versus 0.16) indicating strong genetic control of familial aggregation. By contrast, for in vitro immune activation measures MZ and DZ correlations were similar (0.49–0.69 versus 0.42–0.53) indicating the etiologic role of shared environments. As small univariate associations were noted between prolonged fatigue and the in vitro immune measures (r = −0.07 to −0.12), multivariate models were fitted. Relevant etiologic factors included: a common genetic factor accounting for 48% of the variance in fatigue which also accounted for 4%, 6% and 8% reductions in immune activation; specific genetic factors for each of the in vitro immune measures; a shared environment factor influencing the three immune activation measures; and, most interestingly, unique environmental influences which increased fatigue but also increased markers of immune activation. PFS that are associated with in vitro measures of immune activation are most likely to be the consequence of current environmental rather than genetic factors. Such environmental factors could include physical agents such as infection and/or psychologic stress.

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Although cannabis is the most commonly used illicit drug, duration of cannabis use is typically short, with many of those who initiate cannabis use ceasing use by their late twenties. In this paper we analyze data from a volunteer Australian cohort of 6265 male and female twins to examine whether the duration of cannabis use is an informative phenotype for future genetic analyses. Genetic modeling indicated: (a) moderate genetic influences on duration of cannabis use in both males (41%; 95% CI = 31–51) and females (55%; 95% CI = 46–63); (b) strong genetic influences on cannabis dependence in both males (72%, 95% CI = 61–81) and females (62%, 95% CI = 48–74); (c) no evidence of shared environmental influences on duration of cannabis use or on cannabis dependence in either males or females. Importantly, this model fitting indicated that a substantial component of genetic influences (rg = .90, 95% CI = .77–.99 (males); .70, 95% CI = .57–.83 (females)) on duration of cannabis use was shared with those influencing liability to cannabis dependence. While there were high genetic correlations in both women and men, lifetime duration of cannabis may be uniquely informative in assessing components of liability to cannabis use.

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While it is well known that reading is highly heritable, less has been understood about the bases of these genetic influences. In this paper, we review the research that we have been conducting in recent years to examine genetic and environmental influences on the particular reading processes specified in the dual-route cognitive model of reading. We argue that a detailed understanding of the role of genetic factors in reading acquisition requires the delineation and measurement of precise phenotypes, derived from well-articulated models of the reading process. We report evidence for independent genetic influences on the lexical and nonlexical reading processes represented in the dual-route model, based on studies of children with particular subtypes of dyslexia, and on univariate and multivariate genetic modelling of reading performance in the normally reading population.

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The heritability of conscientiousness has been one of the least explored of the NEO PI domains. Here we focus on the facet scales of the conscientiousness domain, estimating both their heritability and their correlations with measures of IQ and academic achievement (Queensland Core Skills Test; QCST) in a sample of adolescent twins and their non-twin siblings. Our findings confirmed positive associations between IQ and the facets of Competence and Dutifulness (ranging 0.11-0.27), with academic achievement showing correlations of 0.27 and 0.15 with these same facets and 0.15 with Deliberation. All conscientiousness facets were influenced by genes (broad sense heritabilities ranging 0.18-0.49) and unique environment, but common environment was judged unimportant. A multivariate genetic analysis including Competence, Dutifulness, IQ (verbal, performance) and QCST scores showed that common variance was primarily explained by a general additive genetic factor (loadings ranging 0.15-0.84). Future multivariate genetic analysis which incorporates Openness to Experience dimensions may improve the interpretation of these findings. (c) 2005 Elsevier Ltd. All rights reserved.

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The relative stability and magnitude of genetic and environmental effects underlying major dimensions of adolescent personality across time were investigated. The Junior Eysenck Personality Questionnaire was administered to over 540 twin pairs at ages 12, 14 and 16 years. Their personality scores were analyzed using genetic simplex modeling which explicitly took into account the longitudinal nature of the data. With the exception of the dimension lie, multivariate model fitting results revealed that familial aggregation was entirely explained by additive genetic effects. Results from simplex model fitting suggest that large proportions of the additive genetic variance observed at ages 14 and 16 years could be explained by genetic effects present at the age of 12 years. There was also evidence for smaller but significant genetic innovations at 14 and 16 years of age for male and female neuroticism, at 14 years for male extraversion, at 14 and 16 years for female psychoticism, and at 14 years for male psychoticism.