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Effects of lateralized cerebral dysfunction on the Continuous Paired-Associate Test.

Some authorities have advocated matching tests on several critical psychometric properties before inferring the presence of a differential pattern of deficit. This study examined the effects of lateralized cerebral dysfunction on the matched Verbal and Design subtests of the Continuous Paired-Associate Test (CPAT). Patients with lateralized destructive lesions were studied in Experiment 1. Epileptic patients with lateralized electroencephalographic findings were studied in Experiment 2. Left but not right hemispheric abnormalities impaired performance on the Verbal CPAT, but only for destructive lesions. The Designs CPAT was a nonspecific indicator of cerebral dysfunction. For studies with the goal of predicting laterality of cerebral dysfunction, we advocate a two-step strategy of test development. The first step would make use of the principle of double dissociation in selecting items to compose subtests. The second step would involve an item analysis of subtests to determine the need for matching.

Adolescent↗

Testing association between candidate-gene markers and phenotype in related individuals, by use of estimating equations.

Association studies are one of the major strategies for identifying genetic factors underlying complex traits. In samples of related individuals, conventional statistical procedures are not valid for testing association, and maximum likelihood (ML) methods have to be used, but they are computationally demanding and are not necessarily robust to violations of their assumptions. Estimating equations (EE) offer an alternative to ML methods, for estimating association parameters in correlated data. We studied through simulations the behavior of EE in a large range of practical situations, including samples of nuclear families of varying sizes and mixtures of related and unrelated individuals. For a quantitative phenotype, the power of the EE test was comparable to that of a conventional ML test and close to the power expected in a sample of unrelated individuals. For a binary phenotype, the power of the EE test decreased with the degree of clustering, as did the power of the ML test. This result might be partly explained by a modeling of the correlations between responses that is less efficient than that in the quantitative case. In small samples (< 50 families), the variance of the EE association parameter tended to be underestimated, leading to an inflation of the type I error. The heterogeneity of cluster size induced a slight loss of efficiency of the EE estimator, by comparison with balanced samples. The major advantages of the EE technique are its computational simplicity and its great flexibility, easily allowing investigation of gene-gene and gene-environment interactions. It constitutes a powerful tool for testing genotype-phenotype association in related individuals.

Female↗

Genotype-based association test for general pedigrees: the genotype-PDT.

Many family-based tests of linkage disequilibrium (LD) are based on counts of alleles rather than genotypes. However, allele-based tests may not detect interactions among alleles at a single locus that are apparent when examining associations with genotypes. Family-based tests of LD based on genotypes have been developed, but they are typically valid as tests of association only in families with a single affected individual. To take advantage of families with multiple affected individuals, we propose the genotype-pedigree disequilibrium test (geno-PDT) to test for LD between marker locus genotypes and disease. Unlike previous tests for genotypic association, the geno-PDT is valid in general pedigrees. Simulations to compare the power of the allele-based PDT and geno-PDT reveal that under an additive model, the allele-based PDT is more powerful, but that the geno-PDT can have greater power when the genetic model is recessive or dominant. Perhaps the most important property of the geno-PDT is the ability to test for association with particular genotypes, which can reveal underlying patterns of association at the genotypic level. These genotype-specific tests can be used to suggest possible underlying genetic models that are consistent with the pattern of genotypic association. This is illustrated through an application to a candidate gene analysis of the MLLT3 gene in families with Alzheimer disease. The geno-PDT approach for testing genotypes in general family data provides a useful tool for identifying genes in complex disease, and partitioning individual genotype contributions will help to dissect the influence of genotype on risk.

Alzheimer Disease↗

A threat in the computer: the race implicit association test as a stereotype threat experience.

Three experiments test whether the threat of appearing racist leads White participants to perform worse on the race Implicit Association Test (IAT) and whether self-affirmation can protect from this threat. Experiments 1 and 2 suggest that White participants show a stereotype threat effect when completing the race IAT, leading to stronger pro-White scores when the test is believed to be diagnostic of racism. This effect increases for domain-identified (highly motivated to control prejudice) participants (Experiment 2). In Experiment 3, self-affirmation inoculates participants against stereotype threat while taking the race IAT. These findings have methodological implications for use of the race IAT and theoretical implications concerning the malleability of automatic prejudice and the potential interpersonal effects of the fear of appearing racist.

Adult↗

Predictors of success on the Canadian Nurses Association testing service (CNATS) examination.

This retrospective study examined the relationship of selected admissions variables and in-course performance to success in the Canadian Nurses Association Testing Service (CNATS) examinations of 114 students admitted directly from secondary school to a four-year integrated, problem-based learning (PBL) baccalaureate nursing program in Canada. Data were analyzed using two separate hierarchical stepwise regression equations. The first equation examined a set of secondary school grades (Ontario Academic Credits, or OACs) used to calculate university admission averages and their ability to predict CNATS performance. OAC English was found to be the best predictor, followed by OAC chemistry and the admission average obtained on other OAC subjects. The second regression equation looked at in-course grades as potential predictors of CNATS scores. The basic sciences variable proved to be the best predictor, followed by research methodology, first-year Nursing Concepts I, a problem-based nursing average, and a clinical practice average. Findings support the continued use of English and chemistry as admission criteria. The basic sciences courses and first-year nursing courses also emerged as statistically significant predictors of licensure examination success.

Canada↗

[Word association test in myocardial infarct].

The distinguishing feature of associative reactions of patients with myocardial infarction is the marked predominance of egocentric response and the lesser variance of the reactions to critical verbal stimuli. As compared to patients with myocardial infarction and normal psychic condition and to healthy individuals, patients with psychopathological changes due to myocardial infarction gave disordered associative answers to emotionally meaningful verbal stimuli significantly more frequently and with a more marked affective coloration. These signs may serve in different diagnosis in appraising the psychic status of patients with myocardial infarction.

Adult↗

Power of QTL detection using association tests with family controls.

The power of testing for a population-wide association between a biallelic quantitative trait locus and a linked biallelic marker locus is predicted both empirically and deterministically for several tests. The tests were based on the analysis of variance (ANOVA) and on a number of transmission disequilibrium tests (TDT). Deterministic power predictions made use of family information, and were functions of population parameters including linkage disequilibrium, allele frequencies, and recombination rate. Deterministic power predictions were very close to the empirical power from simulations in all scenarios considered in this study. The different TDTs had very similar power, intermediate between one-way and nested ANOVAs. One-way ANOVA was the only test that was not robust against spurious disequilibrium. Our general framework for predicting power deterministically can be used to predict power in other association tests. Deterministic power calculations are a powerful tool for researchers to plan and evaluate experiments and obviate the need for elaborate simulation studies.

Analysis of Variance↗

Measuring alcohol expectancies with the implicit association test.

Researchers have relied primarily on self-report questionnaires to measure alcohol expectancies. These questionnaires assess explicit expectancies about alcohol but donot provide any measure of the implicit processes that might also play an important role in determining drinking. The implicit association test (IAT; A. G. Greenwald, D. E. McGhee, & L. K. Schwartz, 1998), a reaction time task, measures differential associations of 2 target concepts with an attribute. In this study, the IAT provided a measure of the strength of associations of alcohol concepts to positive or negative outcomes in memory. This implicit measure of alcohol expectancies successfully predicted alcohol use in 103 undergraduates. The findings also supported the hypothesis that an implicit measure of expectancy can add to the predictive power of existing questionnaire-based measures.

Adult↗

The association between psychological distance and construal level: evidence from an implicit association test.

According to construal level theory (N. Liberman, Y. Trope, & E. Stephan, in press; Y. Trope & N. Liberman, 2003), people use a more abstract, high construal level when judging, perceiving, and predicting more psychologically distal targets, and they judge more abstract targets as being more psychologically distal. The present research demonstrated that associations between more distance and higher level of construal also exist on a pure conceptual level. Eight experiments used the Implicit Association Test (IAT; A. G. Greenwald, D. E. McGhee, & J. L. K. Schwartz, 1998) to demonstrate an association between words related to construal level (low vs. high) and words related to four dimensions of distance (proximal vs. distal): temporal distance, spatial distance, social distance, and hypotheticality. In addition to demonstrating an association between level of construal and psychological distance, these findings also corroborate the assumption that all 4 dimensions of psychological distance are related to level of construal in a similar way and support the notion that they all are forms of psychological distance.

Concept Formation↗

Association testing in 9,000 people fails to confirm the association of the insulin receptor substrate-1 G972R polymorphism with type 2 diabetes.

The insulin receptor substrate (IRS)-1 is an important component of the insulin signal transduction cascade. Several reports suggest that a Gly-->Arg change in codon 972 is associated with type 2 diabetes and related traits, and a recent meta-analysis reported a modest but nominally significant association with type 2 diabetes (odds ratio [OR] 1.25 in favor of carriers of the Arg allele [95% CI 1.05-1.48). To test the reproducibility of the model in a recent meta-analysis, we examined genotype-phenotype correlation in three large Caucasian samples (not previously reported for this variant) totaling 9,000 individuals (estimated to have >95% power to obtain a P < 0.05 for the OR of 1.25 estimated in the meta-analysis). In our combined sample, comprising 4,279 case and 3,532 control subjects, as well as 1,189 siblings discordant for type 2 diabetes, G972R was not associated with type 2 diabetes (OR 0.96 [0.84-1.10], P = 0.60). Genotype at G972R had no significant effect on various measures of insulin secretion or insulin resistance in a set of Scandinavian samples in whom we had detailed phenotypic data. In contrast, the well-documented associations of peroxisome proliferator-activated receptor gamma P12A and Kir6.2 E23K with type 2 diabetes are both robustly observed in these 9,000 subjects, including an additional (previously unpublished) confirmation of Kir6.2 E23K and type 2 diabetes in the Polish and North American samples (combined OR 1.15 [1.05-1.26], P = 0.001). Despite genotyping 9,000 people and >95% power to reproduce the estimated OR from the recent meta-analysis, we were unable to replicate the association of the IRS-1 G972R polymorphism with type 2 diabetes.

Amino Acid Substitution↗

The defensive function of persecutory delusions: an investigation using the Implicit Association Test.

INTRODUCTION: Bentall and colleagues (Bentall & Kaney, 1996; Kinderman & Bentall, 1996, 1997) claim that persecutory delusions are constructed defensively, for the maintenance of self-esteem. A central prediction of their model is that such delusions will be associated with discrepancies between overt and covert self-esteem. METHODS: The present study employed a new methodology that has been widely used in investigations of implicit attitudes, the Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998), to assess covert self-esteem and to test the above prediction. Overt self-esteem was assessed using the Rosenberg Self-Esteem Scale and an adjective self-relevance ratings measure. These measures were administered to 10 patients with acute persecutory delusions, 10 patients with remitted persecutory delusions, and 19 healthy control participants. RESULTS: Patients with persecutory delusions were found to have lower covert self-esteem (as assessed using the IAT) than healthy controls and patients with remitted persecutory delusions. On two measures of overt self-esteem, however, the persecutory deluded group did not differ significantly from the other groups once the effects of comorbid depression had been taken into account. CONCLUSIONS: These results are thus consistent with a model of persecutory delusions as serving the defensive function of maintaining self-esteem.

Adult↗

[Different responses in word association tests in normotensive and hypertensive subjects].

Activation of latent associations by word stimuli of different emotional relevance as well as the accompanying electrophysiological tracings reveal statistically significantly characteristics in juvenile essential (arterial) hypertensives as compared to normotensives. This applies to the verbal reactions as well as to the electrophysical concomitants. Under additional cognitive demands both groups achieve better performance. This rise is significantly greater, however for hypertensives than for normotensives. Our special recording system permitted exact phonographic registration of the verbal stimulus and reaction as well as of the PGR.

Galvanic Skin Response↗

Regional admixture mapping and structured association testing: conceptual unification and an extensible general linear model.

Individual genetic admixture estimates, determined both across the genome and at specific genomic regions, have been proposed for use in identifying specific genomic regions harboring loci influencing phenotypes in regional admixture mapping (RAM). Estimates of individual ancestry can be used in structured association tests (SAT) to reduce confounding induced by various forms of population substructure. Although presented as two distinct approaches, we provide a conceptual framework in which both RAM and SAT are special cases of a more general linear model. We clarify which variables are sufficient to condition upon in order to prevent spurious associations and also provide a simple closed form "semiparametric" method of evaluating the reliability of individual admixture estimates. An estimate of the reliability of individual admixture estimates is required to make an inherent errors-in-variables problem tractable. Casting RAM and SAT methods as a general linear model offers enormous flexibility enabling application to a rich set of phenotypes, populations, covariates, and situations, including interaction terms and multilocus models. This approach should allow far wider use of RAM and SAT, often using standard software, in addressing admixture as either a confounder of association studies or a tool for finding loci influencing complex phenotypes in species as diverse as plants, humans, and nonhuman animals.

Computer Simulation↗

Family-based association tests suggest linkage between surfactant protein B (SP-B) (and flanking region) and respiratory distress syndrome (RDS): SP-B haplotypes and alleles from SP-B-linked loci are risk factors for RDS.

Genetic variants of surfactant protein B (SP-B) have been associated with respiratory distress syndrome (RDS) in the prematurely born infant. We wished to determine linkage between RDS and SP-B single nucleotide polymorphisms (SNPs) [-18 (A/C), 1013 (A/C), 1580 (C/T), and 9306 (A/G)] or SP-B-linked microsatellite [(D2S388, D2S2232, (AAGG)n, and GATA41E01 (or D2S1331)] loci and identify susceptibility or protective alleles and haplotypes. We genotyped 132 families consisting of one or two parents and at least one child affected with RDS and performed biallelic and multiallelic family-based association test (FBAT) analysis, and extended transmission disequilibrium test (ETDT). ETDT analysis identified the microsatellite SP-B-linked loci (except D2S2232) to be linked to RDS. One allele from each of these three marker loci contributes to the risk of RDS. Multiallelic FBAT analysis detected a signal of linkage for the region of the four SNP loci. Three haplotypes within this region contribute to RDS risk. Although no other region showed significant linkage as judged by multiallelic FBAT, biallelic FBAT analysis revealed three potential susceptibility haplotypes formed by two to four loci within the SP-B and SP-B-linked microsatellite region. Each haplotype included GATA41E01, which was identified by ETDT analysis to be linked to RDS. We conclude that SP-B or SP-B-linked loci are linked to RDS and certain alleles or haplotypes are susceptibility or protective factors for the development of RDS in infants born prematurely.

Adult↗

Association tests of interleukin-6 (IL-6) and type II tumor necrosis factor receptor (TNFR2) genes with bone mineral density in Caucasians using a re-sampling approach.

Interleukin 6 (IL-6) and tumor necrosis factor (TNF) are important cytokines for bone turnover. In this study, a promoter C-174G single-nucleotide polymorphism (SNP) within the IL-6 gene affecting the transcription rate of IL-6 and an exon 6 T676G SNP of the TNF receptor 2 (TNFR2) gene causing an M196R amino-acid change were examined for their relationship with bone mineral density (BMD). Four hundred and five multi-offspring Caucasian families, including 389 male children and 744 female children, were used. One thousand re-samplings were conducted and in each data set, one child was randomly chosen from each family. For each data set, one-way analysis of variance (ANOVA) test was independently implemented using age, age2, sex, height and weight as covariates. There were 523, 288, 204 and 369 significant results out of 1,000-replicate re-samplings of the data of the IL-6 SNP (P<0.05) for one-third, mid-distal, ultradistal radius BMD, and the first principal component (PC1) extracted from the three radial BMDs, respectively, which means that the confidences for associations of the C-174G SNP in the IL-6 gene with one-third, mid-distal, ultradistal radius (totally called distal forearm) BMDs, and PC1, were 52.3, 28.8, 20.4 and 36.9%, respectively. For this SNP with BMD at other skeletal sites and the TNFR2 T676G SNP with BMD at any site, significant results were far less than 200 times out of 1,000 re-sampling replicates. The exceedingly consistent permutation results further improved the confidence of the associations. It may imply that the IL-6 C-174G SNP is associated with distal forearm BMD, but there is no evidence that the TNFR2 T676G SNP is related with BMD in US Caucasians. This is the first attempt to conduct association test utilizing a re-sampling approach. Our results may be more informative than other association analyses that were only based on one sampling result. The results also suggest that different samplings could produce significantly diverse results even for the same population and the results from one sampling are unlikely to be conclusive. Our results have significant implications for association studies and interpretation of non-reproducible association findings.

Body Weights and Measures↗

A review of the special tests associated with shoulder examination. Part I: the rotator cuff tests.

Careful examination of the shoulder is an essential component in forming a diagnosis of problems in this area. A number of tests have been described that are claimed to improve diagnostic accuracy by specifically examining one component of the shoulder complex. Many of these tests are eponymous, and there is confusion about not only how to perform them but also what conclusion to draw from the results. This article attempts to clarify the tests used to examine the rotator cuff by presenting them as described by the original authors with the additional aim of providing a source for those wishing to refresh their knowledge without the need to refer to the original source material.

Humans↗

Effects of scopolamine on delayed-matching-to-sample and paired associates tests of visual memory and learning in human subjects: comparison with diazepam and implications for dementia.

Two experiments examined dose-related effects of 200, 400 and 600 micrograms scopolamine (n = 24, s.c.) and 5 and 10 mg diazepam (n = 6, PO) on parallel tests of visual memory and learning taken from the CANTAB battery. Scopolamine significantly impaired accuracy of performance on a delayed matching to sample test of visual recognition memory in a dose- and delay-dependent manner, but had only marginal decremental effects on a test of visuospatial paired associates learning. Scopolamine significantly lengthened decision times in a visual search matching to sample task at the 400 and 600 micrograms doses, without significantly affecting accuracy. The drug also impaired performance on tests of spatial (on accuracy and response time measures) and pattern (on response time only) memory. Most of the deleterious effects on scopolamine were removed by covariance analyses with indices of subjective sedation, but the effects of delayed matching accuracy and latency remained. By contrast, diazepam significantly impaired paired associates learning but affected delayed matching to sample in a delay-independent manner. These results suggest that scopolamine can produce selective deficits in tests of short-term visual recognition memory which do not depend on overall impairments in arousal and which contrast with deficits in visual associative learning produced by diazepam. They have implications for the pharmacological modelling of dementia and memory disorders in man and for the neurochemical substrates of the short-term recognition memory and associative learning for visual stimuli.

Adult↗