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At least 343 records · Page 19Linked to original sources
PubMed2004

The intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism is not associated with ischaemic heart disease: an investigation using family-based tests of association.

The possible role of the K469E polymorphism in the intercellular adhesion molecule-1 (ICAM-1) gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population using two recently described family-based tests of association. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped for the ICAM-1 K469E polymorphism. Using the combined transmission disequilibrium test (TDT)/sib-TDT and the pedigree disequilibrium test (PDT), no association between the ICAM-1 K469E polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the ICAM-1 K469E polymorphism is not associated with IHD.

Adult↗
PubMed2001

Family-based tests of association and/or linkage.

The large literature on family-based tests of association and/or linkage is reviewed, concentrating on the underlying principles and on recent methodological developments. We explain the distinction between testing for association and testing for linkage, and give our views on the circumstances in which each is the appropriate null hypothesis.

Alleles↗
PubMed2004

Dorsolateral prefrontal cortex involvement in memory post-retrieval monitoring revealed in both item and associative recognition tests.

Post-retrieval monitoring is a process that contributes to episodic memory retrieval by allowing people to evaluate the relevance of retrieved information in relation to the task requirements. Previous studies have suggested that post-retrieval monitoring is supported by the dorsolateral prefrontal cortex (DLPFC). In this study, we used functional magnetic resonance imaging (fMRI) to evaluate involvement of the DLPFC in post-retrieval monitoring in two different recognition tests (item recognition and associative recognition). The item recognition memory test required subjects to make old/new judgments and the associative recognition memory test required them to make intact/rearranged judgments. Because the post-retrieval monitoring demand increases during old (hits) relative to new (correct rejections) item recognition trials, and also during rearranged (correct rejections) relative to intact (hits) associative recognition trials, we evaluated the brain activation associated with the interaction of Memory test (item versus associative) by Recognition trial (hit versus correct rejection). As expected, the DLPFC was activated in this interaction as well as for both old relative to new item recognition trials and rearranged relative to intact associative recognition trials. This study provides strong evidence that DLPFC activation supports post-retrieval monitoring across different types of recognition tasks.

Adult↗
PubMed2000

Comparison of tests for association and linkage in incomplete families.

To analyze incomplete families, the following statistical tests can be used: LRAT-a simple likelihood-based association test, TRANSMIT, SIBASSOC/STDT, and RCTDT. We compared these four tests, for the diallelic case, on simulated data sets. The comparisons focused on the power to detect linkage and association when different familial structures, resistance to population stratification, resistance to misclassification of the disease status of the healthy sib, and the effect of nonpaternity were considered. The simulations lead to the following conclusions. The type I errors of TRANSMIT, SIBASSOC/STDT, and RCTDT were not affected by population stratification. LRAT showed bias under strong population stratification. High nonpaternity rates can lead to inflated type I errors, highlighting the importance of identification of half sibs. Under different homogeneous models, the power of TRANSMIT was very similar to that of LRAT, and, similarly, no difference in power was observed between SIBASSOC/STDT and RCTDT. Under various recessive and additive models, TRANSMIT was slightly more powerful than SIBASSOC/STDT when monoparental families with one affected and one unaffected sib were analyzed. Under various dominant models, SIBASSOC/STDT was slightly more powerful than TRANSMIT. Misclassification of the disease status of healthy sibs, as well as the discarding of incomplete families, resulted in a consistent loss of power.

Adult↗
PubMed2007

Power calculations for likelihood ratio tests for offspring genotype risks, maternal effects, and parent-of-origin (POO) effects in the presence of missing parental genotypes when unaffected siblings are available.

Genotype-based likelihood-ratio tests (LRT) of association that examine maternal and parent-of-origin effects have been previously developed in the framework of log-linear and conditional logistic regression models. In the situation where parental genotypes are missing, the expectation-maximization (EM) algorithm has been incorporated in the log-linear approach to allow incomplete triads to contribute to the LRT. We present an extension to this model which we call the Combined_LRT that incorporates additional information from the genotypes of unaffected siblings to improve assignment of incompletely typed families to mating type categories, thereby improving inference of missing parental data. Using simulations involving a realistic array of family structures, we demonstrate the validity of the Combined_LRT under the null hypothesis of no association and provide power comparisons under varying levels of missing data and using sibling genotype data. We demonstrate the improved power of the Combined_LRT compared with the family-based association test (FBAT), another widely used association test. Lastly, we apply the Combined_LRT to a candidate gene analysis in Autism families, some of which have missing parental genotypes. We conclude that the proposed log-linear model will be an important tool for future candidate gene studies, for many complex diseases where unaffected siblings can often be ascertained and where epigenetic factors such as imprinting may play a role in disease etiology.

Algorithms↗
PubMed2001

[Prognostic value of cardiac perfusion scintigraphy associated with the dobutamine test in acute coronary syndromes].

OBJECTIVES: This study aimed to establish the value of myocardial ischemia induced by the dobutamine infusion test associated to 99m technetium isonitrile single photon emission computed tomography in patients with unstable angina or non Q-wave infarction during the first days in the Coronary Care Unit. METHODS: Fifty three patients with unstable coronary syndromes and common medical treatment were studied with a moderate-dose dobutamine test (5 to 20 microgram/Kg/min) using a 99mTc-MIBI SPECT. The results were correlated with the incidence of recurrent angina, infarction, death or revascularization. RESULTS: The dobutamine test induced a reversible perfusion defect in 36 patients (68%) and angina in 12 of them (12/36, 33%). However, the patients who had a positive test had a similar incidence of events as those with a negative test (58% vs 59%). Thus, while the sensitivity of the dobutamine test to identify patients at risk was relatively high (68%), its specificity (32%) and its negative predictive value (41%) were low. The patients with dobutamine-induced angina, however, had a higher scintigraphy score (3.0 +/- 1,7 vs 1.6 +/- 1.8, p < 0.02) and a higher incidence of recurrent angina (8/12, 67% vs 13/41, 31%, p < 0.04) than those without, at a comparable double product. CONCLUSIONS: In conventionally treated patients with unstable coronary syndromes, the specificity of the inducible scintigraphic ischemia with moderate dose of dobutamine performed during the first days is too low to be used as a marker for in-hospital events. However, inducible angina with dobutamine suggests an extensive jeopardized area and/or a particularly reduced ischemic threshold.

Adrenergic beta-Agonists↗
PubMed2002

On a general class of conditional tests for family-based association studies in genetics: the asymptotic distribution, the conditional power, and optimality considerations.

Family-based association tests (FBATs) provide simple and powerful tests to detect association between a genetic marker and a disease-susceptibility locus, manifest in subjects by a phenotype or disease trait. Here we propose a new class of conditional tests for family-based association studies that includes most of the established tests and their generalizations. The class of tests is very general; it can be applied to longitudinal and multivariate traits or phenotypes, multiple genetic markers, and many other situations not yet discussed in the literature. For any test in this class, we derive the asymptotic distribution under the null hypothesis, the conditional power under any alternative hypothesis, and the optimal offset for single degree of freedom tests. The proposed methodology is illustrated with a genetic study of asthma.

Asthma↗
PubMed2001

Test of association for quantitative traits in general pedigrees: the quantitative pedigree disequilibrium test.

Many statistical methods have been proposed in recent years to test for genetic linkage and association between genetic markers and traits of interest through unrelated nuclear families. However, most of these methods are not valid tests of association in the presence of linkage when some of the nuclear families are related. As a result, related nuclear families in large pedigrees cannot be included in a single analysis to test for linkage disequilibrium. Recently, Martin et al. [Am J Hum Genet 67:146-54, 2000] proposed the pedigree disequilibrium test (PDT) to test for linkage and association in general pedigrees for qualitative traits. In this article, we develop a similar quantitative pedigree disequilibrium test (QPDT) to test for linkage and association in general pedigrees for quantitative traits. We apply both the PDT and the QPDT to analyze the sequence data from the seven candidate genes in the simulated data sets in the Genetic Analysis Workshop 12.

Chromosome Mapping↗
PubMed1978

A nonparametric test for association with censored data.

A nonparametric procedure is proposed for the problem of testing association between two continuous variables when one is subject to arbitrary censoring. The motivation for the procedure derives from our finding that Cox's likelihood procedure may not adequately control the size of the test. The proposed procedure allows the censoring mechanism to depend on the independent variable, is simple computationally, and provides accurate control over the size of the test even for quite small samples. Asymptotic results suggest that it may provide a sensitive alternative to Cox's procedure. An example dealing with survival following operation for myasthenia gravis is provided, wherein a method for testing after adjustment for covariate information is described.

Humans↗
PubMed2006

The admixture maximum likelihood test: a novel experiment-wise test of association between disease and multiple SNPs.

Disease association studies often test large numbers of markers, and various methods have been proposed to correct for multiple testing. In this paper, we propose an admixture maximum likelihood approach that estimates both the proportion of associated single nucleotide polymorphisms (SNPs) and their typical effect size. We assessed this method and compared it with several previously proposed approaches by simulation. The maximum likelihood approach performed similarly to or better than all other tests across a wide range of alternative hypotheses. The rank truncated product method also had good power, though somewhat inferior to the maximum likelihood approach in most cases. A simple Bonferroni correction performed best only when the number of associated SNPs was small.

Genetic Predisposition to Disease↗
PubMed1993

Positive antiglobulin test in association with sulindac: involvement of the Rh factor.

We investigated the development of a positive direct antiglobulin test associated with the use of the nonsteroid anti-inflammatory drug sulindac. The drug was shown to be the cause of the positive direct antiglobulin test using red cells treated in vitro with solutions of native sulindac and its two major metabolites. Serum from the patient contained sulindac-dependent red cell antibodies which could not be demonstrated when red cells having the Rh phenotype D-- were employed in the test procedure. An eluate prepared from the patients' red cells reacted against untreated red cells having common Rh phenotypes, but not against target red cells with the Rh phenotypes D-- or Rh null. The eluate showed stronger reactivity against the cells having common Rh phenotypes when they were treated with solutions of a metabolite of sulindac, but failed to react against treated red cells having the Rh phenotype D-- or Rh null. The results of our investigations point to an interaction between sulindac and/or its metabolites and Rh structures on the red cell membrane as the initial step in the production of drug dependent and autoantibodies leading to the positive direct antiglobulin test.

Coombs Test↗
PubMed2006

Improved association analyses of disease subtypes in case-parent triads.

The sampling of case-parent triads is an appealing strategy for conducting association analyses of complex diseases. In certain situations, one may have interest in using the triads to identify genetic variants that are associated with a specific subtype of disease, perhaps related to a characteristic cluster of symptoms. A straightforward strategy for conducting such a subtype analysis would be to analyze only those triads with the subtype of interest. While such a strategy is valid, we show that triads without the subtype of interest can provide additional genetic information that increases power to detect association with the subtype of interest. We incorporate this additional information using a likelihood-based framework that permits flexible modeling and estimation of allelic effects on disease subtypes and also allows for missing parental data. Using simulated data under a variety of genetic models, we show that our proposed association test consistently outperforms association tests that only analyze triads with the subtype of interest. We also apply our method to a triad study of attention-deficit hyperactivity disorder and identify a genetic variant in the dopamine transporter gene that is associated with a subtype characterized by extreme levels of both inattentive and hyperactive-impulsive symptoms.

Attention Deficit and Disruptive Behavior Disorder↗
PubMed2006

Validity, efficiency, and robustness of a family-based test of association.

We propose a new test of linkage in the presence of allelic association that uses all available information in a sample of nuclear families, including parental phenotypes, genotypes from both affected and unaffected siblings, and families with homozygous parents. The test is based on the conditional framework developed by Rabinowitz and Laird [2000: Hum Hered 50:211-223] and is thus immune to population stratification and can be applied to families with any pattern of missing information. The test statistic is a conditional likelihood ratio based on a standard two-point linkage model with allelic association, where parameters are estimated from the sample. Through a simulation study, we determined that the proposed test has near optimal power for a wide range of scenarios, outperforming FBAT both when data were complete and when parental genotypes were missing, although differences between the two tests diminish as the genetic effect is reduced. To assess robustness, we also evaluated the performance of the tests under scenarios with population stratification and found that although there is a loss of efficiency, our proposed test remains a strong competitor to FBAT.

Alleles↗
PubMed2004

[Aging and schizophrenia: the relation of age to clinical symptoms and cognitive functions in schizophrenia].

OBJECTIVE: The course of clinical symptoms and cognitive functions with aging in schizophrenia is still unclear. The aim of this study was to investigate the effects of age on psychopathological symptoms and cognitive functions in schizophrenia. METHOD: Forty-one patients with schizophrenia and 22 healthy subjects as a control group were included in the study. The relation of age to the severity of the symptoms and the cognitive functions were investigated in patients with schizophrenia. The age related variations in cognitive functions among patients and healthy subjects were analyzed by separating each group into young (18-34 years) and older (35-60 years) age groups. RESULTS: There was a negative correlation between age and positive scores of the Positive and Negative Syndrome Scale. Age was negatively correlated to the Digit Span Test in patients with schizophrenia and the Rey Verbal Learning and Memory Test and Controlled Word Association Test in healthy subjects. There was a significant age related difference between the two groups in the Controlled Word Association Test. CONCLUSION: The results of this study revealed that age had an influence on attention but not on any other domains in patients with schizophrenia, and on verbal learning-memory and verbal fluency in the control group. This might show a cognitive impairment that does not significantly change with aging in schizophrenia. This study also demonstrated an improvement in positive symptoms with aging.

Adolescent↗
PubMed2000

Circumventing multiple testing: a multilocus Monte Carlo approach to testing for association.

Advances in marker technology have made a dense marker map a reality. If each marker is considered separately, and separate tests for association with a disease gene are performed, then multiple testing becomes an issue. A common solution uses a Bonferroni correction to account for multiple tests performed. However, with dense marker maps, neighboring markers are tightly linked and may have associated alleles; thus tests at nearby marker loci may not be independent. When alleles at different marker loci are associated, the Bonferroni correction may lead to a conservative test, and hence a power loss. As an alternative, for tests of association that use family data, we propose a Monte Carlo procedure that provides a global assessment of significance. We examine the case of tightly linked markers with varying amounts of association between them. Using computer simulations, we study a family-based test for association (the transmission/disequilibrium test), and compare its power when either the Bonferroni or Monte Carlo procedure is used to determine significance. Our results show that when the alleles at different marker loci are not associated, using either procedure results in tests with similar power. However, when alleles at linked markers are associated, the test using the Monte Carlo procedure is more powerful than the test using the Bonferroni procedure. This proposed Monte Carlo procedure can be applied whenever it is suspected that markers examined have high amounts of association, or as a general approach to ensure appropriate significance levels and optimal power.

Alleles↗
PubMed1991

Comparison of the amnesic effects of midazolam and diazepam.

Thirty patients undergoing gastroscopy received intravenous premedication with either midazolam or diazepam in a randomised double blind study. Mean dosages were similar for the midazolam (6.13 mg) and diazepam (6.4 mg) groups. Neuropsychological testing pre- and post-medication comprised the Wechsler Memory Scale, Complex Figure Test, Word Association Test, and a Tactile Memory Test. There was a significant impairment on post-medication tests requiring delayed recall of verbal, visual and tactile stimuli. Midazolam produced significantly greater anterograde amnesia than diazepam at similar mean dosages. With the exception of Digit Span and Associate Learning, cognitive tasks which do not require delayed recall were not affected. It is concluded that the amnesic deficit is discrete and not secondary to sedative effects.

Amnesia↗
PubMed2005

Linkage analysis and association analysis in the presence of linkage using age at onset of COGA alcoholism data.

Complex disease mapping usually involves a combination of linkage and association techniques. Linkage analysis can scan the entire genome in a few hundred tests. Association tests may involve an even greater number of tests. However, association tests can localize the susceptibility genes more accurately. Using a recently developed combined linkage and association strategy, we analyzed a subset of the Collaborative Study on the Genetics of Alcoholism (COGA) data for the Genetic Analysis Workshop 14 (GAW14). In this analysis, we first employed linkage analysis based on frailty models that take into account age of onset information to establish which regions along the chromosome are likely to harbor disease susceptibility genes for alcohol dependence. Second, we used an association analysis by exploiting linkage disequilibrium to narrow down the peak regions. We also compare the methods with mean identity-by-descent tests and transmission/disequilibrium tests that do not use age of onset information.

Age of Onset↗
PubMedDate not supplied

Variability associated with testing shelled corn for fumonisin.

Variances associated with sampling, sample preparation, and analytical steps of a test procedure that measures fumonisin in shelled corn were estimated. The variance associated with each step of the test procedure increases with fumonisin concentration. Functional relationships between variance and fumonisin concentration were estimated by regression analysis. For each variance component, functional relationships were independent of fumonisin type (total, B1, B2, and B3 fumonisins). At 2 ppm, coefficients of variation associated with sampling (1.1 kg sample), sample preparation (Romer mill and 25 g subsample), and analysis are 16.6, 9.1, and 9.7%, respectively. The coefficient of variation associated with the total fumonisin test procedure was 45% and is about the same order of magnitude as that for measuring aflatoxin in shelled corn with a similar test procedure.

Carboxylic Acids↗