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Results for “association testing”

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PubMed1996

Efficacy and side-effects of clozapine: testing for association with allelic variation in the dopamine D4 receptor gene.

Genetic factors are supposed to play a major role not only in the etiology of psychiatric disorders but also in individual response to medications. To test the hypothesis that inter-individual differences in response to clozapine and the occurrence of side-effects might be influenced by variations in the dopamine D4 receptor gene, we examined frequencies of four known polymorphic sites affecting protein structure in the dopamine D4 receptor gene in 149 patients with schizophrenia or schizoaffective disorder treated with clozapine. The D4 polymorphisms included a 13-base pair deletion, which through a frameshift leads to a truncated nonfunctional receptor protein. There were, however, no significant differences in genotype counts between responders and nonresponders. Furthermore, no side-effect was found to be associated with genetic variants of the dopamine D4 receptor.

Adult↗
PubMed1999

Monitoring the dissemination of an educational protocol on pediatric asthma in family practice: a test of associations between dissemination variables.

Many asthma education programs aim at reducing morbidity. Now that effective programs are available, the next step is the nationwide dissemination to achieve morbidity reduction. A dissemination of a tested program has been undertaken in Dutch primary care, guided by the Diffusion of Innovation theory. It was hypothesized that greater awareness and concern and/or receptivity about asthma self-management would make it more likely that family physicians would adopt the program. Family physicians were considered more likely to adopt the program if they saw it as an improvement on their current way of providing education, as easy to use, and as having observable outcomes. It was expected that once the program had been adopted, and as it was being implemented, it would increasingly be perceived by its users as successful. Finally, more perceived success of performance was expected to be related to continued use. Both longitudinal and cross-sectional data largely confirmed the hypotheses.

Adult↗
PubMed1994

The distribution of Q: a powerful sibship test of association.

Non-random inheritance of the two parental haplotypes among siblings affected by certain diseases has long been used to provide evidence of the presence of disease susceptibility genes. The distribution of a powerful test, called Q, based on haplotype concordance and discordance, is derived under the null hypothesis of random inheritance of haplotypes by affected siblings. The presence of a disease gene possibly linked to one of the haplotypes causes a change in the distribution of these haplotypes in the affected siblings. This distribution is found to be that of the sum of two independent variates contributed by the two parents in all parental types except one where both parents are heterozygous for the disease allele; which is dealt with separately. For comparison, the tables showing the powers of the test along with those of another well-known test, the N-test of haplotype concordance, are given. This is because Q is a modification of N to deal with the case when information on unaffected siblings is also available.

Genetic Diseases, Inborn↗
PubMed2004

Efficient computation of significance levels for multiple associations in large studies of correlated data, including genomewide association studies.

Large exploratory studies, including candidate-gene-association testing, genomewide linkage-disequilibrium scans, and array-expression experiments, are becoming increasingly common. A serious problem for such studies is that statistical power is compromised by the need to control the false-positive rate for a large family of tests. Because multiple true associations are anticipated, methods have been proposed that combine evidence from the most significant tests, as a more powerful alternative to individually adjusted tests. The practical application of these methods is currently limited by a reliance on permutation testing to account for the correlated nature of single-nucleotide polymorphism (SNP)-association data. On a genomewide scale, this is both very time-consuming and impractical for repeated explorations with standard marker panels. Here, we alleviate these problems by fitting analytic distributions to the empirical distribution of combined evidence. We fit extreme-value distributions for fixed lengths of combined evidence and a beta distribution for the most significant length. An initial phase of permutation sampling is required to fit these distributions, but it can be completed more quickly than a simple permutation test and need be done only once for each panel of tests, after which the fitted parameters give a reusable calibration of the panel. Our approach is also a more efficient alternative to a standard permutation test. We demonstrate the accuracy of our approach and compare its efficiency with that of permutation tests on genomewide SNP data released by the International HapMap Consortium. The estimation of analytic distributions for combined evidence will allow these powerful methods to be applied more widely in large exploratory studies.

Association↗
PubMed1999

No evidence for an involvement of alleles of polymorphisms in the serotonin1Dbeta and 7 receptor genes in obesity, underweight or anorexia nervosa.

The serotonergic (5-hydroxytryptamine, 5-HT) system has been implicated in body weight regulation and in the etiology of anorexia nervosa (AN). Here we describe the screening of the known Phe-124-Cys polymorphism in the 5-HT1Dbeta receptor gene and of the known Pro-279-Leu polymorphism in the 5-HT7 receptor gene. For association tests allele frequencies were compared between up to 393 extremely obese children and adolescents, 142 underweight students and 84 patients with AN. None of the association tests revealed nominal P-values below 0.3. We conclude that a major role of the investigated polymorphisms in body weight regulation or AN appears unlikely.

Adolescent↗
PubMed1998

A pilot study testing the association between N-acetyltransferases 1 and 2 and risk of oral squamous cell carcinoma in Japanese people.

Risk of oral cancer has been associated with exposure to tobacco smoke, alcohol and with genetic predisposition. The aromatic amines and their metabolites, a class of carcinogens present in tobacco smoke, undergo metabolism (activation or detoxification) through an N- or O-acetylation pathway by the polymorphic enzymes, N-acetyltransferases (NAT)1 or NAT2. The genes that encode these enzymes, NAT1 and NAT2, have a variety of high and low activity alleles and we analyzed these genetic polymorphisms in 62 oral squamous cell carcinoma cases, and 122 healthy control subjects from Japan. NAT1 alleles tested were NAT1*3 (C1095A), NAT1*4 (functional reference allele), NAT1*10 (T1088A,C1095A), NAT1*11(9 bp deletion), NAT1*14 (G560A), NAT1*15 (C559T) and NAT1*17 (C190T). No low activity alleles (NAT1*14, NAT1*15 and NAT1*17) were observed in these Japanese subjects. We observed significantly increased risk [odds ratio 3.72; 95% confidence interval (CI) 1.56-8.90; P < 0.01] associated with the NAT1*10 allele, an allele that contains a variant polyadenylation signal. Stratifying by smoking status we found odds ratios of 5.9 (95% CI 1.13-30.6; P < 0.05) for non-smokers with the NAT1*10 allele and 3.1 (95% CI 1.09-9.07; P < 0.05) for smokers, but these risks were not significantly different from each other. Thus, we did not observe that NAT1*10 alleles confer differential risk among smokers and non-smokers. NAT2 rapid acetylation genotype was not a significant risk factor for oral cancer in this Japanese study population. This is the first study to test for oral cancer risk associated with polymorphism in the NAT1 and NAT2 genes, and these positive findings in our pilot study, while based on small numbers, suggest that the NAT1*10 allele may be a genetic determinant of oral squamous cell carcinoma among Japanese people.

Acetylation↗
PubMed2004

Endothelial nitric oxide synthase gene polymorphism and ischemic heart disease.

BACKGROUND: Ischemic heart disease (IHD), the leading cause of death worldwide, is a multifactorial disease arising from the complex interplay of genetic and environmental factors. There is considerable evidence that nitric oxide (NO) plays an important role in protecting against atherosclerosis, the process underlying IHD. Endothelial NO is synthesized from the amino acid l-arginine by the endothelial isoform of NO synthase (eNOS). Thus, polymorphisms of the eNOS gene, by altering production of NO within the vascular endothelium, are potential risk factors for IHD. Several groups have investigated the role of the G894T polymorphism of the eNOS gene in IHD by using case-control association studies; however, its role is unclear because of contradictory results from these studies. We applied family-based association tests to investigate the role of this polymorphism in IHD in a well-defined Irish population. METHODS: A total of 1023 individuals from 388 families (discordant sibships and parent-offspring trios) were recruited. Linkage disequilibrium between the polymorphism and IHD was tested for by using the combined transmission disequilibrium test/sib-transmission disequilibrium test and pedigree disequilibrium test. RESULTS: Both the combined transmission disequilibrium test/sib-transmission disequilibrium test and pedigree disequilibrium test analyses found no statistically significant excess transmission of either allele to affected individuals (P = .57 and P = .38, respectively). CONCLUSIONS: Using robust family-based association tests specifically designed for the study of complex diseases, we found no evidence that the G894T polymorphism of the eNOS gene has a significant role in the development of IHD in our population.

Female↗
PubMed2001

The Loiano-Monghidoro population-based study of Helicobacter pylori infection: prevalence by 13C-urea breath test and associated factors.

OBJECTIVES: As part of a cross-sectional study on cholelithiasis, 1533 out of 1840 residents in Loiano/Monghidoro, a rural area in Northern Italy (792 men, 741 women, age range 28-80 years), agreed to be further evaluated in relation to their Helicobacter pylori status. METHODS: Each participant performed a 13C-urea breath test (13C-UBT) and provided information on sociodemographic, lifestyle and clinical characteristics. RESULTS: The 13C-UBT was positive in 1041 subjects (67.9%; men: 69%; women: 67%) and was positively associated with increasing age (P < 0.001), alcohol consumption (P < 0.01), a higher number of siblings (P < 0.001) and a personal history of peptic ulcer (P < 0.01), but inversely with a nonmanual occupation (P < 0.001). Overall, H. pylori infection was unrelated to smoking, house pets, and a family history of gastroduodenal diseases. The prevalence of H. pylori infection was 72% in subjects reporting one or more dyspeptic symptoms and 65% among asymptomatic participants (P < 0.001); a multivariate analysis showed that only epigastric pain was significantly, although weakly, associated with 13C-UBT positivity. CONCLUSIONS: This large population-based study showed a prevalence of H. pylori infection higher than that reported by serologic surveys in urban areas. Current H. pylori infection was strongly associated with indicators of lower socioeconomic status, alcohol consumption and increasing age. A role of H. pylori infection in determining epigastric pain was suggested.

Adult↗
PubMed2006

Part-list cuing of associative chains: tests of strategy disruption.

Three experiments assess the veracity of the strategy disruption explanation of part-list cuing impairment. Experiment 1 demonstrated no mnemonic detriment in recall as a result of significant disruption of the participants' self-selected forward associative seriation retrieval strategy. Experiment 2 replicated Experiment 1 while reducing overall performance levels in an attempt to reveal any possible detrimental effects. Experiment 3 ruled out 2 possible alternative explanations by demonstrating the typical part-list cuing impairment within this experimental context. It is concluded that the results challenge a strict version of the strategy disruption hypothesis.

Association Learning↗
PubMed2003

Investigation of the C242T polymorphism of NAD(P)H oxidase p22 phox gene and ischaemic heart disease using family-based association methods.

Ischaemic heart disease is a complex phenotype arising from the interaction of genetic and environmental factors. Excessive production of reactive oxygen species leading to endothelial dysfunction is believed to be important in the pathogenesis of ischaemic heart disease. The NAD(P)H oxidase system generates superoxide anions in vascular cells; however, the role of the C242T polymorphism of the NAD(P)H oxidase p22 phox gene in ischaemic heart disease is unclear due to contradictory results from case-control studies. Consequently, we applied family-based association tests to investigate the role of this polymorphism in ischaemic heart disease in a well-defined Irish population. A total of 1023 individuals from 388 families (discordant sibships and parent/child trios) were recruited. Linkage disequilibrium between the polymorphism and ischaemic heart disease was tested using the combined transmission disequilibrium test (TDT)/sib-TDT (cTDT) and pedigree disequilibrium test (PDT). Both cTDT and PDT analyses found no statistically significant excess transmission of either allele to affected individuals (P =0.30 and P =0.28, respectively). Using robust family-based association tests specifically designed for the study of complex diseases, we found no evidence that the C242T polymorphism of the p22 phox gene has a significant role in the development of ischaemic heart disease in our population.

Adult↗
PubMed1997

Effect of Neospora caninum infection on milk production in first-lactation dairy cows.

OBJECTIVE: To determine whether cows seropositive to Neospora caninum produced less milk during their first lactation than seronegative cows. DESIGN: Repeated-measures, prospective study. ANIMALS: 372 Holstein cows in their first lactation. PROCEDURE: Cows were tested repeatedly before and during their first lactation for antibodies to N caninum. One-way and repeated-measures ANOVA were used to determine whether mean daily milk weights and milk weights from Dairy Herd Improvement Association testing were less for seropositive cows than for seronegative cows. RESULTS: Weekly mean daily milk weights for the 118 seropositive cows were significantly less than those for the 254 seronegative cows, and milk production for seropositive cows (mean, 55.2 lb/cow/d) was 2.5 lb/cow/d less than that for seronegative cows (mean, 57.7 lb/cow/d). Analysis of results from Dairy Herd Improvement Association testing revealed that production of seropositive cows was less for milk (3.1 lb/cow/d), fat-corrected milk (3.6 lb/cow/d), and fat (0.14 lb/cow/d) than production of seronegative cows. CLINICAL IMPLICATIONS: The economic impact of N caninum infection in dairy cows can include reduced revenues from decreased milk production, which may warrant culling of young, seropositive replacement stock.

Analysis of Variance↗
PubMed2005

Grouping local orientation and direction signals to extract spatial contours: empirical tests of "association field" models of contour integration.

Over the last decade or so a great deal of psychophysical research has attempted to delineate the principles by which local orientations and motions are combined across space to facilitate the detection of simple spatial contours. This has led to the development of "association field" models of contour detection which suggest that the strength of linking between neighbouring elements in an image, is determined by the degree to which they aligned along smooth (first-order) curves. To test this assumption we used a path detection paradigm to compare the ability of observers to identify the presence of contours defined by either spatial orientation, motion direction or by specific combinations of both types of visual attribute. The relative alignment of the local orientations and/or directions with respect to the axis of the depicted contour was systematically varied. For orientation-defined contours detection was best when the elements were aligned along (parallel with) the contour axis, approached chance levels for obliquely oriented elements and then improved for elements that were orthogonal to the contour axis (i.e., performance was a U-shaped function of degree of orientation misalignment). This pattern of results was found for both straight and curved contours and is not readily explicable in terms of current association field theories. For motion-defined contours, however, performance simply deteriorated as the relative directions of the constituent path elements were progressively misaligned with respect to the contour. Thus the rules by which local orientations are linked to define spatial contours are qualitatively different from those used for linking local directions and each may be mediated by distinct visual mechanisms. When both orientation and motion cues were simultaneously available, contour detection performance was generally enhanced, in a manner that is consistent with probability summation. We suggest that association field models of orientation linking may need to be extended in light of the present findings.

Cues↗