Simplified formulas for detecting linkage with a quantitative character

A simplified form of Smith's test for linkage between a mendelian and a quantitative character is described. Numerical examples are given of its application to the Kell blood group and sole dermatoglyphics.     

Genome scan of human systemic lupus erythematosus: evidence for linkage on chromosome 1q in African-American pedigrees

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies against intracellular antigens including DNA, ribosomal P, Ro (SS-A), La (SS-B), and the spliceosome. Etiology is suspected to involve genetic and environmental factors. Evidence of genetic involvement includes: associations with HLA-DR3, HLA-DR2, Fcgamma receptors (FcgammaR) IIA and IIIA, and hereditary complement component deficiencies, as well as familial aggregation, monozygotic twin concordance >20%, lambdas > 10, purported linkage at 1q41-42, and inbred mouse strains that consistently develop lupus. We have completed a genome scan in 94 extended multiplex pedigrees by using model-based linkage analysis. Potential [log10 of the odds for linkage (lod) > 2.0] SLE loci have been identified at chromosomes 1q41, 1q23, and 11q14-23 in African-Americans; 14q11, 4p15, 11q25, 2q32, 19q13, 6q26-27, and 12p12-11 in European-Americans; and 1q23, 13q32, 20q13, and 1q31 in all pedigrees combined. An effect for the FcgammaRIIA candidate polymorphism) at 1q23 (lod = 3.37 in African-Americans) is syntenic with linkage in a murine model of lupus. Sib-pair and multipoint nonparametric analyses also support linkage (P < 0.05) at nine loci detected by using two-point lod score analysis (lod > 2.0). Our results are consistent with the presumed complexity of genetic susceptibility to SLE and illustrate racial origin is likely to influence the specific nature of these genetic effects.     

No evidence of linkage between schizophrenia and D3 dopamine receptor gene locus in Icelandic pedigrees

Mice homozygous for the lpr gene develop autoantibodies and polyclonal B cell activation similar to what is seen in human systemic lupus erythematosus patients. We have previously shown that an lpr-specific intrinsic B cell defect was necessary for autoantibody production in this model. In the current study, we have further defined these autoantibody-producing B cells. Two major subsets of B cells have been described. B-1 cells (CD5+ B cells) can be distinguished from conventional B cells on the basis of phenotype, cytokine secretion, gene expression, anatomical location, and function. In addition, B-1 cells have been implicated in autoimmunity in several murine and human studies. To address the question of which B cell subset produces autoantibodies in lpr mice, we used immunoglobulin heavy chain (Igh) allotype-marked peritoneal (B-1 cell source) and bone marrow (conventional B cell source) cells from lpr mice to establish B cell chimeras. We used two general approaches. In one, we reconstituted sublethally irradiated mice with B-1 cells of one allotype and bone marrow cells of another allotype. In the second method, we suppressed endogenous B cells in neonatal mice with allotype-specific anti-IgM antibody, and injected peritoneal cells of another allotype. After antibody treatment was stopped, the mouse's conventional B cells recovered, but the B-1 subset was only reconstituted by the donor. In both types of chimeras, antichromatin, rheumatoid factor, and anti-single stranded DNA (ssDNA) autoantibodies were produced by the conventional B cell bone marrow source. In addition, an age-related decrease in peritoneal B-1 cells was seen, even in unmanipulated lpr mice. These data show that lpr B-1 cells are not important producers of autoantibodies. Conventional B cells are the source of autoantibodies directed at chromatin, ssDNA, and IgG.     

No evidence for significant linkage between bipolar affective disorder and chromosome 18 pericentromeric markers in a large series of multiplex extended pedigrees

Bipolar affective disorder (BP) is a major neuropsychiatric disorder with high heritability and complex inheritance. Previously reported linkage between BP and DNA markers in the pericentromeric region of chromosome 18, with a parent-of-origin effect (linkage was present in pedigrees with paternal transmission and absent in pedigrees with exclusive maternal inheritance), has been a focus of interest in human genetics. We reexamined the evidence in one of the largest samples reported to date (1,013 genotyped individuals in 53 unilineal multiplex pedigrees), using 10 highly polymorphic markers and a range of parametric and nonparametric analyses. There was no evidence for significant linkage between BP and chromosome 18 pericentromeric markers in the sample as a whole, nor was there evidence for significant parent-of-origin effect (pedigrees with paternal transmission were not differentially linked to the implicated chromosomal region). Two-point LOD scores and single-locus sib-pair results gave some support for suggestive linkage, but this was not substantiated by multilocus analysis, and the results were further tempered by multiple test effects. We conclude that there is no compelling evidence for linkage between BP and chromosome 18 pericentromeric markers in this sample.     

Increasing the general practitioner''s role in detecting patients with tuberculosis

A total of 132 patients of both sexes who ranged from 32 to 49 years old were studied in a general hospital setting. They were diagnosed as having developed organic affection of the brain presenting with the leading psychosis-like syndrome, viz, personality and behaviour derangements--[F 07.0] according to the international classification ICD-10. All those having been examined in 1986 took part in the elimination of the effects of the Chernobyl accident. Based on the findings obtained it has been ascertained that late in the course of the organic brain affection sequelae there start prevailing first and foremost elements of affective-volitional disorders transforming the mental make-up of patients according to psychopathy-like type of mentality.     

Multiple cause-of-death data as a tool for detecting artificial trends in the underlying cause statistics: a methodological study

The aims of the study were: (i) to identify trends in the underlying cause-of-death statistics that are due to changes in the coders' selection and coding of causes, and (ii) to identify changes in the coders' documented registration principles that can explain the observed trends in the statistics. 31 Basic Tabulation List categories from the Swedish national cause-of-death register for 1970-1988 were studied. The coders' tendency to register a condition as the underlying cause of death (the underlying cause ratio) was estimated by dividing the occurrence of the condition as underlying cause (the underlying cause rate) with the total registration of the condition (the multiple cause rate). When the development of the underlying cause rate series followed more closely the underlying cause ratio series than the multiple cause rate series, and a corresponding change in the registration rules could be found, the underlying cause rate trend was concluded to be due to changes in the coders' tendency to register the condition. For thirteen categories (fourteen trends), the trends could be explained by changes in the coders' interpretation practice: five upward, four insignificant, and five downward trends. In addition, for three categories the trends could be explained by new explicit ICD-9 rules.     

Anticipation in multiplex schizophrenia pedigrees

The dopamine D4 receptor, recently identified by molecular biological techniques, is expressed in areas of the brain implicated in the pathophysiology of schizophrenia. Although it has a lower affinity than the D2 receptor for most antipsychotic drugs, the D4 receptor has a higher affinity for clozapine, which may explain the unique efficacy of clozapine in the treatment of schizophrenia. However, there is no association between genetic alterations of the D4 gene and either the development of schizophrenia or response to clozapine administration, nor is the absence of the receptor related to major neuropsychiatric deficits. The report of an increase in D4 receptor density in the striatum in schizophrenia has not been consistently confirmed. Thus, it appears that there is little to support the development of D4 antagonists as potential antipsychotic agents.     

Covariate effects on linkage and association using a general pair method

The "general pair method" (GPM) is a nonparametric, identity-by-state (IBS) method of assessing linkage between a chromosomal marker and a binary phenotype. It is applicable to any pedigree structure, and uses marker information from affected as well as unaffected individuals. Results obtained here from nuclear families (Problem 2A) are contrasted with those from extended pedigrees (Problem 2B). Test statistics for chromosomal linkage between each marker and disease status are contrasted with tests for "direct association" which test the hypothesis that a particular allele is associated disease status across all pedigrees. A novel extension of the GPM is presented here for testing whether the strength of linkage (and/or association) depends on the levels of a covariate (i.e., dependency on gender, age, the levels of the "environmental factor," or the levels of the "quantitative phenotypes" supplied). The GPM is seen to have some power to detect major gene 1 on chromosome 5, and major gene 3 on chromosome 4. The gender interaction effects proved too small to detect. No direct associations are found.     

Nonparametric Post Hoc Comparisons for Trend.

Post hoc procedures using orthogonal polynomials are illustrated for 3 nonparametric tests that are frequently employed by behavioral scientists in the analysis of empirical data. These examples involve null hypotheses which have been rejected by the Kruskal-Wallis 1-way analysis-of-variance test for rank data, by the Friedman 2-way analysis-of-variance test for rank data, and by the Cochran extension of the McNemar test of change for dichotomous data. Finally, the proposed post hoc procedures are compared to planned-comparison methods. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

试论统计模型在统计认识中的作用

统计工作是社会经济管理中一项重要的工作.传统的统计方法主要是描述性统计,数据资料主要靠统计报表来搜集整理,所得出的结论往往与实际情况有较大差距.本人通过长期讲授<统计学原理>,深感统计模型在统计工作中的重要作用.应用统计模型,可以提高数据资料应用的可靠性和可行性,从而可以对经济现象的发展前景,做量上的预计和推算,对经济决策、计划管理提供重要的参考依据.     

Statistical Nonparametric Model for Natural Salt Estimation

Many rivers in the Western U.S. suffer from high salinity content due to both natural and human-induced causes. Computer simulation models are often used to estimate future salinity levels and identify mitigation needs. To date, estimation of future natural salt loading has utilized linear relationships between natural flow and natural salt. We develop a nonparametric regression technique to fit a functional relationship between natural flow and natural salt. The main advantages of the nonparametric technique are: (1) No prior assumptions have to be made as to the underlying form of the relationship and (2) any arbitrary relationship (linear or nonlinear) can be modeled. In addition, we develop a resampling scheme to provide confidence intervals of the natural salt estimates from the nonparametric model. We apply this model to data from a stream gauge at Glenwood Springs, Colo., on the Colorado River. We show that the new natural salt model reduces the average overprediction of salt mass shown in the existing natural salt model for the period 1941–1995 by approximately 15% (78,000?metric?tons).     

Mapping genes that underlie ethnic differences in disease risk: methods for detecting linkage in admixed populations, by conditioning on parental admixture

The mechanism by which interleukin-6 (IL-6) protects multiple myeloma (MM) plasma cells from apoptosis induced by anti-fas antibodies and dexamethasone was studied. Anti-apoptotic concentrations of IL-6 had no effect on cell-cycle distribution or activation of RAF-1 or ERK in dexamethasone- or anti-fas-treated 8226 and UCLA #1 MM cell lines. However, IL-6-dependent protection of viability correlated with an inhibition of dexamethasone- and anti-fas-induced activation of jun kinase (JNK) and AP-1 transactivation. To test the hypothesis that cytokine-induced protection was mediated through inhibition of JNK/c-jun, we also inhibited c-jun function in 8226 cells via introduction of a mutant dominant negative c-jun construct. Mutant c-jun-containing MM cells were also resistant to anti-fas-induced apoptosis but were significantly more sensitive to dexamethasone-induced apoptosis. These results support the notion that IL-6 protects MM cells against anti-fas through its inhibitory effects on JNK/c-jun but indicate protection against dexamethasone occurs through separate, yet unknown pathways.     

Evidence for a major gene elevating serum bilirubin concentration in Utah pedigrees

In case-control studies, lower serum bilirubin levels have been associated with increased risk of developing coronary heart disease (CHD). We have also previously shown that serum bilirubin has a significant polygenic component. The purpose of the present investigation was to determine whether there was statistical evidence for a major gene explaining a significant portion of individual variation in serum total bilirubin levels and whether this gene might alter the risk of CHD. Serum bilirubin measurements were obtained from 1240 adults in 84 Utah pedigrees screened twice: from 1980 to 1983 and again from 1983 to 1986. Bivariate maximum-likelihood segregation analysis of serum bilirubin levels obtained from the two clinic visits indicated that a major gene was responsible for elevated levels in 11.5% of the persons in these pedigrees. Phenotypic variations in visit 1 bilirubin arising from polygenes were highly correlated with the phenotypic variation due to polygenes in visit 2 bilirubin, indicating a stable genetic contribution to bilirubin over 2.5 years of follow-up. The major gene explained 27% and 28% of the variance in bilirubin levels at visit 1 and visit 2, respectively. There were no correlations of unmeasured environmental factors influencing bilirubin between the two clinic visits. At both visits, persons with early CHD had lower levels of bilirubin than unaffected persons (P < .01). The odds ratio for the risk of CHD in the high-homozygote group was 0.31, P = .09. We conclude that there is a major gene modestly raising serum bilirubin levels. Since cross-sectional data indicate that low serum bilirubin levels increase the risk of CHD, this major gene may be protective against CHD for about 12% of the persons in this study.     

Parental sex effects in bipolar affective disorder pedigrees

Measurements of transepithelial electrical resistance (TEER), the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) test and monitoring of poly(ethylene glycol) (PEG) transport have been used to study the effects of the non-ionic surfactants Solulan C24 and Solulan 16, either free in solution or as an integral part of niosome bi-layers, on intestinal epithelial cells from man (Caco-2 cell monolayers). The effects on epithelial integrity and on the transport of the hydrophilic drug metformin depend on the concentration of the surfactants. At concentrations above 1% the effect on TEER of the surfactant in niosomal form and free in solution were equivalent whereas cell viability was preserved to a higher concentration of Solulans when the Solulans were present in the niosomal form. It was concluded that the toxic effect of niosomes arises from free surfactant present in the niosome suspension.     

Bayesian Probabilistic Inference for Nonparametric Damage Detection of Structures

This paper presents a Bayesian hypothesis testing-based probabilistic assessment method for nonparametric damage detection of building structures, considering the uncertainties in both experimental results and model prediction. A dynamic fuzzy wavelet neural network method is employed as a nonparametric system identification model to predict the structural responses for damage evaluation. A Bayes factor evaluation metric is derived based on Bayes’ theorem and Gaussian distribution assumption of the difference between the experimental data and model prediction. The metric provides quantitative measure for assessing the accuracy of system identification and the state of global health of structures. The probability density function of the Bayes factor is constructed using the statistics of the difference of response quantities and Monte Carlo simulation technique to address the uncertainties in both experimental data and model prediction. The methodology is investigated with five damage scenarios of a four-story benchmark building. Numerical results demonstrate that the proposed methodology provides an effective approach for quantifying the damage confidence in the structural condition assessment.     

Probabilistic Failure Prediction for Deteriorating Pipelines: Nonparametric Approach

Component failures in water distribution systems are usually predicted by parametric models where the model parameters are determined by projecting the past failure rates of the component to the future. This paper shows that in such techniques, failures are implicitly assumed to be stationary random processes. However, due to the nonstationary nature of some influencing factors, this assumption may lead to inaccurate predictions. A new nonparametric technique is developed for failure prediction of classes of pipes considering this nonstationary process. The presented technique uses limited data that are typical to the databases of water distribution systems. In this method, maximum likelihood estimates of the probability of future failures are calculated and used, both to predict the number of failures occurring within a specified period of time in future, and to provide some lower and upper bounds (confidence intervals) for the estimations. This technique is applied to predict the failures of water pipes in western suburbs of Melbourne. Results of the predictions are compared with the empirical results from a failure record. Deviation of these predictions from empirical measures in terms of both rejection rates and mean-square errors of predictions are acceptable.     

Transformed statistics for use in test construction.

This paper draws together the several formulae which have been developed for determining item-test and/or item-criterion statistics which utilize highly efficient grouping. Grouping transformations have been found to be relatively efficient and precise enough for general use. Departures from normality because of grouping transformations are not extreme enough to invalidate results. (PsycINFO Database Record (c) 2010 APA, all rights reserved)