Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “statistical inference”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,099 records · Page 61Linked to original sources
PubMed1986

Molecular genetics of apolipoproteins and coronary heart disease.

A variety of DNA markers for apolipoprotein genes were examined among patients with angiocardiographically proven heart disease and among a variety of normal individuals with various lipid values. An increased frequency of an apoAI-CIII SstI RFLP and an apoB minisatellite (allele 5) was found among patients with CHD. Higher levels of cholesterol were found among carriers of the rare apoB TaqI and the common apoCII TaqI variants, whereas higher levels of triglycerides were found in carriers of the common apoAII MspI and the rare apoB XbaI variants. Lower levels of HDL were found among carriers of the common apoAII MspI and the rare apoB PvuII variants. The biological significance of these results and those of other investigators for the pathogenesis of CHD and hyperlipidemia is suggestive but not yet fully clarified. Additional genetic epidemiologic studies and family investigations will be required. Currently used statistical methodology may lead to false inferences regarding the genetic equilibrium or disequilibrium status of closely linked DNA variants. Conclusions regarding the presence of genetic equilibrium if closely linked flanking markers are in disequilibrium may be faulty.

Alleles↗
PubMed2004

Microsatellite marker data suggest sex-biased dispersal in the common frog Rana temporaria.

Despite being important models in ecological, evolutionary and conservation biology research, very little is known about the dispersal in anuran amphibians, and juvenile dispersal in particular. Using microsatellite data, we assessed signatures of sex-biased migration in the common frog (Rana temporaria) in Scandinavia. Significant heterozygosity deficiency (FIS) and lower assignment value (mAIc) among females suggest that dispersal in R. temporaria is female biased. Also variance of assignment (vAIc), estimated separately for the two sexes, was consistent with this inference, although the difference was not statistically significant. Possible proximate and ultimate explanations for female-biased dispersal in amphibians are discussed.

Animals↗
PubMed2006

A population-based latent variable approach for association mapping of quantitative trait loci.

A population-based latent variable approach is proposed for association mapping of quantitative trait loci (QTL), using multiple closely linked genetic markers within a small candidate region in the genome. By incorporating QTL as latent variables into a penetrance model, the QTL are flexible to characterize either alleles at putative trait loci or potential risk haplotypes/sub-haplotypes of the markers. Under a general likelihood framework, we develop an EM-based algorithm to estimate genetic effects of the QTL and haplotype frequencies of the QTL and markers jointly. Closed form solutions derived in the maximization step of the EM procedure for updating the joint haplotype frequencies of QTL and markers can effectively reduce the computational intensity. Various association measures between QTL and markers can then be derived from the haplotype frequencies of markers and used to infer QTL positions. The likelihood ratio statistic also provides a joint test for association between a quantitative trait and marker genotypes without requiring adjustment for the multiple testing. Extensive simulation studies are performed to evaluate the approach.

Algorithms↗
PubMedDate not supplied

Bayesian communication: a clinically significant paradigm for electronic publication.

OBJECTIVE: To develop a model for Bayesian communication to enable readers to make reported data more relevant by including their prior knowledge and values. BACKGROUND: To change their practice, clinicians need good evidence, yet they also need to make new technology applicable to their local knowledge and circumstances. Availability of the Web has the potential for greatly affecting the scientific communication process between research and clinician. Going beyond format changes and hyperlinking, Bayesian communication enables readers to make reported data more relevant by including their prior knowledge and values. This paper addresses the needs and implications for Bayesian communication. FORMULATION: Literature review and development of specifications from readers', authors', publishers', and computers' perspectives consistent with formal requirements for Bayesian reasoning. RESULTS: Seventeen specifications were developed, which included eight for readers (express prior knowledge, view effect size and variability, express threshold, make inferences, view explanation, evaluate study and statistical quality, synthesize multiple studies, and view prior beliefs of the community), three for authors (protect the author's investment, publish enough information, make authoring easy), three for publishers (limit liability, scale up, and establish a business model), and two for computers (incorporate into reading process, use familiar interface metaphors). A sample client-only prototype is available at http://omie.med.jhmi.edu/bayes. CONCLUSION: Bayesian communication has formal justification consistent with the needs of readers and can best be implemented in an online environment. Much research must be done to establish whether the formalism and the reality of readers' needs can meet.

Bayes Theorem↗
PubMed2003

Adverse pregnancy outcomes around incinerators and crematoriums in Cumbria, north west England, 1956-93.

STUDY OBJECTIVE: To investigate the risk of stillbirth, neonatal death, and lethal congenital anomaly among babies of mothers living close to incinerators and crematoriums in Cumbria, north west England, 1956-93. DESIGN: Retrospective cohort study. Logistic regression was used to investigate the risk of each outcome in relation to proximity at birth to incinerators and crematoriums, adjusting for social class, year of birth, birth order, and multiple births. Continuous odds ratios for trend with proximity to sites were estimated. SETTING: All 3234 stillbirths, 2663 neonatal deaths, and 1569 lethal congenital anomalies among the 244 758 births to mothers living in Cumbria, 1956-1993. MAIN RESULTS: After adjustment for social class, year of birth, birth order, and multiple births, there was an increased risk of lethal congenital anomaly, in particular spina bifida (odds ratio 1.17, 95% CI: 1.07 to 1.28) and heart defects (odds ratio 1.12, 95% CI: 1.03 to 1.22) around incinerators and an increased risk of stillbirth (odds ratio 1.04, 95% CI: 1.01 to 1.07) and anencephalus (odds ratio 1.05, 95% CI: 1.00 to 1.10) around crematoriums. CONCLUSIONS: The authors cannot infer a causal effect from the statistical associations reported in this study. However, as there are few published studies with which to compare our results, the risk of spina bifida, heart defects, stillbirth, and anencephalus in relation to proximity to incinerators and crematoriums should be investigated further, in particular because of the increased use of incineration as a method of waste disposal.

Congenital Abnormalities↗
PubMed1982

An association study of Huntington's disease and HLA.

HLA antigens were determined in a sample of 47 patients with the diagnosis and family history of Huntington's disease (HD). Two groups consisting of 20 and 11 unrelated patients respectively were investigated. In the first group an increased frequency of HLA-Bw44 (p less than 0.05) and of HLA-A11 (p less than 0.05) was found, but after correcting for multiple inferences the differences were no longer statistically significant. No correlation was found between sex, age of onset, initial symptom, and HLA type. In order to find out if the increased frequency of HLA-Bw44 was real or due to chance, the second group of patients was investigated. In this group the frequency of HLA-Bw44 did not differ from the normal population and a strong association between HLA and HD could be excluded.

Female↗
PubMed2004

Advances in blind source separation (BSS) and independent component analysis (ICA) for nonlinear mixtures.

In this paper, we review recent advances in blind source separation (BSS) and independent component analysis (ICA) for nonlinear mixing models. After a general introduction to BSS and ICA, we discuss in more detail uniqueness and separability issues, presenting some new results. A fundamental difficulty in the nonlinear BSS problem and even more so in the nonlinear ICA problem is that they provide non-unique solutions without extra constraints, which are often implemented by using a suitable regularization. In this paper, we explore two possible approaches. The first one is based on structural constraints. Especially, post-nonlinear mixtures are an important special case, where a nonlinearity is applied to linear mixtures. For such mixtures, the ambiguities are essentially the same as for the linear ICA or BSS problems. The second approach uses Bayesian inference methods for estimating the best statistical parameters, under almost unconstrained models in which priors can be easily added. In the later part of this paper, various separation techniques proposed for post-nonlinear mixtures and general nonlinear mixtures are reviewed.

Bayes Theorem↗
PubMed1983

Conducting state and local health needs assessments. Designs and strategies.

A comprehensive set of five needs assessment techniques designed to facilitate informed decisions about mental health services planning at the state or local level are presented. These include: (1) estimating the size of the target population based on statistical extrapolations from prevalence rates or inferences from indirect indicators; (2) surveys of institution-based populations; (3) surveys of service providers; (4) client-targeted surveys; and (5) surveys of key informants. Each technique is discussed in terms of its unique design considerations, strengths and weaknesses, the phase's association with its application, and estimated resource requirements. Mental health needs assessments can be conducted in a cost-effective manner, especially important in an era when rational decisions about the allocation of scarce resources are essential.

Data Collection↗
PubMed2005

A genome-wide scanning and fine mapping study of COGA data.

A thorough genetic mapping study was performed to identify predisposing genes for alcoholism dependence using the Collaborative Study on the Genetics of Alcoholism (COGA) data. The procedure comprised whole-genome linkage and confirmation analyses, single locus and haplotype fine mapping analyses, and gene x environment haplotype regression. Stratified analysis was considered to reduce the ethnic heterogeneity and simultaneously family-based and case-control study designs were applied to detect potential genetic signals. By using different methods and markers, we found high linkage signals at D1S225 (253.7 cM), D1S547 (279.2 cM), D2S1356 (64.6 cM), and D7S2846 (56.8 cM) with nonparametric linkage scores of 3.92, 4.10, 4.44, and 3.55, respectively. We also conducted haplotype and odds ratio analyses, where the response was the dichotomous status of alcohol dependence, explanatory variables were the inferred individual haplotypes and the three statistically significant covariates were age, gender, and max drink (the maximum number of drinks consumed in a 24-hr period). The final model identified important AD-related haplotypes within a candidate region of NRXN1 at 2p21 and a few others in the inter-gene regions. The relative magnitude of risks to the identified risky/protective haplotypes was elucidated.

Alcoholism↗
PubMed2006

Differentiation among populations with migration, mutation, and drift: implications for genetic inference.

Populations may become differentiated from one another as a result of genetic drift. The amounts and patterns of differentiation at neutral loci are determined by local population sizes, migration rates among populations, and mutation rates. We provide exact analytical expressions for the mean, variance, and covariance of a stochastic model for hierarchically structured populations subject to migration, mutation, and drift. In addition to the expected correlation in allele frequencies among populations in the same geographic region, we demonstrate that there is a substantial correlation in allele frequencies among regions at the top level of the hierarchy. We propose a hierarchical Bayesian model for inference of Wright's F-statistics in a two-level hierarchy in which we estimate the among-region correlation in allele frequencies by substituting replication across loci for replication across time. We illustrate the approach through an analysis of human microsatellite data, and we show that approaches ignoring the among-region correlation in allele frequencies underestimate the amount of genetic differentiation among major geographic population groups by approximately 30%. Finally, we discuss the implications of these results for the use and interpretation of F-statistics in evolutionary studies.

Animal Migration↗
PubMed1982

The inheritance of sinking-pre-beta lipoprotein and its relation to the Lp(a) antigen.

We have investigated the genetics of plasma sinking-pre-beta lipoprotein (sp beta) as determined by the method of Breckenridge and Maguire, using several approaches: (i) a population study, (ii) a twin study and (iii) the use of family data. In addition, by the use of split samples, the sp beta level as determined by us was correlated with Lp(a) typing carried out in Oslo by Dr. Kåre Berg. Although the sp beta level is a continuous character, the results clearly showed it to be to a considerable extent under the control of the major autosomal gene pair constituted by the alleles Lpa and Lp, which mainly control the production of the Lp(a) antigen, Lpa being dominant. In our data the boundary between the LpLp and LpaLp genotypes appeared to fall between the sp beta 2 and 3 mg% levels, while that between LpaLp and LpaLpa was in the 15 mg% region. These boundaries, which were inferred from both typing and population statistics, received good confirmation from the family data. It appears that some 88% of the variation in sp beta level is directly ascribed to segregation of Lpa and Lp. On the basis of the twin study and other data, we conclude that the residual observed variation in sp beta is almost entirely ascribed to analytical error of determination and polygenic effects, the influence of environment being negligible. The heritability is close to 100%.

Antigens↗
PubMed2004

Statistical and conceptual issues in defining post-operative cognitive dysfunction.

The occurrence of post-operative cognitive dysfunction is a distressing complication following surgery. In an effort to gain a more complete understanding of patients' cognitive recovery following surgical procedures common neuropsychological assessment tools have been adopted in a repeated measures design. It is widely regarded that this represents the most comprehensive method of determining cognitive status in this population but it has resulted in a number of statistical and conceptual difficulties in attempting to infer significant change. The current paper outlines these core difficulties and provides some potential methods to overcome these.

Cognition Disorders↗
PubMed1991

A Monte Carlo method for Bayesian inference in frailty models.

Many analyses in epidemiological and prognostic studies and in studies of event history data require methods that allow for unobserved covariates or "frailties." Clayton and Cuzick (1985, Journal of the Royal Statistical Society, Series A 148, 82-117) proposed a generalization of the proportional hazards model that implemented such random effects, but the proof of the asymptotic properties of the method remains elusive, and practical experience suggests that the likelihoods may be markedly nonquadratic. This paper sets out a Bayesian representation of the model in the spirit of Kalbfleisch (1978, Journal of the Royal Statistical Society, Series B 40, 214-221) and discusses inference using Monte Carlo methods.

Algorithms↗
PubMed2003

Comparison of fuzzy inference, logistic regression, and classification trees (CART). Prediction of cervical lymph node metastasis in carcinoma of the tongue.

OBJECTIVES: In this paper three statistical methods [logistic regression, classification and regression tree (CART), and fuzzy inference] for the prediction of lymph node metastasis in carcinoma of the tongue are compared. METHODS: A retrospective collection of data in 75 patients treated for tongue cancer was carried out at the Clinic and Policlinic for Oral and Maxillo-facial Surgery at the University Hospital of Freiburg in Germany between January 1990 and December 1999; biopsy material was used for laboratory evaluations. Statistical methods for the prediction of lymph node metastasis were compared using ROC curves and accuracy rates. RESULTS: All three methods show similar results for the prediction of lymph node metastasis with slightly superior results for fuzzy inference and CART. A great overlap is apparent in the ROC curves. The best result observed for fuzzy inference and CART was a sensitivity of 79.2% [95% confidence interval: (57.8%; 92.9%)] and a specificity of 86.3% (73.7%; 94.3%); the best result for predictions based on the logistic regression was a sensitivity of 66.7% (44.7%; 84.4%) and a specificity of 80.4% (66.9%; 90.2%). Accuracy rates of fuzzy method and CART were higher [accuracy rate for fuzzy method and CART: 84% (73.7%; 91.4%), for logistic regression method: 73.3%, 95%-CI: (61.9%; 82.9%)]. CONCLUSIONS: From a clinical point of view, the predictive ability of the three methods is not sufficiently large to justify use of these methods in daily practice. Other factors probably on the molecular level are needed for the prediction of lymph node metastasis.

Decision Support Techniques↗
PubMed2004

Structure and evolution of protein interaction networks: a statistical model for link dynamics and gene duplications.

BACKGROUND: The structure of molecular networks derives from dynamical processes on evolutionary time scales. For protein interaction networks, global statistical features of their structure can now be inferred consistently from several large-throughput datasets. Understanding the underlying evolutionary dynamics is crucial for discerning random parts of the network from biologically important properties shaped by natural selection. RESULTS: We present a detailed statistical analysis of the protein interactions in Saccharomyces cerevisiae based on several large-throughput datasets. Protein pairs resulting from gene duplications are used as tracers into the evolutionary past of the network. From this analysis, we infer rate estimates for two key evolutionary processes shaping the network: (i) gene duplications and (ii) gain and loss of interactions through mutations in existing proteins, which are referred to as link dynamics. Importantly, the link dynamics is asymmetric, i.e., the evolutionary steps are mutations in just one of the binding parters. The link turnover is shown to be much faster than gene duplications. Both processes are assembled into an empirically grounded, quantitative model for the evolution of protein interaction networks. CONCLUSIONS: According to this model, the link dynamics is the dominant evolutionary force shaping the statistical structure of the network, while the slower gene duplication dynamics mainly affects its size. Specifically, the model predicts (i) a broad distribution of the connectivities (i.e., the number of binding partners of a protein) and (ii) correlations between the connectivities of interacting proteins, a specific consequence of the asymmetry of the link dynamics. Both features have been observed in the protein interaction network of S. cerevisiae.

Biological Evolution↗
PubMed2006

Unstable inferences? An examination of complex survey sample design adjustments using the Current Population Survey for health services research.

Statistical analysis of the Current Population Survey's Annual Social and Economic Supplement is used widely in health services research. However, the statistical evidence cited from the Current Population Survey (CPS) is not always consistent because researchers use a variety of methods to produce standard errors that are fundamental to significance tests. This analysis examines the 2002 Annual Social and Economic Supplement's (ASEC) estimates of national and state average income, national and state poverty rates, and national and state health insurance coverage rates. Findings show that the standard error estimates derived from the public use CPS data perform poorly compared with the survey design-based estimates derived from restricted internal data, and that the generalized variance parameters currently used by the U.S. Census Bureau in its ASEC reports and funding formula inputs perform erratically. Because the majority of published research (both by academics and Census Bureau analysts) does not make use of the survey design-based information available only on the internal ASEC data file, we argue that the Census Bureau ought to use alternative methods for its official ASEC reports. We also argue that for public use data the Census Bureau should produce a set of replicate weights for the ASEC or release a set of sample design variables that incorporate statistical "noise" to maintain respondent confidentiality (e.g., pseudo-primary sampling units) as other federal government surveys do. This is essential to make appropriate inferences using the ASEC data regarding statistical significance and estimate variance for health policy analysis.

Censuses↗
PubMed2000

A new statistic for the analysis of association between trait and polymorphic marker loci.

Inference for detecting the existence of an association between a diallelic marker and a trait locus is based on the chi-squared statistic with one degree of freedom. For polymorphic markers with m alleles (2), three approaches are mainly used in practice. First, one may use Pearson's chi-squared statistic with m-1 degrees of freedom (d.f.) but this leads to a loss in test power. Second, one can select an allele to be the most associated and then collapse the other allele categories into a single class. This reduces in a biased way, the locus to a diallelic system. Third, one may use the Terwilliger [J.D. Terwilliger, Am. J. Hum. Genet. 56 (1995) 777] likelihood ratio statistic which has a non-standard unknown limiting probability distribution. In this paper, we propose a new statistic, L(D), based on the second testing approach. We derive the asymptotic probability distribution of L(D) in an easy way. Simulation studies show that L(D) is more powerful than Pearson's chi-squared statistic with m-1 d.f.

Alleles↗
PubMed2004

Should we be worried about long-branch attraction in real data sets? Investigations using metazoan 18S rDNA.

Although long-branch attraction (LBA) is frequently cited as the cause of anomalous phylogenetic groupings, few examples of LBA involving real sequence data are known. We have found several cases of probable LBA by analyzing subsamples from an alignment of 18S rDNA sequences for 133 metazoans. In one example, maximum parsimony analysis of sequences from two rotifers, a ctenophore, and a polychaete annelid resulted in strong support for a tree grouping two "long-branch taxa" (a rotifer and the ctenophore). Maximum-likelihood analysis of the same sequences yielded strong support for a more biologically reasonable "rotifer monophyly" tree. Attempts to break up long branches for problematic subsamples through increased taxon sampling reduced, but did not eliminate, LBA problems. Exhaustive analyses of all quartets for a subset of 50 sequences were performed in order to compare the performance of maximum likelihood, equal-weights parsimony, and two additional variants of parsimony; these methods do differ substantially in their rates of failure to recover trees consistent with well established, but highly unresolved phylogenies. Power analyses using simulations suggest that some incorrect inferences by maximum parsimony are due to statistical inconsistency and that when estimates of central branch lengths for certain quartets are very low, maximum-likelihood analyses have difficulty recovering accepted phylogenies even with large amounts of data. These examples demonstrate that LBA problems can occur in real data sets, and they provide an opportunity to investigate causes of incorrect inferences.

Animals↗