Biomedical subjects

Sophia S F Lee

Publications and source records attributed to Sophia S F Lee.

4 recordsLinked to original sources

PubMed2007

Confidence intervals for multinomial logistic regression in sparse data.

Logistic regression is one of the most widely used regression models in practice, but alternatives to conventional maximum likelihood estimation methods may be more appropriate for small or sparse samples. Modification of the logistic regression score function to remove first-order bias is equivalent to penalizing the likelihood by the Jeffreys prior, and yields penalized maximum likelihood estimates (PLEs) that always exist, even in samples in which maximum likelihood estimates (MLEs) are infinite. PLEs are an attractive alternative in small-to-moderate-sized samples, and are preferred to exact conditional MLEs when there are continuous covariates. We present methods to construct confidence intervals (CI) in the penalized multinomial logistic regression model, and compare CI coverage and length for the PLE-based methods to that of conventional MLE-based methods in trinomial logistic regressions with both binary and continuous covariates. Based on simulation studies in sparse data sets, we recommend profile CIs over asymptotic Wald-type intervals for the PLEs in all cases. Furthermore, when finite sample bias and data separation are likely to occur, we prefer PLE profile CIs over MLE methods.

Aspartate Aminotransferases↗

PubMed2005

Resampling methods to reduce the selection bias in genetic effect estimation in genome-wide scans.

Using the simulated data of Problem 2 for Genetic Analysis Workshop 14 (GAW14), we investigated the ability of three bootstrap-based resampling estimators (a shrinkage, an out-of-sample, and a weighted estimator) to reduce the selection bias for genetic effect estimation in genome-wide linkage scans. For the given marker density in the preliminary genome scans (7 cM for microsatellite and 3 cM for SNP), we found that the two sets of markers produce comparable results in terms of power to detect linkage, localization accuracy, and magnitude of test statistic at the peak location. At the locations detected in the scan, application of the three bootstrap-based estimators substantially reduced the upward selection bias in genetic effect estimation for both true and false positives. The relative effectiveness of the estimators depended on the true genetic effect size and the inherent power to detect it. The shrinkage estimator is recommended when the power to detect the disease locus is low. Otherwise, the weighted estimator is recommended.

Chromosome Mapping↗

PubMed2005

Comparison of family-based association tests in chromosome regions selected by linkage-based confidence intervals.

We use the Genetic Analysis Workshop 14 simulated data to explore the effectiveness of a two-stage strategy for mapping complex disease loci consisting of an initial genome scan with confidence interval construction for gene location, followed by fine mapping with family-based tests of association on a dense set of single-nucleotide polymorphisms. We considered four types of intervals: the 1-LOD interval, a basic percentile bootstrap confidence interval based on the position of the maximum Zlr score, and asymptotic and bootstrap confidence intervals based on a generalized estimating equations method. For fine mapping we considered two family-based tests of association: a test based on a likelihood ratio statistic and a transmission-disequilibrium-type test implemented in the software FBAT. In two of the simulation replicates, we found that the bootstrap confidence intervals based on the peak Zlr and the 1-LOD support interval always contained the true disease loci and that the likelihood ratio test provided further strong confirmatory evidence of the presence of disease loci in these regions.

Chromosomes, Human↗

PubMed2005

Reduced visual function associated with infantile spasms in children on vigabatrin therapy.

PURPOSE: To use visual evoked potential (VEP) testing to determine whether visual deficits are present in children with a history of vigabatrin use. METHODS: Contrast sensitivity and visual acuity were assessed by visual evoked potential testing and compared between 28 children (mean age, 4.90 +/- 4.92 years) with seizure disorders who had taken vigabatrin and 14 typically developing children (mean age, 3.14 +/- 1.70 years). Exclusion criteria were heritable eye disease, suspected cortical visual impairment, nystagmus, and prematurity >2 weeks. The effects of the following factors on contrast sensitivity and visual acuity were examined: type of seizure (infantile spasms versus other), ERG result, duration of vigabatrin therapy, cumulative dosage of vigabatrin, and other seizure medications (other versus no other medication). RESULTS: Contrast sensitivity and visual acuity were reduced in vigabatrin-treated children with infantile spasms compared with vigabatrin-treated children with other seizure disorders and typically developing control subjects. The other factors examined had no significant effect on contrast sensitivity or visual acuity, with adjustment for seizure type. CONCLUSIONS: Children with infantile spasms on vigabatrin may have compromised visual function, even in the absence of suspected cortical visual impairment. The children tested in the present study have reduced vision, probably associated with infantile spasms rather than vigabatrin.

Adolescent↗