Biomedical subjects

Shelley Bull

Publications and source records attributed to Shelley Bull.

5 recordsLinked to original sources

PubMed2004

Tests for covariate-associated heterogeneity in IBD allele sharing of affected relatives.

Linkage studies that aim to map susceptibility genes for complex diseases commonly test for excess allele sharing among affected relatives. Conventional methods based on identical-by-descent IBD allele sharing do not allow for possible differences among families, such as arise in the case of locus heterogeneity, and thus have reduced ability to detect linkage in the presence of such heterogeneity. We investigated two approaches to test for heterogeneity in allele sharing, using a family-level covariate that may be associated with different disease mechanisms leading to differences in allele sharing. Likelihood ratio tests for heterogeneity were formulated based on an extension of the linear and exponential likelihood models developed by Kong and Cox. Alternatively, we examined the asymptotic and permutation distributions of T-tests for differences between mean allele-sharing linkage scores from two covariate-defined family subgroups, assuming exchangeability. The size and power of heterogeneity tests were evaluated for S(all) and S(pairs) allele-sharing scoring functions using data sets of families with affected sibling and cousin pairs, generated under a model of locus heterogeneity. In certain simulation scenarios, the likelihood ratio test statistics did not follow the expected asymptotic distributions. The type I error estimates for the T-statistics conformed to nominal 5 and 1% levels in all scenarios considered, and corresponding power was comparable to that of the likelihood ratio tests. Application of these tests for heterogeneity detected significant differences in allele sharing between subgroups of families with inflammatory bowel disease.

Algorithms↗

PubMed2003

Multilevel modeling for the analysis of longitudinal blood pressure data in the Framingham Heart Study pedigrees.

BACKGROUND: The data arising from a longitudinal familial study have a complex correlation structure that cannot be modeled using classical methods for the analysis of familial data at a single time point. METHODS: To fit the longitudinal systolic blood pressure (SBP) pedigree data arising from the Framingham Heart Study, we proposed to use multilevel modeling. That approach was used to distinguish multiple levels of information with individual repeated measurements (Level 1) being made within individuals (Level 2), and individuals clustered within pedigrees (Level 3). Residuals from the subject-specific and pedigree-specific regression models were summed both for the mean SBP and slope of SBP change over time, in order to define two new outcomes that were then used in a genome-wide linkage analysis. RESULTS: Evidence for linkage for the two outcomes (mean SBP and slope) was found in several chromosomal regions with a maximum LOD score of 3.6 on chromosome 8 and 3.5 on chromosome 17 for the mean SBP, and 2.5 on chromosome 1 for SBP slope. However, the linkage on chromosome 8 was only detected when the sample was restricted to subjects between age 25 and 75 and with at least four exams (Cohort 1) or 3 exams (Cohort 2). DISCUSSION: Multilevel modeling is a powerful approach to detect genes involved in complex traits when longitudinal data are available. It allows for complex hierarchical data structure to be taken into account and therefore, a better partitioning of random within-individual variation from other sources of variability (genetic or nongenetic).

Adult↗

PubMed2003

Longitudinal data analysis in pedigree studies.

Longitudinal family studies provide a valuable resource for investigating genetic and environmental factors that influence long-term averages and changes over time in a complex trait. This paper summarizes 13 contributions to Genetic Analysis Workshop 13, which include a wide range of methods for genetic analysis of longitudinal data in families. The methods can be grouped into two basic approaches: 1) two-step modeling, in which repeated observations are first reduced to one summary statistic per subject (e.g., a mean or slope), after which this statistic is used in a standard genetic analysis, or 2) joint modeling, in which genetic and longitudinal model parameters are estimated simultaneously in a single analysis. In applications to Framingham Heart Study data, contributors collectively reported evidence for genes that affected trait mean on chromosomes 1, 2, 3, 5, 8, 9, 10, 13, and 17, but most did not find genes affecting slope. Applications to simulated data suggested that even for a gene that only affected slope, use of a mean-type statistic could provide greater power than a slope-type statistic for detecting that gene. We report on the results of a small experiment that sheds some light on this apparently paradoxical finding, and indicate how one might form a more powerful test for finding a slope-affecting gene. Several areas for future research are discussed.

Cardiovascular Diseases↗

PubMedDate not supplied

The early 1990s cigarette price decrease and trends in youth smoking in Ontario.

BACKGROUND: Youth are especially vulnerable to fluctuations in cigarette price, and both the smuggling increase during the early 1990s and the 1994 tax decrease made purchasing easier for youth. The purpose of this study is to examine the relation between these price decreases, and trends in smoking prevalence and amount smoked among Ontario youth. METHODS: Data from the Ontario Student Drug Use Survey were analyzed for trend using: 1) polynomial regression, and 2) discontinuity regression with an "event time" of 1993 to capture effects of both pre-tax cut smuggling and the tax cut. RESULTS: Overall, smoking prevalence decreased from 1977 to 1993, jumped upward at this time, and decreased after 1993. Among daily smokers, mean number of cigarettes smoked daily showed an increase followed by a decrease over the 24 years, and a negative quadratic trend. Trends for subgroups are also reported. CONCLUSIONS: These findings suggest that the early 1990s cigarette price decrease may have played a role in increasing youth smoking in Ontario.

Adolescent↗

PubMedDate not supplied

Support for tobacco control policies: how congruent are the attitudes of legislators and the public?

OBJECTIVES: To examine the congruence in perceptions and attitudes of legislators and the public regarding tobacco and tobacco control policies. METHODS: Two cross-sectional surveys were used, one of elected federal and provincial legislators and one of adult residents in Ontario, Canada. Perceptions and attitudes were analyzed as dependent variables using multiple logistic regression, and adjusted for age, sex, educational attainment, and smoking status. FINDINGS: Congruence was found in most instances, however, some differences were found. Legislators were more likely than the public to agree that most smokers are addicted and were more supportive of a smoking ban in workplaces, but these differences disappeared after controlling for socio-demographic characteristics. Legislators were also more aware than the public of the magnitude of deaths due to tobacco compared to alcohol, whereas the public was more supportive of strong penalties against stores that sell cigarettes to minors. CONCLUSIONS: Our findings provide considerable evidence for congruence in the "real-world" (unadjusted) perceptions and attitudes of Ontario legislators and the Ontario public toward tobacco control policies. Such findings are positive for tobacco control advocates and should be leveraged to bring forward strong tobacco policies in the political arena.

Adult↗