Dataset Information

Performance of cancer cluster Q-statistics for case-control residential histories.

ABSTRACT: Few investigations of health event clustering have evaluated residential mobility, though causative exposures for chronic diseases such as cancer often occur long before diagnosis. Recently developed Q-statistics incorporate human mobility into disease cluster investigations by quantifying space- and time-dependent nearest neighbor relationships. Using residential histories from two cancer case-control studies, we created simulated clusters to examine Q-statistic performance. Results suggest the intersection of cases with significant clustering over their life course, Q(i), with cases who are constituents of significant local clusters at given times, Q(it), yielded the best performance, which improved with increasing cluster size. Upon comparison, a larger proportion of true positives were detected with Kulldorf's spatial scan method if the time of clustering was provided. We recommend using Q-statistics to identify when and where clustering may have occurred, followed by the scan method to localize the candidate clusters. Future work should investigate the generalizability of these findings.

SUBMITTER: Sloan CD

PROVIDER: S-EPMC3582034 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Performance of cancer cluster Q-statistics for case-control residential histories.

Sloan Chantel D CD Jacquez Geoffrey M GM Gallagher Carolyn M CM Ward Mary H MH Raaschou-Nielsen Ole O Nordsborg Rikke Baastrup RB Meliker Jaymie R JR

Spatial and spatio-temporal epidemiology 20120924 4

Few investigations of health event clustering have evaluated residential mobility, though causative exposures for chronic diseases such as cancer often occur long before diagnosis. Recently developed Q-statistics incorporate human mobility into disease cluster investigations by quantifying space- and time-dependent nearest neighbor relationships. Using residential histories from two cancer case-control studies, we created simulated clusters to examine Q-statistic performance. Results suggest the ...[more]

PMID: 23149326

Similar Datasets

Project description:BackgroundMethods for analyzing space-time variation in risk in case-control studies typically ignore residential mobility. We develop an approach for analyzing case-control data for mobile individuals and apply it to study bladder cancer in 11 counties in southeastern Michigan. At this time data collection is incomplete and no inferences should be drawn - we analyze these data to demonstrate the novel methods. Global, local and focused clustering of residential histories for 219 cases and 437 controls is quantified using time-dependent nearest neighbor relationships. Business address histories for 268 industries that release known or suspected bladder cancer carcinogens are analyzed. A logistic model accounting for smoking, gender, age, race and education specifies the probability of being a case, and is incorporated into the cluster randomization procedures. Sensitivity of clustering to definition of the proximity metric is assessed for 1 to 75 k nearest neighbors.ResultsGlobal clustering is partly explained by the covariates but remains statistically significant at 12 of the 14 levels of k considered. After accounting for the covariates 26 Local clusters are found in Lapeer, Ingham, Oakland and Jackson counties, with the clusters in Ingham and Oakland counties appearing in 1950 and persisting to the present. Statistically significant focused clusters are found about the business address histories of 22 industries located in Oakland (19 clusters), Ingham (2) and Jackson (1) counties. Clusters in central and southeastern Oakland County appear in the 1930's and persist to the present day.ConclusionThese methods provide a systematic approach for evaluating a series of increasingly realistic alternative hypotheses regarding the sources of excess risk. So long as selection of cases and controls is population-based and not geographically biased, these tools can provide insights into geographic risk factors that were not specifically assessed in the case-control study design.

Project description:Identifying genomic regions that descended from a common ancestor is important for understanding the function and evolution of genomes. In distantly related genomes, clusters of homologous gene pairs are evidence of candidate homologous regions. Demonstrating the statistical significance of such "gene clusters" is an essential component of comparative genomic analyses. However, currently there are no practical statistical tests for gene clusters that model the influence of the number of homologs in each gene family on cluster significance. In this work, we demonstrate empirically that failure to incorporate gene family size in gene cluster statistics results in overestimation of significance, leading to incorrect conclusions. We further present novel analytical methods for estimating gene cluster significance that take gene family size into account. Our methods do not require complete genome data and are suitable for testing individual clusters found in local regions, such as contigs in an unfinished assembly. We consider pairs of regions drawn from the same genome (paralogous clusters), as well as regions drawn from two different genomes (orthologous clusters). Determining cluster significance under general models of gene family size is computationally intractable. By assuming that all gene families are of equal size, we obtain analytical expressions that allow fast approximation of cluster probabilities. We evaluate the accuracy of this approximation by comparing the resulting gene cluster probabilities with cluster probabilities obtained by simulating a realistic, power-law distributed model of gene family size, with parameters inferred from genomic data. Surprisingly, despite the simplicity of the underlying assumption, our method accurately approximates the true cluster probabilities. It slightly overestimates these probabilities, yielding a conservative test. We present additional simulation results indicating the best choice of parameter values for data analysis in genomes of various sizes and illustrate the utility of our methods by applying them to gene clusters recently reported in the literature. Mathematical code to compute cluster probabilities using our methods is available as supplementary material.

Dataset Information

Performance of cancer cluster Q-statistics for case-control residential histories.

Publications

Performance of cancer cluster Q-statistics for case-control residential histories.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets