A stepwise likelihood ratio test procedure for rare variant selection in case-control studies.

There is much recent interest in finding rare genetic variants associated with various diseases. Owing to the scarcity of rare mutations, single-variant analyses often lack power. To enable pooling of information across variants, we use a random effect formulation within a retrospective modeling framework that respects the retrospective data collecting mechanism of case-control studies.

Spatial analysis of ambulance response times related to prehospital cardiac arrests in the city-state of Singapore.

Objectives: The main objective of this study was to establish the spatial variation in ambulance response times for out-of-hospital cardiac arrests (OHCAs) in the city-state of Singapore. The secondary objective involved studying the relationships between various covariates, such as traffic condition and time and day of collapse, and ambulance response times.

Methods: The study design was observational and ecological in nature.

Spatial variation and geographic-demographic determinants of out-of-hospital cardiac arrests in the city-state of Singapore.

Study Objective: Our primary objective is to calculate the relative risk of cardiac arrests at the development guide plan (DGP) (equivalent to census tract) level in a city-state, Singapore, and examine its relationship with key area-level population characteristics.

Methods: This was an observational ecological study design. We calculated the relative risk as the ratio of the observed and population standardized expected counts of out-of-hospital cardiac arrests in Singapore, aggregated at DGP level.

Intra- and inter-individual genetic differences in gene expression.

Genetic variation is known to influence the amount of mRNA produced by a gene. Because molecular machines control mRNA levels of multiple genes, we expect genetic variation in components of these machines would influence multiple genes in a similar fashion. We show that this assumption is correct by using correlation of mRNA levels measured from multiple tissues in mouse strain panels to detect shared genetic influences.

Meta-analysis and gene set enrichment relative to er status reveal elevated activity of MYC and E2F in the "basal" breast cancer subgroup.

Background: Breast cancers lacking the estrogen receptor (ER) can be distinguished from other breast cancers on the basis of poor prognosis, high grade, distinctive histopathology and unique molecular signatures. These features further distinguish estrogen receptor negative (ER-) tumor subtypes, but targeted therapy is currently limited to tumors over-expressing the ErbB2 receptor.

Methodology/principal Findings: To uncover the pathways against which future therapies could be developed we undertook a meta-analysis of gene expression from five large microarray datasets relative to ER status.

Genetic dissection of gene regulation in multiple mouse tissues.

The analysis of the influence of genetic variation on regulation of gene expression at a near-genome-wide level has become the focus of much recent interest. It is widely appreciated that many genes are expressed in a tissue-specific manner and that others are more ubiquitously expressed but relatively little is known about how genetic variation might influence these tissue patterns of gene expression. In this review we discuss what is known about the tissue specificity of the influence of genetic variation and review the challenges that we face in combining hugely parallel, microarray-based gene analysis with equally expensive genetic analysis.

Antigen selection in the IgE response of allergic and nonallergic individuals.

Background: Affinity maturation within germinal centers should usually lead to an accumulation of replacement mutations in complementarity-determining regions (CDRs) of Ig genes as a result of antigen selection. A number of studies have suggested, but not statistically demonstrated, that antigen selection might not guide such an accumulation of replacement mutations in allergic IgE sequences. This has been suggested to reflect the nature of allergens themselves or of the allergic response.