Assessing numerical dependence in gene expression summaries with the jackknife expression difference.

Statistical methods to test for differential expression traditionally assume that each gene's expression summaries are independent across arrays. When certain preprocessing methods are used to obtain those summaries, this assumption is not necessarily true. In general, the erroneous assumption of dependence results in a loss of statistical power. We introduce a diagnostic measure of numerical dependence for gene expression summaries from any preprocessing method and discuss the relative performance of several common preprocessing methods with respect to this measure. Some common preprocessing methods introduce non-trivial levels of numerical dependence. The issue of (between-array) dependence has received little if any attention in the literature, and researchers working with gene expression data should not take such properties for granted, or they risk unnecessarily losing statistical power.

ß-AR polymorphisms and glycemic and lipid parameters in hypertensive individuals receiving carvedilol or metoprolol.

BACKGROUND: ß-Blocker therapy and ß-adrenergic receptor (ß-AR) polymorphisms are associated with increases in glucose and lipid levels. We investigated associations of common ß1 and ß2-AR single-nucleotide polymorphisms (SNPs) with metabolic and lipid variables, and examined interactions with ß-blocker treatment assignment to affect these parameters. METHODS: This was a post hoc analysis of a double-blinded clinical trial of nondiabetic, hypertensive individuals that were randomized to receive carvedilol or metoprolol succinate. Fasting glucose, insulin, and lipid levels were measured at baseline, 3 months, and after 6 months. Genotypes for ß1-AR SNPs Ser49Gly & Gly389Arg and ß2-AR Arg16Gly & Gln27Glu were determined. Multivariable mixed models were used to examine associations between ß-AR polymorphisms, metabolic parameters, and SNP interactions with ß-blocker therapy (p(interaction)). RESULTS: The 322 subjects were mean (s.d.) 51.5 (11.2) years old. After 6 months, insulin levels increased by 35.6% on metoprolol and 9.9% on carvedilol (P = 0.015). In univariate models, the Gln27Gln genotype had higher overall insulin levels with ß-blockade compared to the Glu27Glu genotype (P = 0.006). Both Arg16Gly (P = 0.012) and Gln27Glu (P = 0.037) SNPs were associated with higher triglycerides levels. An interaction between the Arg16Gly SNP and treatment was identified (p(int) = 0.048). CONCLUSIONS: These data suggest that insulin and triglycerides may be influenced by ß2-AR polymorphisms in patients taking ß blockers.

metahdep: meta-analysis of hierarchically dependent gene expression studies.

UNLABELLED: The metahdep package contains tools for combining the results of multiple gene expression studies. Unlike previous microarray meta-analysis packages, metahdep accounts for both sampling and hierarchical dependence among studies, as well as fundamental covariate differences between studies. AVAILABILITY: http://bioconductor.org/packages/release/Software.html