Genome-wide estimation of gender differences in the gene expression of human livers: statistical design and analysis

Gender differences in gene expression were estimated in liver samples from 9 males and 9 females. The study tested 31,110 genes for a gender difference using a design that adjusted for sources of variation associated with cDNA arrays, normalization, hybridizations and processing conditions. The genes were split into 2,800 that were clearly expressed (expressed genes) and 28,310 that had expression levels in the background range (not expressed genes). The distribution of p-values from the 'not expressed' group was consistent with no gender differences. The distribution of p-values from the 'expressed' group suggested that 8% of these genes differed by gender, but the estimated fold-changes (expression in males/expression in females) were small. The largest observed fold-change was 1.55. The 95% confidence bounds on the estimated fold-changes were less than 1.4 fold for 79.3%, and few (1.1%) exceed 2-fold. Observed gender differences in gene expression were small. When selecting genes with gender differences based upon their p-values, false discovery rates exceed 80% for any set of genes, essentially making it impossible to identify any specific genes with a gender difference.