The effects of age, cigarette smoking, sex and race on the qualitative characteristics of lung transcriptome

Background: Methods based on within-sample relative expression orderings (REOs) comparisons have been proposed for identifying differentially expressed genes (DEGs) at the individual level and for detecting disease-associated genes based on one-phenotype disease data by reusing data of normal samples from other sources. However, the common potential confounding factors, including age, cigarette smoking, sex and race whether could affect the REOs of gene pairs is still unclear. Methods: For one confounding factor, based on the numbers of related gene pairs or DEGs, we evaluated the effect of this confounding factor on the REOs of gene pairs within normal lung tissues transcriptome. Results: Our results showed that age has little effect on REOs within lung tissues. We found that about 0.23% of the significantly stable REOs of gene pairs in non-smokers’ lung tissues are reversed in smokers’ lung tissues, introduced by 344 DEGs between the two groups of samples (RankCompV2, FDR < 0.05), which are enriched in metabolism of xenobiotics by cytochrome P450, glutathione metabolism and other pathways (hypergeometric test, FDR < 0.05). Comparison between the normal lung tissue samples of males and females revealed fewer reversal REOs introduced by 24 DEGs between the sex groups, among which 19 DEGs are located on sex chromosomes and 5 DEGs involving in spermatogenesis and regulation of oocyte are located on autosomes. Between the normal lung tissue samples of white and black people, we identified 22 DEGs (RankCompV2, FDR < 0.05) which introduced a few reversal REOs between the two races. Conclusions: In summary, the REO-based study should take into account the confounding factors of cigarette smoking, sex and race.