Transcriptional survey of peripheral blood links lower oxygen saturation during sleep with reduced expressions of CD1D and RAB20 that is reversed by CPAP therapy

Sleep Disordered Breathing (SDB) is associated with a wide range of physiological changes due, in part, to the influence of hypoxemia during sleep. We studied gene expression in peripheral blood mononuclear cells in association with three measures of SDB: Apnea Hypopnea Index (AHI); average oxyhemoglobin saturation (avgO2) during sleep; and minimum oxyhemoglobin saturation (minO2) during sleep. We performed discovery association analysis in two community-based studies, the Framingham Offspring Study (FOS; N=571) and the Multi-Ethnic Study of Atherosclerosis (MESA; N = 580). An association with false discovery rate (FDR) q < 0.05 in one study was considered "replicated" if a p < 0.05 was observed in the other study. Those genes that replicated across MESA and FOS, or with FDR q < 0.05 in meta-analysis, were used for analysis of gene expression in the blood of 15 participants from the Heart Biomarkers In Apnea Treatment (HeartBEAT) trial. HeartBEAT participants had moderate or severe obstructive sleep apnea (OSA) and were studied pre- and post-treatment (three months) with continuous positive airway pressure (CPAP). We also performed Gene Set Enrichment Analysis (GSEA) on all traits and cohort analyses. Twenty-two genes were associated with SDB traits in both MESA and FOS. Of these, lower expression of CD1D and RAB20 was associated with lower avgO2 in MESA and FOS. CPAP treatment increased the expression of these genes in HeartBEAT participants. Immunity and inflammation pathways were up-regulated in subjects with lower avgO2; i.e., in those with a more severe SDB phenotype (MESA), whereas immuno-inflammatory processes were down-regulated in response to CPAP treatment (HeartBEAT). One Sentence SummaryWe studied the association of gene expression in blood with obstructive sleep apnea traits, including oxygen saturation during sleep, and identified mechanisms that are reversed by treatment with Continuous Positive Airway Pressure.