Candidate gene analysis in the São Paulo Epidemiologic Sleep Study (EPISONO) shows an association of variant in PDE4D and sleepiness

Abstract

IntroductionSleepiness and cardiovascular disease share common molecular pathways; thus, genetic risk factors for sleepiness may also predict cardiovascular disease risk. This study explored the associations between subjective sleepiness and single-nucleotide polymorphisms (SNPs) in candidate genes within oxidative stress, inflammatory, and neuronal pathways, which may contribute to sleepiness and downstream cardiovascular disease risk: Cytochrome B-245, Alpha Polypeptide (CYBA), Cytochrome B-245, Beta Polypeptide (CYBB), Neutrophil Cytosolic Factor (NCF2), Tumor Necrosis Factor-Alpha (TNFA), and Phosphodiesterase 4D (PDE4D). MethodsAdults (N = 918) from the general population who were a part of the São Paulo Epidemiologic Sleep Study (EPISONO) in São Paulo, Brazil, were genotyped using Human Omni Express BeadChip array. The average age was 42 ± 14.5 years, subjects had a mean body mass index (BMI) of 26.9 ± 5.4 kg/m2, and 44% were male. Based on the Epworth Sleepiness Scale (ESS), subjects were classified as having sleepiness (ESS ≥ 10) or no sleepiness (ESS < 10). Logistic regression models were used to examine the associations with SNPs within candidate genes and sleepiness, adjusting for age, gender, BMI, Apnea–Hypopnea Index (AHI), total sleep time, and ancestry informative principal components (PCs). Complementary analyses using linear regression to assess the relationship between SNPs and continuous ESS were performed. ResultsWe observed a novel association between the C allele of the rs12522161 SNP on PDE4D and a decreased likelihood of sleepiness, controlling for covariates and ancestry [OR (95% CI) = 0.64 (0.50, 0.81); p = 0.0002]. ConclusionWe present data for a novel genetic association with sleepiness for an SNP on the PDE4D gene, rs12522161.