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

Sleep Med. 2018 Jul;47:106-112. doi: 10.1016/j.sleep.2017.12.010. Epub 2018 Jan 12.

Abstract

Introduction: Sleepiness 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).

Methods: Adults (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.

Results: We 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].

Conclusion: We present data for a novel genetic association with sleepiness for an SNP on the PDE4D gene, rs12522161.

Keywords: Genetic epidemiology; Sleep/wake mechanisms; Sleepiness.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alleles
  • Body Mass Index
  • Brazil
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / physiopathology
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Molecular Epidemiology*
  • Polymorphism, Single Nucleotide
  • Polysomnography
  • Risk Factors
  • Sleepiness*
  • Surveys and Questionnaires

Substances

  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • PDE4D protein, human