APOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study

Neurology. 2004 Aug 24;63(4):664-8. doi: 10.1212/01.wnl.0000134671.99649.32.


Background: Obstructive sleep apnea/hypopnea (OSAH) has a strong heritable component, although its genetic basis remains largely unknown. One epidemiologic study found a significant association between the APOE epsilon4 allele and OSAH in middle-aged adults, a finding that was not replicated in a cohort of elderly adults. The objective of this study was to further examine the association of the APOE epsilon4 allele with OSAH in a community-dwelling cohort, exploring age dependency of the association.

Methods: A genetic association study was performed, nested within a prospective cohort study of the cardiovascular consequences of OSAH. Unattended, in-home nocturnal polysomnography was used to measure apnea-hypopnea index (AHI) in 1,775 participants age 40 to 100 years. OSAH was defined as an AHI > or = 15. The relation of APOE genotype to prevalent OSAH was analyzed using generalized estimating equations to account for non-independent observations of individuals from the same sibship.

Results: At least one APOE epsilon4 allele was present in 25% of subjects, with 1.3% epsilon4/epsilon4 homozygotes. The prevalence of OSAH was 19%. After adjustment for age, sex, and BMI, the presence of any APOE epsilon4 allele was associated with increased odds of OSAH (OR 1.41, 95% CI 1.06 to 1.87, p = 0.02). The effect was approximately twice as great in subjects <75 (OR 1.61, CI 1.02 to 2.54) as in those > or =75 years old (OR 1.32, CI 0.91 to 1.90). Exploratory analyses revealed that the strongest effect of APOE epsilon4 was in subjects age <65 (OR 3.08, CI 1.43 to 6.64), and was stronger in those with hypertension or cardiovascular disease than in those without.

Conclusion: The APOE epsilon4 allele is associated with increased risk of OSAH, particularly in individuals under age 65. The mechanisms underlying this association are uncertain. Age-dependency of the APOE-OSAH association may explain previous conflicting results.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Alleles
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Cardiovascular Diseases / epidemiology
  • Cohort Studies
  • Comorbidity
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Hyperlipidemias / epidemiology
  • Hypertension / epidemiology
  • Male
  • Middle Aged
  • Obesity / epidemiology
  • Polysomnography
  • Sleep Apnea, Obstructive / epidemiology
  • Sleep Apnea, Obstructive / genetics*
  • Smoking / epidemiology


  • Apolipoprotein E4
  • Apolipoproteins E