Genetic associations between sleep traits and cognitive ageing outcomes in the Hispanic Community Health Study/Study of Latinos

Yuan Zhang, Michael Elgart, Einat Granot-Hershkovitz, Heming Wang, Wassim Tarraf, Alberto R. Ramos, Ariana M. Stickel, Donglin Zeng, Tanya P. Garcia, Fernando D. Testai, Sylvia Wassertheil-Smoller, Carmen R. Isasi, Martha L. Daviglus, Robert Kaplan, Myriam Fornage, Charles DeCarli, Susan Redline, Hector M. González, Tamar Sofer

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Sleep phenotypes have been reported to be associated with cognitive ageing outcomes. However, there is limited research using genetic variants as proxies for sleep traits to study their associations. We estimated associations between Polygenic Risk Scores (PRSs) for sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnoea (OSA) and measures of cogntive ageing in Hispanic/Latino adults. Methods: We used summary statistics from published genome-wide association studies to construct PRSs representing the genetic basis of each sleep trait, then we studied the association of the PRSs of the sleep phenotypes with cognitive outcomes in the Hispanic Community Healthy Study/Study of Latinos. The primary model adjusted for age, sex, study centre, and measures of genetic ancestry. Associations are highlighted if their p-value <0.05. Findings: Higher PRS for insomnia was associated with lower global cognitive function and higher risk of mild cognitive impairment (MCI) (OR = 1.20, 95% CI [1.06, 1.36]). Higher PRS for daytime sleepiness was also associated with increased MCI risk (OR = 1.14, 95% CI [1.02, 1.28]). Sleep duration PRS was associated with reduced MCI risk among short and normal sleepers, while among long sleepers it was associated with reduced global cognitive function and with increased MCI risk (OR = 1.40, 95% CI [1.10, 1.78]). Furthermore, adjustment of analyses for the measured sleep phenotypes and APOE-ε4 allele had minor effects on the PRS associations with the cognitive outcomes. Interpretation: Genetic measures underlying insomnia, daytime sleepiness, and sleep duration are associated with MCI risk. Genetic and self-reported sleep duration interact in their effect on MCI. Funding: Described in Acknowledgments.

Original languageEnglish (US)
Article number104393
JournalEBioMedicine
Volume87
DOIs
StatePublished - Jan 2023

Keywords

  • Daytime sleepiness
  • Global cognitive function
  • Insomnia
  • Mild cognitive impairment
  • Polygenetic risk score
  • Sleep duration

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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