APOE alleles’ association with cognitive function differs across Hispanic/Latino groups and genetic ancestry in the study of Latinos-investigation of neurocognitive aging (HCHS/SOL)

Einat Granot-Hershkovitz, Wassim Tarraf, Nuzulul Kurniansyah, Martha Daviglus, Carmen R. Isasi, Robert Kaplan, Melissa Lamar, Krista M. Perreira, Sylvia Wassertheil-Smoller, Ariana Stickel, Bharat Thyagarajan, Donglin Zeng, Myriam Fornage, Charles S. DeCarli, Hector M. González, Tamar Sofer

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Introduction: Apolipoprotein E (APOE) alleles are associated with cognitive decline, mild cognitive impairment (MCI), and Alzheimer's disease in Whites, but have weaker and inconsistent effects reported in Latinos. We hypothesized that this heterogeneity is due to ancestry-specific genetic effects. Methods: We investigated the associations of the APOE alleles with significant cognitive decline and MCI in 4183 Latinos, stratified by six Latino backgrounds, and explored whether the proportion of continental genetic ancestry (European, African, and Amerindian) modifies these associations. Results: APOE ε4 was associated with an increased risk of significant cognitive decline (odds ratio [OR] = 1.15, P-value = 0.03), with the strongest association in Cubans (OR = 1.46, P-value = 0.007). APOE-ε2 was associated with decreased risk of MCI (OR = 0.37, P-value = 0.04) in Puerto Ricans. Amerindian genetic ancestry was found to protect from the risk conferred by APOE ε4 on significant cognitive decline. Discussion: Results suggest that APOE alleles' effects on cognitive outcomes differ across six Latino backgrounds and are modified by continental genetic ancestry.

Original languageEnglish (US)
Pages (from-to)466-474
Number of pages9
JournalAlzheimer's and Dementia
Volume17
Issue number3
DOIs
StatePublished - Mar 2021

Keywords

  • Alzheimer's disease
  • Hispanics/Latinos
  • admixture
  • ancestry
  • apolipoprotein E
  • cognitive decline
  • genetic epidemiology
  • mild cognitive impairment

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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