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

25 Scopus citations


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
Issue number3
StatePublished - Nov 6 2020

Bibliographical note

Funding Information:
The authors thank the staff and participants of HCHS/SOL for their important contributions. Investigators website: http://www.cscc.unc.edu/hchs/ . This work is supported by the National Institute on Aging (R01AG048642, RF1AG054548, RF1AG061022, and R21AG056952). Dr. González also receives additional support from P30AG062429 and P30AG059299. The Hispanic Community Health Study/Study of Latinos is a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (HHSN268201300001I/N01‐HC‐65233), University of Miami (HHSN268201300004I/N01‐HC‐65234), Albert Einstein College of Medicine (HHSN268201300002I/N01‐HC‐65235), University of Illinois at Chicago – HHSN268201300003I/N01‐HC‐65236 Northwestern Univ), and San Diego State University (HHSN268201300005I/N01‐HC‐65237). The following Institutes/Centers/Offices have contributed to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution‐Office of Dietary Supplements. The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03).

Publisher Copyright:
© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association


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


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