You are here

Dissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population.

TitleDissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population.
Publication TypeJournal Article
Year of Publication2021
AuthorsMarca-Ysabel MVictoria, Rajabli F, Cornejo-Olivas M, Whitehead PG, Hofmann NK, Manrique MZaida Illa, Otani DMartin Vel, Neyra AKarina Mil, Suarez SCastro, Vega MMeza, Adams LD, Mena PR, Rosario I, Cuccaro ML, Vance JM, Beecham GW, Custodio N, Montesinos R, Soler PEMazzetti, Pericak-Vance MA
JournalNeurobiol Aging
Date Published2021 05
KeywordsAlleles, Alzheimer Disease, American Indians or Alaska Natives, Apolipoprotein E4, Female, Genetics, Population, Genome-Wide Association Study, Genotyping Techniques, Heterozygote, Humans, Male, Peru, Risk Factors

Alzheimer disease (AD) is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups. The apolipoprotein E (ApoE) ε4 is the most significant genetic risk factor for late-onset AD and shows the strongest effect among East Asian populations followed by non-Hispanic white populations and has a relatively lower effect in African descent populations. Admixture analysis in the African American and Puerto Rican populations showed that the variation in ε4 risk is correlated with the genetic ancestral background local to the ApoE gene. Native American populations are substantially underrepresented in AD genetic studies. The Peruvian population with up to ~80 of Amerindian (AI) ancestry provides a unique opportunity to assess the role of AI ancestry in AD. In this study, we assess the effect of the ApoE ε4 allele on AD in the Peruvian population. A total of 79 AD cases and 128 unrelated cognitive healthy controls from Peruvian population were included in the study. Genome-wide genotyping was performed using the Illumina Global screening array v2.0. Global ancestry and local ancestry analyses were assessed. The effect of the ApoE ε4 allele on AD was tested using a logistic regression model by adjusting for age, gender, and population substructure (first 3 principal components). Results showed that the genetic ancestry surrounding the ApoE gene is predominantly AI (60.6%) and the ε4 allele is significantly associated with increased risk of AD in the Peruvian population (odds ratio = 5.02, confidence interval: 2.3-12.5, p-value = 2e-4). Our results showed that the risk for AD from ApoE ε4 in Peruvians is higher than we have observed in non-Hispanic white populations. Given the high admixture of AI ancestry in the Peruvian population, it suggests that the AI genetic ancestry local to the ApoE gene is contributing to a strong risk for AD in ε4 carriers. Our data also support the findings of an interaction between the genetic risk allele ApoE ε4 and the ancestral backgrounds located around the genomic region of ApoE gene.

Pubmed Link
Alternate JournalNeurobiol Aging
PubMed ID33541779
PubMed Central IDPMC8122013
Grant ListU01 AG058654 / AG / NIA NIH HHS / United States
RF1 AG054074 / AG / NIA NIH HHS / United States
D43 TW009137 / TW / FIC NIH HHS / United States
D43 TW009345 / TW / FIC NIH HHS / United States
R01 AG070864 / AG / NIA NIH HHS / United States

Theme by Danetsoft and Danang Probo Sayekti inspired by Maksimer