Southern European genetic ancestry shows reduced APOE E4 risk for Alzheimer disease in Caribbean Hispanic population: Genetics/genetic factors of Alzheimer's disease. (7th December 2020)

• Record Type: Journal Article
• Authors: Rajabli, Farid; Adams, Larry D.; Tejada, Sergio; Rodriguez, Vanessa C.; Mena, Pedro Ramon; Prough, Michael; Bussies, Parker; Feliciano, Nereida I.; Silva‐Vergara, Concepcion; Contreras, Maricarmen; Hamilton‐Nelson, Kara L.; Acosta, Heriberto; Vance, Jeffery M.; Cuccaro, Michael L.; Feliciano‐Astacio, Briseida E.; Beecham, Gary W.; Pericak‐Vance, Margaret A.
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 3
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.045951
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: The APOE ε4 allele is a major risk factor for AD whose effect shows strong racial/ethnic differences. Among non‐Hispanic White (NHW) populations APOE shows the strongest effect in Northern European (NEu) (rs429358: OR = 3.32, CI:3.20‐3.45) and has a relatively lower effect in Southern European (SEu; i.e., Iberia, Italy, etc) populations (rs429358: OR = 2.27, CI:2.06–2.50). However, it is not clear if this difference in effect is due to genetic or environmental effects. Hispanic/Latino populations with a large proportion of SEu ancestry provide a unique opportunity to assess both global SEu ancestry (i.e., genome‐wide ancestry) and local SEu ancestry (chromosome/region specific ancestry) in populations with environments distinct from SEu. Our objective is to use data from a Caribbean Hispanic Puerto Rican (CHIPR) population to assess the role of SEu genetic ancestry and the APOE gene on Alzheimer disease (AD) risk. Method: APOE and genome‐wide genotyping were performed in 412 CHIPR (231 cases, 181 controls). Local ancestry was calculated using SHAPEIT and RFMix. Global ancestry was assessed using GENESIS. Association between affection status and APOE genotype was analyzed using logistic regression models by adjusting for age, gender, and population substructure. Result: The admixture analysis showed that CHIPR have a substantial SEu ancestral component (∼67%). At the APOE gene, the local ancestry was 68% SEu, 20% African, and 12% Amerindian. Logistic regression model showed a significant association of the APOE ε4 risk allele with AD (CHIPR: OR = 1.9 CI:1.3‐2.8, p‐value = 4.4e‐4). Conclusion: We found that the effect of the APOE ε4 risk allele in CHIPR with the high SEu ancestral background (∼67%) is similar to the effect observed in Southern European populations, despite having a distinct environment. Our results support the hypothesis that SEu genetic ancestry modulates the risk of APOE in CHIPRs. This suggests that subcontinental ancestry could also play an important role in modulating the risk for other known AD candidate. Studying the sub‐continental (NEu and SEu) ethnic disparity in the genetics of AD, provides critical information to advance the development of novel therapeutic measures.