Abstract Details

Title Using the Lens of Local Ancestry to Focus Risk in Alzheimer Disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S4 - Aging and Dementia: Risk Factors and Genetics (2:00 PM-2:12 PM)

Poster/Presentation
Number 006

Objective Our objective is to assess the effect of Southern European (SE) genetic ancestry on APOE gene using Caribbean Hispanic Puerto Rican (CHIPR) population

Background

Alzheimer disease (AD) is a progressive neurodegenerative disease and occurs in all ethnic and racial groups. The APOE ε4 allele is a major risk factor for AD whose effect shows strong racial/ethnic differences. Among the non-Hispanic White populations APOE shows the strongest effect in North Europeans and has a relatively lower effect in SE populations. Hispanic/Latino populations with a large proportion of SE ancestry provides a unique opportunity to assess the role of SE ancestry in AD. Thus, our goal to assess the relevance of the SE genetic ancestry to the differential effect of the APOE using CHIPR population.

Design/Methods

APOE and genome-wide genotyping were performed in 412 CHPR (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.

Results The admixture analysis showed that the origin of European ancestry in CHIPR is from SE. The distribution of the parental ancestries local to the APOE gene was 68% SE, 20% AF, and 12% AI. Logistic regression model showed significant association of the APOE ε4 risk allele with AD (CHIPR: OR = 1.9 CI:1.3-2.8, p-value = 4.4e-4).

Conclusions Our results showed that the effect of the ε4 risk allele in CHIPR with the dominantly (~67%) SE ancestral background is less than it was observed in overall NHW population and close to APOE effect observed in the population from the Iberian Peninsula. Our data support the findings that suggests an interaction between the genetic risk allele ε4 and ancestral backgrounds located around the genomic region of APOE gene.

Authors/Disclosures
Farid Rajabli, PhD (University of Miami) PRESENTER	Farid Rajabli has nothing to disclose.
	No disclosure on file
	No disclosure on file
Jeffery Vance, MD, PhD (University of Miami)	Dr. Vance has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for neurology genetics.
Farid Rajabli, PhD (University of Miami)	Farid Rajabli has nothing to disclose.
Margaret A. Pericak-Vance, PhD (University of Miami Miller School of Medicine)	Dr. Pericak-Vance has nothing to disclose.

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