# Alzheimer's disease genetic architecture in the Portuguese population

> **NIH NIH R01** · VAN ANDEL RESEARCH INSTITUTE · 2022 · $889,196

## Abstract

PROJECT SUMMARY
Even though several genes, mutations and genetic variants have been identified to have key roles in
Alzheimer’s disease (AD), these findings have not yet been translated into effective treatments. In order to
increase our chances of identifying successful drug targets it is critical to identify new genetic causes and risk
factors of AD. Our long-term goal is therefore to use genetic approaches to identify therapeutic targets for the
prevention, onset delay or treatment of AD.
Taking advantage of the unique genetic background of an understudied population, this application’s main
objective is to identify novel genes and genetic factors involved in AD. The proposed research focuses on the
Portuguese population because of its unique genetic profile; although quite homogeneous and mainly
European, the genetic profile of this population is enriched by contributions from North and Sub-Saharan
African as well as from Sephardic Jewish populations. Moreover, the high number of early-onset cases and of
families with several generations affected by AD, indicates a strong genetic contribution in the Portuguese
population, despite the low frequency of known AD mutations. Our preliminary studies also show that the
frequency of risk variants differs substantially from other populations.
Specifically, common and rare genetic risk variants associated with AD will be identified by using a
combination of whole genome genotyping, genome-wide association study (GWAS) analyses, and imputation
in a Portuguese sample set. These data will then be used to perform a multi-ethnic GWAS by incorporating
publicly available data from other populations, allowing the increase of diversity and statistical power of our
GWAS. In addition, the genetic characterization of familial and early-onset AD cases in the Portuguese
population will be carried out by performing whole genome sequencing. Analyses in multiplex families lacking
coding mutations in the known AD-causing genes and in a sub-group of early-onset AD cases will allow the
identification of variants with strong effects in disease.
Together these data will allow the identification of common, rare and very rare variants with different effects in
AD. The proposed research will also allow the comparison and integration with data generated from worldwide
populations leading to i) a substantial increase in diversity and statistical power of the currently available
genetic analyses in AD, and ii) the development of a publicly available database and interactive map
(accessible via Alzforum) reporting the different genetic contributions to AD across populations.

## Key facts

- **NIH application ID:** 10438804
- **Project number:** 5R01AG067426-03
- **Recipient organization:** VAN ANDEL RESEARCH INSTITUTE
- **Principal Investigator:** Rita Guerreiro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $889,196
- **Award type:** 5
- **Project period:** 2020-05-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438804

## Citation

> US National Institutes of Health, RePORTER application 10438804, Alzheimer's disease genetic architecture in the Portuguese population (5R01AG067426-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10438804. Licensed CC0.

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