Publications by authors named "Luciana Bertholim Nasciben"
Background: The effect size of APOE4 varies across genetic ancestries with African (AFR) local ancestry conferring a lower risk when compared to other ancestries. Recently, we identified a strong effect of the A allele of rs10423769 (with a minor allele frequency of 0.12 in AFR and 0.
View Article and Find Full Text PDFBackground: In the US, African Americans (admixed with African and European) followed by Hispanics (admixed with Amerindian, African, and European) are the most affected groups compared to non-Hispanic Whites (NHW). While genetic diversity and admixture play crucial roles in disease risk, the ancestry-specific mechanisms remain poorly understood with most AD-related studies focusing on NHW. Despite the recent field efforts to include genetically admixed populations, there continues to be a lack of functional studies in AD across the different cell types in these populations.
View Article and Find Full Text PDFBackground: Non-Hispanic White APOE4 carriers have a higher risk of developing AD compared to African American APOE4 carriers. The local ancestry (LA) surrounding the APOE region was previously shown to be the primary factor in this risk difference. APOE4 carriers of European LA (ELA) have been found to have higher APOE4 expression and chromatin accessibility compared to African LA (ALA).
View Article and Find Full Text PDFBackground: This study aims to elucidate ancestry-specific changes to the genomic regulatory architecture in induced pluripotent stem cell (iPSC)-derived oligodendroglia, focusing on their implications for Alzheimer's disease (AD). This work addresses the lack of diversity in previous iPSC studies by including ancestries that contribute to African American (European/African) and Hispanic/Latino populations (Amerindian/African/European).
Methods: We generated 12 iPSC lines-four African, four Amerindian, and four European- from both AD patients and non-cognitively impaired individuals, with varying genotypes ( and ).
Article Synopsis
- ε4 is the most significant genetic risk factor for Alzheimer's disease (AD), with about half of AD patients having at least one ε4 allele.
- Researchers found that the African-specific A allele of rs10423769 significantly reduces the AD risk associated with ε4 homozygotes by roughly 75%.
- The protective variant is located in a specific region of chromosome 19, demonstrating differences at the structural and DNA methylation levels compared to non-protective variants, and emphasizing the need for diverse ancestry representation in AD studies.
Article Synopsis
- Researchers in pharmacogenomics (PGx) focus on how genetic variations affect drug responses, using whole-genome sequencing (WGS) to study populations, including a cohort of elderly individuals from São Paulo, Brazil.
- The study identified a total of 352 unique star alleles from 38 pharmacogenes and highlighted that 98% of individuals carried at least one genotype linked to a high-risk drug interaction.
- About 42% of the cohort was prescribed drugs known to have significant interactions based on genetic factors, with nearly 19% of these individuals at high risk according to their genetic profiles.
Introduction: Several countries require manufacturers to present a budget impact analysis (BIA), together with a cost-effectiveness analysis, to support national funding requests. However, guidelines for conducting BIA of vaccines are scarce.
Objectives: To analyze the methodological approaches used in published budget impact analysis (BIA) of vaccines, discussing specific methodological issues related to vaccines.