Public Health.

Background: Racial differences in dementia prevalence and incidence were found with higher dementia burden in African descendants. Previous neuropathological studies were conducted mostly in white participants in convenience samples. Further studies in diverse populations are important to foster the understanding of race differences in dementia pathology.

Public Health.

Background: The outcomes of extensive Genome-Wide Association Study (GWAS) data in Polygenic Risk Score (PRS) studies exhibit varying odds ratios (ORs), ranging from 1.13 (Bellenguez) to 1.34 (Kunkle).

Motivations, perceptions and impacts of direct-to-consumer genetic testing among users in Brazil.

Numerous studies have focused on direct-to-consumer genetic testing (DTC-GT), but little is known about consumers outside North America and Europe. Therefore, this study assesses the sociodemographic profile, motivations, and impacts of DTC-GT among Brazilian consumers. DTC-GT customers were invited to complete a 30-question online survey anonymously.

The MICA deletion across different populations.

The MICA gene encodes a glycoprotein upregulated upon cellular stress, particularly in oxidative stress, intracellular infections, and tumorigenesis. This stress-signaling molecule interacts with the activating receptor NKG2D from Natural Killer (NK) and some T lymphocytes, stimulating their cytotoxic activity. MICA is encoded within the human Major Histocompatibility Complex next to the HLA-B locus and is highly polymorphic.

Hypertension may associate with cerebral small vessel disease and infarcts through the pathway of intracranial atherosclerosis.

Hypertension, a major modifiable risk factor for cardiovascular diseases, is linked to late-life neurocognitive disorders such as vascular dementia and Alzheimer's disease (AD). This study explores the associations between hypertension, intracranial atherosclerotic disease (ICAD), cerebral small vessel disease (cSVD), and Alzheimer's disease neuropathologic change (ADNC) in a large community-based autopsy study. This cross-sectional study used data from the Biobank for Aging Studies of the University of São Paulo Medical School.

Anti-RBD IgG antibodies from endemic coronaviruses do not protect against the acquisition of SARS-CoV-2 infection among exposed uninfected individuals.

Background: The Coronaviridae family comprises seven viruses known to infect humans, classified into alphacoronaviruses (HCoV-229E and HCoV-NL63) and betacoronaviruses (HCoV-OC43 and HCoV-HKU1), which are considered endemic. Additionally, it includes SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome), and the novel coronavirus SARS-CoV-2, responsible for COVID-19. SARS-CoV-2 induces severe respiratory complications, particularly in the elderly, immunocompromised individuals and those with underlying diseases.

Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer's disease pathology: a population-based autopsy study in an admixed sample.

Background: Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample.

18th International HLA and Immunogenetics Workshop: Report on the SNP-HLA Reference Consortium (SHLARC) component.

The SNP-HLA Reference Consortium (SHLARC), a component of the 18th International HLA and Immunogenetics Workshop, is aimed at collecting diverse and extensive human leukocyte antigen (HLA) data to create custom reference panels and enhance HLA imputation techniques. Genome-wide association studies (GWAS) have significantly contributed to identifying genetic associations with various diseases. The HLA genomic region has emerged as the top locus in GWAS, particularly in immune-related disorders.

Apolipoprotein E ε2 allele is associated with lower risk of carotid artery obstruction in a population-based autopsy study.

Introduction: Apolipoprotein E (APOE) ε4 allele has been associated with higher carotid atherosclerosis risk, while the APOE-ε2 seems to decrease this risk. Data from autopsy studies, where carotid arteries can be evaluated in their full extension, is scarce. Therefore, we investigated the association between APOE alleles and direct morphometric measurements of carotid atherosclerosis in an autopsy study with an admixed sample.

Identification of pathogenic variants in the Brazilian cohort with Familial hypercholesterolemia using exon-targeted gene sequencing.

Familial hypercholesterolemia (FH) is a monogenic disease characterized by high plasma low-density lipoprotein cholesterol (LDL-c) levels and increased risk of premature atherosclerotic cardiovascular disease. Mutations in FH-related genes account for 40% of FH cases worldwide. In this study, we aimed to assess the pathogenic variants in FH-related genes in the Brazilian FH cohort FHBGEP using exon-targeted gene sequencing (ETGS) strategy.

Dynamics of the personalities of PCSK9 on missense variants (rs505151 and rs562556) from elderly cohort studies in Brazil.

The Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) promotes the degradation of the low-density lipoprotein receptors (LDLR). Gain-of-function (GOF) variants of PCSK9 significantly affects lipid metabolism leading to coronary artery disease (CAD), owing to the raising the plasma low-density lipoprotein (LDL). Considering the public health matter, large-scale genomic studies have been conducted worldwide to provide the genetic architecture of populations for the implementation of precision medicine actions.

Immunogenetics of HLA-B: SNP, allele, and haplotype diversity in populations from different continents and ancestry backgrounds.

HLA-B is among the most variable gene in the human genome. This gene encodes a key molecule for antigen presentation to CD8+ T lymphocytes and NK cell modulation. Despite the myriad of studies evaluating its coding region (with an emphasis on exons 2 and 3), few studies evaluated introns and regulatory sequences in real population samples.

Apolipoprotein E genotypes were not associated with intracranial atherosclerosis: a population-based autopsy study.

Background: Apolipoprotein E gene (APOE) ε4 allele is associated with a higher risk of carotid atherosclerosis, but less is known about the association of APOE with intracranial atherosclerotic disease (IAD). We aimed to investigate the association of APOE alleles with IAD in a cross-sectional autopsy study.

Methods: We measured the stenosis in the 12 arteries of the Circle of Willis using postmortem morphometric measurements.

Global and local ancestry modulate APOE association with Alzheimer's neuropathology and cognitive outcomes in an admixed sample.

Dementia is more prevalent in Blacks than in Whites, likely due to a combination of environmental and biological factors. Paradoxically, clinical studies suggest an attenuation of APOE ε4 risk of dementia in African ancestry (AFR), but a dearth of neuropathological data preclude the interpretation of the biological factors underlying these findings, including the association between APOE ε4 risk and Alzheimer's disease (AD) pathology, the most frequent cause of dementia. We investigated the interaction between African ancestry, AD-related neuropathology, APOE genotype, and functional cognition in a postmortem sample of 400 individuals with a range of AD pathology severity and lack of comorbid neuropathology from a cohort of community-dwelling, admixed Brazilians.

Extreme phenotypes approach to investigate host genetics and COVID-19 outcomes.

COVID-19 comprises clinical outcomes of SARS-CoV-2 infection and is highly heterogeneous, ranging from asymptomatic individuals to deceased young adults without comorbidities. There is growing evidence that host genetics play an important role in COVID-19 severity, including inborn errors of immunity, age-related inflammation and immunosenescence. Here we present a brief review on the known order of events from infection to severe system-wide disturbance due to COVID-19 and summarize potential candidate genes and pathways.

Genomics, epigenomics and pharmacogenomics of familial hypercholesterolemia (FHBGEP): A study protocol.

Background: Familial hypercholesterolemia (FH) is a genetic disease that affects millions of people worldwide.

Objectives: The study protocol FHBGEP was design to investigate the main genomic, epigenomic, and pharmacogenomic factors associated with FH and polygenic hypercholesterolemia (PH).

Methods: FH patients will be enrolled at six research centers in Brazil.

Publisher Correction: Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells.

The original PDF version of this Article contained errors in the spelling of Luiz Carlos Caires-Júnior, Uirá Souto Melo, Bruno Henrique Silva Araujo, Alessandra Soares-Schanoski, Murilo Sena Amaral, Kayque Alves Telles-Silva, Vanessa van der Linden, Helio van der Linden, João Ricardo Mendes de Oliveira, Nivia Maria Rodrigues Arrais, Joanna Goes Castro Meira, Ana Jovina Barreto Bispo, Esper Abrão Cavalheiro, and Robert Andreata-Santos, which were incorrectly given as Luiz Carlos de Caires Jr., UiráSouto Melo, Bruno Silva Henrique Araujo, Alessandra Soares Schanoski, MuriloSena Amaral, Kayque Telles Alves Silva, Vanessa Van der Linden, Helio Van der Linden, João Mendes Ricardo de Oliveira, Nivia Rodrigues Maria Arrais, Joanna Castro Goes Meira, Ana JovinaBarreto Bispo, EsperAbrão Cavalheiro, and Robert Andreata Santos. Furthermore, in both the PDF and HTML versions of the Article, the top panel of Fig.

Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells.

Congenital Zika syndrome (CZS) causes early brain development impairment by affecting neural progenitor cells (NPCs). Here, we analyze NPCs from three pairs of dizygotic twins discordant for CZS. We compare by RNA-Seq the NPCs derived from CZS-affected and CZS-unaffected twins.

Diabetes is Not Associated with Alzheimer's Disease Neuropathology.

Background: Previous evidence linking diabetes to Alzheimer's disease (AD) neuropathology is mixed and scant data are available from low- and middle-income countries.

Objective: To investigate the association between diabetes and AD neuropathology in a large autopsy study of older Brazilian adults.

Methods: In this cross-sectional study, diabetes was defined by diagnosis during life or use of antidiabetic medication.

High phenotypic variability in Gerstmann-Sträussler-Scheinker disease.

Gerstmann-Sträussler-Scheinker is a genetic prion disease and the most common mutation is p.Pro102Leu. We report clinical, molecular and neuropathological data of seven individuals, belonging to two unrelated Brazilian kindreds, carrying the p.

Neuropathological diagnoses and clinical correlates in older adults in Brazil: A cross-sectional study.

Background: Clinicopathological studies are important in determining the brain lesions underlying dementia. Although almost 60% of individuals with dementia live in developing countries, few clinicopathological studies focus on these individuals. We investigated the frequency of neurodegenerative and vascular-related neuropathological lesions in 1,092 Brazilian admixed older adults, their correlation with cognitive and neuropsychiatric symptoms, and the accuracy of dementia subtype diagnosis.

Exomic variants of an elderly cohort of Brazilians in the ABraOM database.

Brazilians are highly admixed with ancestry from Europe, Africa, America, and Asia and yet still underrepresented in genomic databanks. We hereby present a collection of exomic variants from 609 elderly Brazilians in a census-based cohort (SABE609) with comprehensive phenotyping. Variants were deposited in ABraOM (Online Archive of Brazilian Mutations), a Web-based public database.