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Article: Editorial: Genomic Ancestry and Biological Traits.

Rodrigues-Soares, Fernanda / Kehdy, Fernanda S G / Gouveia, Mateus H

2021 Volume 12, Page(s) 754725

Language	English
Publishing date	2021-09-06
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2021.754725
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Article: A case report of vaccine-induced immune thrombotic thrombocytopenia (VITT) with genetic analysis.

Mendes-de-Almeida, Daniela P / Kehdy, Fernanda S G / Martins-Gonçalves, Remy / Bokel, Joanna / Grinsztejn, Eduarda / Mouta Nunes de Oliveira, Patrícia / Maia, Maria de Lourdes de Sousa / Hoagland, Brenda / Wagner Cardoso, Sandra / Grinsztejn, Beatriz / Siqueira, Marilda M / Kurtz, Pedro / Bozza, Patricia T / Garcia, Cristiana C

Frontiers in cardiovascular medicine

2023 Volume 10, Page(s) 1189320

Abstract: The emergence of the rare syndrome called vaccine-induced immune thrombocytopenia and thrombosis (VITT) after adenoviral vector vaccines, including ChAdOx1 nCov-19, raises concern about one's predisposing risk factors. Here we report the case of a 56- ... ...

Abstract	The emergence of the rare syndrome called vaccine-induced immune thrombocytopenia and thrombosis (VITT) after adenoviral vector vaccines, including ChAdOx1 nCov-19, raises concern about one's predisposing risk factors. Here we report the case of a 56-year-old white man who developed VITT leading to death within 9 days of symptom onset. He presented with superior sagittal sinus thrombosis, right frontal intraparenchymal hematoma, frontoparietal subarachnoid and massive ventricular hemorrhage, and right lower extremity arterial and venous thrombosis. His laboratory results showed elevated D-dimer, C-reactive protein, tissue factor, P-selectin (CD62p), and positive anti-platelet factor 4. The patient's plasma promoted higher CD62p expression in healthy donors' platelets than the controls. Genetic investigation on coagulation, thrombophilia, inflammation, and type I interferon-related genes was performed. From rare variants in European or African genomic databases, 68 single-nucleotide polymorphisms (SNPs) in one allele and 11 in two alleles from common SNPs were found in the patient genome. This report highlights the possible relationship between VITT and genetic variants. Additional investigations regarding the genetic predisposition of VITT are needed.
Language	English
Publishing date	2023-05-19
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2023.1189320
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Article ; Online: Genetic structure of pharmacogenetic biomarkers in Brazil inferred from a systematic review and population-based cohorts: a RIBEF/EPIGEN-Brazil initiative.

Rodrigues-Soares, Fernanda / Kehdy, Fernanda S G / Sampaio-Coelho, Julia / Andrade, Poliana X C / Céspedes-Garro, Carolina / Zolini, Camila / Aquino, Marla M / Barreto, Mauricio L / Horta, Bernardo L / Lima-Costa, Maria Fernanda / Pereira, Alexandre C / LLerena, Adrián / Tarazona-Santos, Eduardo

The pharmacogenomics journal

2018 Volume 18, Issue 6, Page(s) 749–759

Abstract: We present allele frequencies involving 39 pharmacogenetic biomarkers studied in Brazil, and their distribution on self-reported race/color categories that: (1) involve a mix of perceptions about ancestry, morphological traits, and cultural/identity ... ...

Abstract	We present allele frequencies involving 39 pharmacogenetic biomarkers studied in Brazil, and their distribution on self-reported race/color categories that: (1) involve a mix of perceptions about ancestry, morphological traits, and cultural/identity issues, being social constructs pervasively used in Brazilian society and medical studies; (2) are associated with disparities in access to health services, as well as in their representation in genetic studies, and (3), as we report here, explain a larger portion of the variance of pharmaco-allele frequencies than geography. We integrated a systematic review of studies on healthy volunteers (years 1968-2017) and the analysis of allele frequencies on three population-based cohorts from northeast, southeast, and south, the most populated regions of Brazil. Cross-validation of results from these both approaches suggest that, despite methodological heterogeneity of the 120 studies conducted on 51,747 healthy volunteers, allele frequencies estimates from systematic review are reliable. We report differences in allele frequencies between color categories that persist despite the homogenizing effect of >500 years of admixture. Among clinically relevant variants: CYP2C92 (null), CYP3A53 (defective), SLCO1B1-rs4149056(C), and VKORC1-rs9923231(A) are more frequent in Whites than in Blacks. Brazilian Native Americans show lower frequencies of CYP2C92, CYP2C1917 (increased activity), and higher of SLCO1B1-rs4149056(C) than other Brazilian populations. We present the most current and informative database of pharmaco-allele frequencies in Brazilian healthy volunteers.
MeSH term(s)	Brazil ; Continental Population Groups/genetics ; Databases, Genetic ; Gene Frequency ; Haplotypes ; Health Status Disparities ; Healthcare Disparities/ethnology ; Heredity ; Humans ; Pedigree ; Pharmacogenetics/methods ; Pharmacogenomic Variants ; Phenotype ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2018-05-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	2106831-8
ISSN	1473-1150 ; 1470-269X
ISSN (online)	1473-1150
ISSN	1470-269X
DOI	10.1038/s41397-018-0015-7
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Article: Human-SARS-CoV-2 interactome and human genetic diversity: TMPRSS2-rs2070788, associated with severe influenza, and its population genetics caveats in Native Americans.

Kehdy, Fernanda S G / Pita-Oliveira, Murilo / Scudeler, Mariana M / Torres-Loureiro, Sabrina / Zolini, Camila / Moreira, Rennan / Michelin, Lucas A / Alvim, Isabela / Silva-Carvalho, Carolina / Furlan, Vinicius C / Aquino, Marla M / Santolalla, Meddly L / Borda, Victor / Soares-Souza, Giordano B / Jaramillo-Valverde, Luis / Vasquez-Dominguez, Andres / Neira, Cesar Sanchez / Aguiar, Renato S / Verdugo, Ricardo A /

O Connor, Timothy D / Guio, Heinner / Tarazona-Santos, Eduardo / Leal, Thiago P / Rodrigues-Soares, Fernanda

Genetics and molecular biology

2021 Volume 44, Issue 1 Suppl 1, Page(s) e20200484

Abstract: For human/SARS-CoV-2 interactome genes ACE2, TMPRSS2 and BSG, there is a convincing evidence of association in Asians with influenza-induced SARS for TMPRSS2-rs2070788, tag-SNP of the eQTL rs383510. This case illustrates the importance of population ... ...

Abstract	For human/SARS-CoV-2 interactome genes ACE2, TMPRSS2 and BSG, there is a convincing evidence of association in Asians with influenza-induced SARS for TMPRSS2-rs2070788, tag-SNP of the eQTL rs383510. This case illustrates the importance of population genetics and of sequencing data in the design of genetic association studies in different human populations: the high linkage disequilibrium (LD) between rs2070788 and rs383510 is Asian-specific. Leveraging on a combination of genotyping and sequencing data for Native Americans (neglected in genetic studies), we show that while their frequencies of the Asian tag-SNP rs2070788 is, surprisingly, the highest worldwide, it is not in LD with the eQTL rs383510, that therefore, should be directly genotyped in genetic association studies of SARS in populations with Native American ancestry.
Language	English
Publishing date	2021-08-25
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	1445712-x
ISSN	1678-4685 ; 1415-4757
ISSN (online)	1678-4685
ISSN	1415-4757
DOI	10.1590/1678-4685-GMB-2020-0484
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Article: Biogeographical ancestry is associated with socioenvironmental conditions and infections in a Latin American urban population.

da Silva, Thiago Magalhães / Fiaccone, Rosemeire L / Kehdy, Fernanda S G / Tarazona-Santos, Eduardo / Rodrigues, Laura C / Costa, Gustavo N O / Figueiredo, Camila A / Alcantara-Neves, Neuza Maria / Barreto, Maurício L

SSM - population health

2018 Volume 4, Page(s) 301–306

Abstract: Racial inequalities are observed for different diseases and are mainly caused by differences in socioeconomic status between ethnoracial groups. Genetic factors have also been implicated, and recently, several studies have investigated the association ... ...

Abstract	Racial inequalities are observed for different diseases and are mainly caused by differences in socioeconomic status between ethnoracial groups. Genetic factors have also been implicated, and recently, several studies have investigated the association between biogeographical ancestry (BGA) and complex diseases. However, the role of BGA as a proxy for non-genetic health determinants has been little investigated. Similarly, studies comparing the association of BGA and self-reported skin colour with these determinants are scarce. Here, we report the association of BGA and self-reported skin colour with socioenvironmental conditions and infections. We studied 1246 children living in a Brazilian urban poor area. The BGA was estimated using 370,539 genome-wide autosomal markers. Standardised questionnaires were administered to the children's guardians to evaluate socioenvironmental conditions. Infection (or pathogen exposure) was defined by the presence of positive serologic test results for IgG to seven pathogens (T
Language	English
Publishing date	2018-03-17
Publishing country	England
Document type	Journal Article
ISSN	2352-8273
ISSN	2352-8273
DOI	10.1016/j.ssmph.2018.03.006
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Article ; Online: Genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America.

Oliveira, Pablo / Costa, Gustavo N O / Damasceno, Andresa K A / Hartwig, Fernando P / Barbosa, George C G / Figueiredo, Camila A / Ribeiro-Silva, Rita de C / Pereira, Alexandre / Lima-Costa, M Fernanda / Kehdy, Fernanda S / Tarazona-Santos, Eduardo / Horta, Bernardo L / Rodrigues, Laura C / Fiaccone, Rosemeire L / Barreto, Maurício L

Scientific reports

2018 Volume 8, Issue 1, Page(s) 14475

Abstract: The genetic architecture of asthma was relatively well explored. However, some work remains in the field to improve our understanding on asthma genetics, especially in non-Caucasian populations and with regards to commonly neglected genetic variants, ... ...

Abstract	The genetic architecture of asthma was relatively well explored. However, some work remains in the field to improve our understanding on asthma genetics, especially in non-Caucasian populations and with regards to commonly neglected genetic variants, such as Copy Number Variations (CNVs). In the present study, we investigated the contribution of CNVs on asthma risk among Latin Americans. CNVs were inferred from SNP genotyping data. Genome wide burden and association analyses were conducted to evaluate the impact of CNVs on asthma outcome. We found no significant difference in the numbers of CNVs between asthmatics and non-asthmatics. Nevertheless, we found that CNVs are larger in patients then in healthy controls and that CNVs from cases intersect significantly more genes and regulatory elements. We also found that a deletion at 6p22.1 is associated with asthma symptoms in children from Salvador (Brazil) and in young adults from Pelotas (Brazil). To support our results, we conducted an in silico functional analysis and found that this deletion spans several regulatory elements, including two promoter elements active in lung cells. In conclusion, we found robust evidence that CNVs could contribute for asthma susceptibility. These results uncover a new perspective on the influence of genetic factors modulating asthma risk.
MeSH term(s)	Adult ; Asthma/ethnology ; Asthma/genetics ; Brazil/ethnology ; Child ; Child, Preschool ; Chromosome Deletion ; Chromosomes, Human, Pair 6/genetics ; Female ; Gene Dosage ; Genetic Predisposition to Disease ; Humans ; Male ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2018-09-27
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-32837-w
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Article ; Online: Genomic ancestry and ethnoracial self-classification based on 5,871 community-dwelling Brazilians (The Epigen Initiative).

Lima-Costa, M Fernanda / Rodrigues, Laura C / Barreto, Maurício L / Gouveia, Mateus / Horta, Bernardo L / Mambrini, Juliana / Kehdy, Fernanda S G / Pereira, Alexandre / Rodrigues-Soares, Fernanda / Victora, Cesar G / Tarazona-Santos, Eduardo

Scientific reports

2015 Volume 5, Page(s) 9812

Abstract: ... genomic ancestry showed a significant S-shape positive association with self-reported Blacks in the three ...

Abstract	Brazil never had segregation laws defining membership of an ethnoracial group. Thus, the composition of the Brazilian population is mixed, and its ethnoracial classification is complex. Previous studies showed conflicting results on the correlation between genome ancestry and ethnoracial classification in Brazilians. We used 370,539 Single Nucleotide Polymorphisms to quantify this correlation in 5,851 community-dwelling individuals in the South (Pelotas), Southeast (Bambui) and Northeast (Salvador) Brazil. European ancestry was predominant in Pelotas and Bambui (median = 85.3% and 83.8%, respectively). African ancestry was highest in Salvador (median = 50.5%). The strength of the association between the phenotype and median proportion of African ancestry varied largely across populations, with pseudo R(2) values of 0.50 in Pelotas, 0.22 in Bambui and 0.13 in Salvador. The continuous proportion of African genomic ancestry showed a significant S-shape positive association with self-reported Blacks in the three sites, and the reverse trend was found for self reported Whites, with most consistent classifications in the extremes of the high and low proportion of African ancestry. In self-classified Mixed individuals, the predicted probability of having African ancestry was bell-shaped. Our results support the view that ethnoracial self-classification is affected by both genome ancestry and non-biological factors.
MeSH term(s)	Adult ; African Continental Ancestry Group/genetics ; Brazil ; Child ; Child, Preschool ; Cohort Studies ; Epigen/genetics ; Ethnic Groups/genetics ; European Continental Ancestry Group/genetics ; Genetics, Population/methods ; Genomics/methods ; Humans ; Longitudinal Studies ; Middle Aged ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Young Adult
Chemical Substances	Epigen
Language	English
Publishing date	2015-04-27
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep09812
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Article ; Online: How Ancestry Influences the Chances of Finding Unrelated Donors: An Investigation in Admixed Brazilians.

Nunes, Kelly / Aguiar, Vitor R C / Silva, Márcio / Sena, Alexandre C / de Oliveira, Danielli C M / Dinardo, Carla L / Kehdy, Fernanda S G / Tarazona-Santos, Eduardo / Rocha, Vanderson G / Carneiro-Proietti, Anna Barbara F / Loureiro, Paula / Flor-Park, Miriam V / Maximo, Claudia / Kelly, Shannon / Custer, Brian / Weir, Bruce S / Sabino, Ester C / Porto, Luís Cristóvão / Meyer, Diogo

Frontiers in immunology

2020 Volume 11, Page(s) 584950

Abstract: A match of HLA loci between patients and donors is critical for successful hematopoietic stem cell transplantation. However, the extreme polymorphism of HLA loci - an outcome of millions of years of natural selection - reduces the chances that two ... ...

Abstract	A match of HLA loci between patients and donors is critical for successful hematopoietic stem cell transplantation. However, the extreme polymorphism of HLA loci - an outcome of millions of years of natural selection - reduces the chances that two individuals will carry identical combinations of multilocus HLA genotypes. Further, HLA variability is not homogeneously distributed throughout the world: African populations on average have greater variability than non-Africans, reducing the chances that two unrelated African individuals are HLA identical. Here, we explore how self-identification (often equated with "ethnicity" or "race") and genetic ancestry are related to the chances of finding HLA compatible donors in a large sample from Brazil, a highly admixed country. We query REDOME, Brazil's Bone Marrow Registry, and investigate how different criteria for identifying ancestry influence the chances of finding a match. We find that individuals who self-identify as "Black" and "Mixed" on average have lower chances of finding matches than those who self-identify as "White" (up to 57% reduction). We next show that an individual's African genetic ancestry, estimated using molecular markers and quantified as the proportion of an individual's genome that traces its ancestry to Africa, is strongly associated with reduced chances of finding a match (up to 60% reduction). Finally, we document that the strongest reduction in chances of finding a match is associated with having an MHC region of exclusively African ancestry (up to 75% reduction). We apply our findings to a specific condition, for which there is a clinical indication for transplantation: sickle-cell disease. We show that the increased African ancestry in patients with this disease leads to reduced chances of finding a match, when compared to the remainder of the sample, without the condition. Our results underscore the influence of ancestry on chances of finding compatible HLA matches, and indicate that efforts guided to increasing the African component of registries are necessary.
MeSH term(s)	Anemia, Sickle Cell/genetics ; Black People/genetics ; Bone Marrow/surgery ; Bone Marrow Transplantation/methods ; Brazil ; Ethnicity/genetics ; Gene Frequency/genetics ; Genotype ; HLA Antigens/genetics ; Hematopoietic Stem Cell Transplantation/methods ; Histocompatibility Testing/methods ; Humans ; Polymorphism, Genetic/genetics ; Registries ; Unrelated Donors ; White People/genetics
Chemical Substances	HLA Antigens
Language	English
Publishing date	2020-11-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.584950
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Article ; Online: Biogeographical ancestry is associated with socioenvironmental conditions and infections in a Latin American urban population

Thiago Magalhães da Silva / Rosemeire L. Fiaccone / Fernanda S.G. Kehdy / Eduardo Tarazona-Santos / Laura C. Rodrigues / Gustavo N.O. Costa / Camila A. Figueiredo / Neuza Maria Alcantara-Neves / Maurício L. Barreto

SSM: Population Health, Vol 4, Iss , Pp 301-

2018 Volume 306

Abstract: ... to the children’s guardians to evaluate socioenvironmental conditions. Infection (or pathogen exposure) was ...

Abstract	Racial inequalities are observed for different diseases and are mainly caused by differences in socioeconomic status between ethnoracial groups. Genetic factors have also been implicated, and recently, several studies have investigated the association between biogeographical ancestry (BGA) and complex diseases. However, the role of BGA as a proxy for non-genetic health determinants has been little investigated. Similarly, studies comparing the association of BGA and self-reported skin colour with these determinants are scarce. Here, we report the association of BGA and self-reported skin colour with socioenvironmental conditions and infections. We studied 1246 children living in a Brazilian urban poor area. The BGA was estimated using 370,539 genome-wide autosomal markers. Standardised questionnaires were administered to the children’s guardians to evaluate socioenvironmental conditions. Infection (or pathogen exposure) was defined by the presence of positive serologic test results for IgG to seven pathogens (Toxocara spp, Toxoplasma gondii, Helicobacter pylori, and hepatitis A, herpes simplex, herpes zoster and Epstein-Barr viruses) and the presence of intestinal helminth eggs in stool samples (Ascaris lumbricoides and Trichiuris trichiura). African ancestry was negatively associated with maternal education and household income and positively associated with infections and variables, indicating poorer housing and living conditions. The self-reported skin colour was associated with infections only. In stratified analyses, the proportion of African ancestry was associated with most of the outcomes investigated, particularly among admixed individuals. In conclusion, BGA was associated with socioenvironmental conditions and infections even in a low-income and highly admixed population, capturing differences that self-reported skin colour miss. Importantly, our findings suggest caution in interpreting significant associations between BGA and diseases as indicative of the genetic factors involved. Keywords: ...
Keywords	Public aspects of medicine ; RA1-1270 ; Social sciences (General) ; H1-99
Language	English
Publishing date	2018-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: African biogeographical ancestry, atopic and non-atopic asthma and atopy: A study in Latin American children.

da Silva, Thiago M / Fiaccone, Rosemeire L / Kehdy, Fernanda S G / Tarazona-Santos, Eduardo / Rodrigues, Laura C / Costa, Gustavo N O / Figueiredo, Camila A / Dos Santos, Darci N / Feitosa, Caroline A / Fattore, Gisel L / Santos, Leticia M / Alcantara-Neves, Neuza M / Cruz, Álvaro A / Barreto, Maurício L

Pediatric pulmonology

2018 Volume 54, Issue 2, Page(s) 125–132

Abstract: Background: Genetic variants underlying African ancestry have been suggested be implicated in the ethnic-racial inequalities reported for asthma and allergies.: Objectives: To investigate the association between individual African ancestry and asthma ...

Abstract	Background: Genetic variants underlying African ancestry have been suggested be implicated in the ethnic-racial inequalities reported for asthma and allergies. Objectives: To investigate the association between individual African ancestry and asthma symptoms, atopic and non-atopic asthma, and atopy in children. Methods: A cross-sectional study encompassing 1190 individuals was conducted. African biogeographic ancestry was estimated using 370 539 genome-wide SNPs. Serum levels of specific IgE were measured, and skin prick test (SPT) performed for the most common local aeroallergens. Information on asthma symptoms was obtained by applying the International Study of Allergy and Asthma in Childhood questionnaire. The associations between the proportion of individual African ancestry and the outcomes investigated were analyzed through multivariate models adjusted for socio-environmental variables, infections markers, and psychosocial factors. Results: Each 20% increase in the proportion of African ancestry was negatively associated with SPT reactivity (OR: 0.79, 95%CI: 0.66-0.96) and positively associated with asthma symptoms in non-atopic individuals (OR: 1.40, 95%CI: 1.03-1.89). We estimated that socioeconomic status and number of infections mediated 28.4% of the effect of African ancestry on SPT reactivity, while 20.2% of the effect on non-atopic asthma was explained by socioeconomic status and behavioral problems in children. Conclusions: The negative association observed between African ancestry and atopy is most probably explained by unobserved environmental or social factors that covariate with ancestry. For non-atopic asthma, in turn, putative genetic variants of risk underlying African ancestry may play some role.
MeSH term(s)	African Continental Ancestry Group/genetics ; Allergens/immunology ; Asthma/blood ; Asthma/genetics ; Asthma/immunology ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Humans ; Hypersensitivity, Immediate/blood ; Hypersensitivity, Immediate/genetics ; Hypersensitivity, Immediate/immunology ; Immunoglobulin E/blood ; Infant ; Infant, Newborn ; Latin America ; Male ; Polymorphism, Single Nucleotide ; Skin Tests
Chemical Substances	Allergens ; Immunoglobulin E (37341-29-0)
Language	English
Publishing date	2018-12-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632784-9
ISSN	1099-0496 ; 8755-6863
ISSN (online)	1099-0496
ISSN	8755-6863
DOI	10.1002/ppul.24213
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