Genetic Ancestry and Self-Reported "Skin Color/Race" in the Urban Admixed Population of São Paulo City, Brazil.

Epidemiological studies frequently classify groups based on phenotypes like self-reported skin color/race, which inaccurately represent genetic ancestry and may lead to misclassification, particularly among individuals of multiracial backgrounds. This study aimed to characterize both global and local genome-wide genetic ancestries and to assess their relationship with self-reported skin color/race in an admixed population of Sao Paulo city. We analyzed 226,346 single-nucleotide polymorphisms from 841 individuals participating in the population-based ISA-Nutrition study. Our findings confirmed the admixed nature of the population, demonstrating substantial European, significant Sub-Saharan African, and minor Native American ancestries, irrespective of skin color. A correlation was observed between global genetic ancestry and self-reported color-race, which was more evident in the extreme proportions of African and European ancestries. Individuals with higher African ancestry tended to identify as Black, those with higher European ancestry tended to identify as White, and individuals with higher Native American ancestry were more likely to self-identify as Mixed, a group with diverse ancestral compositions. However, at the individual level, this correlation was notably weak, and no deviations were observed for specific regions throughout the individual's genome. Our findings emphasize the significance of accurately defining and thoroughly analyzing race and ancestry, especially within admixed populations.

Genome-Wide Admixture and Association Study of Serum Selenium Deficiency to Identify Genetic Variants Indirectly Linked to Selenium Regulation in Brazilian Adults.

Blood selenium (Se) concentrations differ substantially by population and could be influenced by genetic variants, increasing Se deficiency-related diseases. We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with serum Se deficiency in 382 adults with admixed ancestry. Genotyping arrays were combined to yield 90,937 SNPs. R packages were applied to quality control and imputation. We also performed the ancestral proportion analysis. The Search Tool for the Retrieval of Interacting Genes was used to interrogate known protein-protein interaction networks (PPIs). Our ancestral proportion analysis estimated 71% of the genome was from Caucasians, 22% was from Africans, and 8% was from East Asians. We identified the SNP rs1561573 in the TraB domain containing 2B (TRABD2B), rs425664 in MAF bZIP transcription factor (MAF), rs10444656 in spermatogenesis-associated 13 (SPATA13), and rs6592284 in heat shock protein nuclear import factor (HIKESHI) genes. The PPI analysis showed functional associations of Se deficiency, thyroid hormone metabolism, NRF2-ARE and the Wnt pathway, and heat stress. Our findings show evidence of a genetic association between Se deficiency and metabolic pathways indirectly linked to Se regulation, reinforcing the complex relationship between Se intake and the endogenous factors affecting the Se requirements for optimal health.

Genetic ancestry is related to potential sources of breast cancer health disparities among Colombian women.

Breast cancer health disparities are linked to clinical-pathological determinants, socioeconomic inequities, and biological factors such as genetic ancestry. These factors collectively interact in complex ways, influencing disease behavior, especially among highly admixed populations like Colombians. In this study, we assessed contributing factors to breast cancer health disparities according to genetic ancestry in Colombian patients from a national cancer reference center. We collected non-tumoral paraffin embedded (FFPE) blocks from 361 women diagnosed with breast cancer at the National Cancer Institute (NCI) to estimate genetic ancestry using a 106-ancestry informative marker (AIM) panel. Differences in European, Indigenous American (IA) and African ancestry fractions were analyzed according to potential sources of breast cancer health disparities, like etiology, tumor-biology, treatment administration, and socioeconomic-related factors using a Kruskal-Wallis test. Our analysis revealed a significantly higher IA ancestry among overweight patients with larger tumors and those covered by a subsidized health insurance. Conversely, we found a significantly higher European ancestry among patients with smaller tumors, residing in middle-income households, and affiliated to the contributory health regime, whereas a higher median of African ancestry was observed among patients with either a clinical, pathological, or stable response to neoadjuvant treatment. Altogether, our results suggest that the genetic legacy among Colombian patients, measured as genetic ancestry fractions, may be reflected in many of the clinical-pathological variables and socioeconomic factors that end up contributing to health disparities for this disease.

Performance of polygenic risk scores for cancer prediction in a racially diverse academic biobank.

PURPOSE: Genome-wide association studies have identified hundreds of single nucleotide variations (formerly single nucleotide polymorphisms) associated with several cancers, but the predictive ability of polygenic risk scores (PRSs) is unclear, especially among non-Whites. METHODS: PRSs were derived from genome-wide significant single-nucleotide variations for 15 cancers in 20,079 individuals in an academic biobank. We evaluated the improvement in discriminatory accuracy by including cancer-specific PRS in patients of genetically-determined African and European ancestry. RESULTS: Among the individuals of European genetic ancestry, PRSs for breast, colon, melanoma, and prostate were significantly associated with their respective cancers. Among the individuals of African genetic ancestry, PRSs for breast, colon, prostate, and thyroid were significantly associated with their respective cancers. The area under the curve of the model consisting of age, sex, and principal components was 0.621 to 0.710, and it increased by 1% to 4% with the inclusion of PRS in individuals of European genetic ancestry. In individuals of African genetic ancestry, area under the curve was overall higher in the model without the PRS (0.723-0.810) but increased by <1% with the inclusion of PRS for most cancers. CONCLUSION: PRS moderately increased the ability to discriminate the cancer status in individuals of European but not African ancestry. Further large-scale studies are needed to identify ancestry-specific genetic factors in non-White populations to incorporate PRS into cancer risk assessment.

Genetic ancestry, admixture, and population structure in rural Dominica.

The Caribbean is a genetically diverse region with heterogeneous admixture compositions influenced by local island ecologies, migrations, colonial conflicts, and demographic histories. The Commonwealth of Dominica is a mountainous island in the Lesser Antilles historically known to harbor communities with unique patterns of migration, mixture, and isolation. This community-based population genetic study adds biological evidence to inform post-colonial narrative histories in a Dominican horticultural village. High density single nucleotide polymorphism data paired with a previously compiled genealogy provide the first genome-wide insights on genetic ancestry and population structure in Dominica. We assessed family-based clustering, inferred global ancestry, and dated recent admixture by implementing the fastSTRUCTURE clustering algorithm, modeling graph-based migration with TreeMix, assessing patterns of linkage disequilibrium decay with ALDER, and visualizing data from Dominica with Human Genome Diversity Panel references. These analyses distinguish family-based genetic structure from variation in African, European, and indigenous Amerindian admixture proportions, and analyses of linkage disequilibrium decay estimate admixture dates 5-6 generations (~160 years) ago. African ancestry accounts for the largest mixture components, followed by European and then indigenous components; however, our global ancestry inferences are consistent with previous mitochondrial, Y chromosome, and ancestry marker data from Dominica that show uniquely higher proportions of indigenous ancestry and lower proportions of African ancestry relative to known admixture in other French- and English-speaking Caribbean islands. Our genetic results support local narratives about the community's history and founding, which indicate that newly emancipated people settled in the steep, dense vegetation along Dominica's eastern coast in the mid-19th century. Strong genetic signals of post-colonial admixture and family-based structure highlight the localized impacts of colonial forces and island ecologies in this region, and more data from other groups are needed to more broadly inform on Dominica's complex history and present diversity.

The Mitochondrial DNA Landscape of Modern Mexico.

Mexico is a rich source for anthropological and population genetic studies with high diversity in ethnic and linguistic groups. The country witnessed the rise and fall of major civilizations, including the Maya and Aztec, but resulting from European colonization, the population landscape has dramatically changed. Today, the majority of Mexicans do not identify themselves as Indigenous but as admixed, and appear to have very little in common with their pre-Columbian predecessors. However, when the maternally inherited mitochondrial (mt)DNA is investigated in the modern Mexican population, this is not the case. Control region sequences of 2021 samples deriving from all over the country revealed an overwhelming Indigenous American legacy, with almost 90% of mtDNAs belonging to the four major pan-American haplogroups A2, B2, C1, and D1. This finding supports a very low European contribution to the Mexican gene pool by female colonizers and confirms the effectiveness of employing uniparental markers as a tool to reconstruct a country's history. In addition, the distinct frequency and dispersal patterns of Indigenous American and West Eurasian clades highlight the benefit such large and country-wide databases provide for studying the impact of colonialism from a female perspective and population stratification. The importance of geographical database subsets not only for forensic application is clearly demonstrated.

High-Resolution Characterization of KIR Genes in a Large North American Cohort Reveals Novel Details of Structural and Sequence Diversity.

The KIR (killer-cell immunoglobulin-like receptor) region is characterized by structural variation and high sequence similarity among genes, imposing technical difficulties for analysis. We undertook the most comprehensive study to date of KIR genetic diversity in a large population sample, applying next-generation sequencing in 2,130 United States European-descendant individuals. Data were analyzed using our custom bioinformatics pipeline specifically designed to address technical obstacles in determining KIR genotypes. Precise gene copy number determination allowed us to identify a set of uncommon gene-content KIR haplotypes accounting for 5.2% of structural variation. In this cohort, KIR2DL4 is the framework gene that most varies in copy number (6.5% of all individuals). We identified phased high-resolution alleles in large multi-locus insertions and also likely founder haplotypes from which they were deleted. Additionally, we observed 250 alleles at 5-digit resolution, of which 90 have frequencies ≥1%. We found sequence patterns that were consistent with the presence of novel alleles in 398 (18.7%) individuals and contextualized multiple orphan dbSNPs within the KIR complex. We also identified a novel KIR2DL1 variant, Pro151Arg, and demonstrated by molecular dynamics that this substitution is predicted to affect interaction with HLA-C. No previous studies have fully explored the full range of structural and sequence variation of KIR as we present here. We demonstrate that pairing high-throughput sequencing with state-of-art computational tools in a large cohort permits exploration of all aspects of KIR variation including determination of population-level haplotype diversity, improving understanding of the KIR system, and providing an important reference for future studies.

Novel loci and Mapuche genetic ancestry are associated with pubertal growth traits in Chilean boys.

Puberty is a complex developmental process that varies considerably among individuals and populations. Genetic factors explain a large proportion of the variability of several pubertal traits. Recent genome-wide association studies (GWAS) have identified hundreds of variants involved in traits that result from body growth, like adult height. However, they do not capture many genetic loci involved in growth changes over distinct growth phases. Further, such GWAS have been mostly performed in Europeans, but it is unknown how these findings relate to other continental populations. In this study, we analyzed the genetic basis of three pubertal traits; namely, peak height velocity (PV), age at PV (APV) and height at APV (HAPV). We analyzed a cohort of 904 admixed Chilean children and adolescents with European and Mapuche Native American ancestries. Height was measured on roughly a [Formula: see text]month basis from childhood to adolescence between 2006 and 2019. We predict that, in average, HAPV is 4.3 cm higher in European than in Mapuche adolescents (P = 0.042), and APV is 0.73 years later in European compared with Mapuche adolescents (P = 0.023). Further, by performing a GWAS on 774, 433 single-nucleotide polymorphisms, we identified a genetic signal harboring 3 linked variants significantly associated with PV in boys (P [Formula: see text]). This signal has never been associated with growth-related traits.

Ancestral genetic legacy of the extant population of Argentina as predicted by autosomal and X-chromosomal DIPs.

Aiming to determine their ancestry diagnostic potential, we selected two sets of nuclear deletion/insertion polymorphisms (DIPs), including 30 located on autosomal chromosomes and 33 on the X chromosome. We analysed over 200 unrelated Argentinean individuals living in urban areas of Argentina. As in most American countries, the extant Argentinean population is the result of tricontinental genetic admixture. The peopling process within the continent was characterised by mating bias involving Native American and enslaved African females and European males. Differential results were detected between autosomal DIPs and X-DIPs. The former showed that the European component was the largest (77.8%), followed by the Native American (17.9%) and African (4.2%) components, in good agreement with the previously published results. In contrast, X-DIPs showed that the European genetic contribution was also predominant but much smaller (52.9%) and considerably larger Native American and African contributions (39.6% and 7.5%, respectively). Genetic analysis revealed continental genetic contributions whose associated phenotypic traits have been mostly lost. The observed differences between the estimated continental genetic contribution proportions based on autosomal DIPs and X-DIPs reflect the effects of autosome and X-chromosome transmission behaviour and their different recombination patterns. This work shows the ability of the tested DIP panels to infer ancestry and confirm mating bias. To the best of our knowledge, this is the first study focusing on ancestry-informative autosomal DIP and X-DIP comparisons performed in a sample representing the entire Argentinean population.

Genetic diversity, structure, and admixture in Mayans from Guatemala and Mexico based on 15 short tandem repeats.

OBJECTIVE: To analyze the genetic origin, relationships, structure, and admixture in Mayan Native American groups from Guatemala and Mexico based on 15 autosomal short tandem repeats (STRs) loci commonly used in human identification (HID). METHODS: We genotyped 513 unrelated Mayan samples from Guatemala based on 15 STR loci (AmpFlSTR® Identifiler kit). Moreover, we included 4408 genotypes previously reported, as following: Mayas from Guatemala and Mexico (n = 1666) and from Latin American, European, and African (n = 2742) populations. Forensic parameters, genetic distances, admixture, and population structure were assessed. RESULTS: Forensic parameters of the 15 STRs in different Mayan groups from Guatemala were reported. Low (Fst = 0.78%; p = 0.000) and non-significant differentiation (Fst = 1.8%; p = 0.108) were observed in Mayas from Guatemala and Mexico, respectively. The relative homogeneity observed among Mayan groups supported theories of extensive pre-Columbian gene flow and trade throughout the Mayan Empire. The distribution of the three Native American ancestries among these Mayan groups did not support the presumable Guatemalan origin of Tojolabal and Lacandon people (South, Mexico). The nonsignificant differentiation between Ladinos and Mayas suggests a relative panmixia in Guatemala. Mestizos from southeastern Mexico and Guatemala constitute a core of Native American ancestry in Latin America related to the Mayan Empire in Central America. CONCLUSIONS: The higher European admixture and homogeneity in Mexican Mayas of the Yucatan Peninsula suggest more intensive post-Columbian gene flow in this region than in Guatemalan Mayas.

Polymorphism of the bradykinin type 2 receptor gene modulates blood pressure profile and microvascular function in prepubescent children.

Previous reports reveal that +9/-9 polymorphism of the bradykinin B2 receptor (BDKRB2) is suggestive of cardiometabolic diseases. The aim of this study was to examine the impact of BDKRB2 + 9/-9 polymorphism genotypes on the blood pressure parameters and microvascular function in prepubescent children. We screened for BDKRB2 + 9/-9 polymorphism in the DNA of 145 children (86 boys and 59 girls), and its association with body composition, blood pressure levels, biochemical parameters, and endothelial function was determined. No significant association of the BDKRB2 genotypes with gender (P=0.377), race (P=0.949) or family history of cardiovascular disease (CVD) (P=0.858) was observed. Moreover, we did not identify any interaction between BDKRB2 genotypes with a phenotype of obesity (P=0.144). Children carrying the +9/+9 genotype exhibited a significant linear trend with higher levels of systolic blood pressure and pulse pressure (P<0.001). Moreover, the presence of +9 allele resulted in a decrease of reactive hyperemia index, showing a decreasing linear trend from -9/-9 to +9/+9, wherein this parameter of endothelial function was the lowest in the +9/+9 children, intermediate in the +9/-9 children, and the highest in the -9/-9 children (P<0.001). There was a significant inverse correlation between reactive hyperemia index and systolic blood pressure (r= - 0.348, P< 0.001) and pulse pressure (r= - 0.399, P< 0.001). Our findings indicate that the +9/+9 BDKRB2 genotype was associated with high blood pressure and microvascular dysfunction in prepubescent Brazilian children.

Neuromyelitis optica is an HLA associated disease different from Multiple Sclerosis: a systematic review with meta-analysis.

Neuromyelitis Optica and Multiple Sclerosis are idiopathic inflammatory demyelinating diseases of the central nervous system that currently are considered distinct autoimmune diseases, so differences in genetic susceptibility would be expected. This study aimed to investigate the HLA association with Neuromyelitis Optica by a systematic review with meta-analysis. The STROBE instrument guided research paper assessments. Thirteen papers published between 2009 and 2020 were eligible. 568 Neuromyelitis Optica patients, 41.4% Asians, 32.4% Latin Americans and 26.2% Europeans were analyzed. Only alleles of the DRB1 locus were genotyped in all studies. Neuromyelitis Optica patients have 2.46 more chances of having the DRB1*03 allelic group than controls. Ethnicity can influence genetic susceptibility. The main HLA association with Neuromyelitis Optica was the DRB1*03:01 allele in Western populations and with the DPB1*05:01 allele in Asia. Differences in the Multiple Sclerosis and Neuromyelitis Optica genetic susceptibility was confirmed in Afro descendants. The DRB1*03 allelic group associated with Neuromyelitis Optica has also been described in other systemic autoimmune diseases.

Population impact of pharmacogenetic tests in admixed populations across the Americas.

The current population of the Americas (~1 billion people) is highly heterogeneous as a result of five centuries of admixture between three major parental populations, namely Native Amerindians, Europeans, and subSaharan Africans. This heterogeneity has important pharmacogenetic (PGx) implications. The present study explores this issue with respect to the population impact of PGx tests listed in the CPIC and DWPG guidelines for the cancer chemotherapeutic agents fluoropyrimidines, irinotecan, and thiopurines. Population impact was assessed by the number of individuals needed to genotype (NNG) and to treat [NNT] in order to prevent one additional adverse effect. The 1000 Genomes Project database was accessed to obtain genotypes for the relevant PGx markers and to estimate individual proportions of Native, European, and African ancestry for six recently admixed populations across the Americas. The ancestry proportions were then employed to devise three sub-cohorts, denoted NAT, EUR, and AFR, in which one of the three major ancestral roots predominates largely (8 to 30-fold) over the other two. Minor allele frequency (MAF) of NUDT15 rs116855232, TPMT rs1800460, and UGT1A1 rs887829 differed significantly across the three sub-cohorts, whereas no difference was observed for TPMT rs1142345 and 1800462, and the four DPYD variants interrogated. The frequency of combined TPMT/NUDT and UGT1A1, but not DPD, metabolic phenotypes differed significantly among the sub-cohorts. The NNGs for the drug/sub-cohorts pairs, ranged from 12 (irinotecan/UGT1A1 in EUR) to 360 (fluoropyrimidines/DPYD in NAT). Differences in MAF of the interrogated variants and consequently in the distribution of metabolic phenotypes, plus the variable individual proportions of biogeographical ancestry concur to the 30-fold range of NNGs for the PGx tests, across the sub-cohorts. This large variation is likely to influence the perceived benefits and the clinical adoption of PGx screening for the chemotherapeutic agents investigated. This is of especial concern for fluoropyrimidines, in view of the large NNGs observed in the study sub-cohorts (NNG = 176-360) and confirmed in cancer patients from Brazil (NNG = 312).

Genomic ancestry and metabolic syndrome in individuals with type 1 diabetes from an admixed population: a multicentre, cross-sectional study in Brazil.

AIMS: To evaluate the relationship between self-reported colour-race, genomic ancestry, and metabolic syndrome in an admixed Brazilian population with type 1 diabetes. METHODS: We included 1640 participants with type 1 diabetes. The proportions of European, African and Amerindian genomic ancestries were determined by 46 ancestry informative markers of insertion deletion. Two different sets of analyses were performed to determine whether self-reported colour-race and genomic ancestry were predictors of metabolic syndrome. RESULTS: Metabolic syndrome was identified in 29.8% of participants. In the first model, the factors associated with metabolic syndrome were: female gender (odds ratio 1.95, P < 0.001); diabetes duration (odds ratio 1.04, P < 0.001); family history of type 2 diabetes (odds ratio 1.36, P = 0.019); and acanthosis nigricans (odds ratio 5.93, P < 0.001). Colour-race was not a predictive factor for metabolic syndrome. In the second model, colour-race was replaced by European genomic ancestry. The associated factors were: female gender (odds ratio 1.95, P < 0.001); diabetes duration (odds ratio 1.04, P < 0.001); family history of type 2 diabetes (odds ratio 1.39, P = 0.011); and acanthosis nigricans (odds ratio 6.12, P < 0.001). Physical exercise (≥3 times a week) was a protective factor (odds ratio 0.77, P = 0.041), and European genomic ancestry was not associated with metabolic syndrome but showed an odds ratio of 1.77 (P = 0.05). CONCLUSIONS: Although a higher level of European genomic ancestry was observed among participants with metabolic syndrome in the univariate analysis, this association did not persist after multivariable adjustments. Further prospective studies in other highly admixed populations remain necessary to better evaluate whether the European ancestral component modulates the development of metabolic syndrome in type 1 diabetes.

"Distribution of paternal lineages in Mestizo populations throughout Mexico: an in silico study based on Y-STR haplotypes".

The Mexican-Mestizo population arose following European contact with the Americas due to the admixture of principally Spaniards, Native Americans, and Africans around 500 years ago. Because the paternal lineage distribution of the Mexican population has been poorly investigated, this study inferred the haplogroups of ten populations based on 1859 haplotypes (Y-STR data) using two haplogroup predictor programs. In the Mexican population sample, we found predominantly European ancestry (50.1%), followed by Native American (32.5%), Eurasian (13.4%), African (2.1%), East African-South Eurasian (1.3%), and Asian (0.6%) ancestries. In general, our results support a contrary north-to-south gradient throughout the Mexican territory of European and Native-American ancestries, respectively. Moreover, the presence of West-European R1b and Sub-Saharan African E1b1a haplogroups agrees with historical and genetic data of gene flow during the European conquest. This study represents the effort to analyze these paternal lineages on a large scale by taking advantage of Y-STR haplotype data to determine the distribution and ancestry proportions in this country.

Inhibitory KIR2DL2 Gene: Risk for Deep Endometriosis in Euro-descendants.

Endometriosis (EDT) is an inflammatory disease characterized by implantation/growth of endometrial tissue, glands, and/or stroma, outside the uterus. Reduced NK cell cytotoxic activity has been implicated in its pathogenesis, together with other immunologic alterations. We investigated the influence of KIR gene polymorphisms and their HLA ligand combinations in deep endometriosis (DE) susceptibility. One hundred sixty women with a histological diagnosis of DE and 202 control women without the disease, who underwent laparoscopy, were enrolled. The DE group was subdivided into initial (I/II; n = 60) and advanced stages (III/IV, n = 100). KIR and HLA class I gene polymorphisms were typed by PCR-SSP and sequence-based-typing (SBT), respectively. We observed a significant association of KIR2DL2, an inhibitory gene of B haplotype, conferring risk for DE in Euro-descendants. Positive associations of Bx haplotype and centromeric AB segments were also found. However, no association with KIR-HLA ligand combination was observed. Our data suggest KIR2DL2 gene to be a relevant factor favoring NK inhibition in DE in Euro-descendants, contributing to the defective NK cytotoxic activity and impaired clearance of ectopic endometrial cells in the disease.

How Ancestry Influences the Chances of Finding Unrelated Donors: An Investigation in Admixed Brazilians.

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.

Genetic admixture in Brazil.

We review studies from our laboratories using different molecular tools to characterize the Amerindian, European and African ancestry of Brazilians. Initially we used uniparental DNA markers to investigate the contribution of distinct Y chromosome and mitochondrial DNA lineages to present-day populations. High levels of genetic admixture and strong directional mating between European males and Amerindian and African females were unraveled. We next analyzed different types of biparental autosomal polymorphisms. Especially useful was a set of 40 insertion-deletion polymorphisms (indels) that when studied worldwide proved exquisitely sensitive in discriminating between Amerindians, Europeans and Sub-Saharan Africans. When applied to the study of Brazilians these markers confirmed extensive genomic admixture. We then studied ancestry differences in different regions by statistically controlling them to eliminate color considerations. The European ancestry was predominant in all regions studied, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of 6 million Europeans to Brazil in the 19th and 20th centuries is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. Brazilians should be assessed individually, as 210 million human beings, and not as members of specific regions or color groups.

Association of the 5HTTLPR Polymorphism with Obesity in Mexican Women with High Native American Ancestry.

Aims: The 5HTT gene has been associated with obesity; this study aimed to determine the association between L- and S-alleles at the 5HTTLPR polymorphism with obesity in indigenous Mexican populations. Materials and Methods: A total of 362 individuals, 289 belonging to eight Native American (NA) groups; 40 Mexican mestizos; and 33 Caucasian Mennonites were enrolled in a cross-sectional study. High (≥90%) and low (<90%) NA ancestry was molecularly determined. A body mass index >30 kg/m2 was considered as obese. The L- and S-alleles of the 5HTTLPR locus were identified by PCR; the association between alleles and obesity was performed by logistic regression analysis. Results: A significantly lower prevalence of obesity (35%) was observed in participants from communities with high NA ancestry (p < 0.005). Under a dominant heritance model the L-allele was associated with obesity in women with high NA ancestry (odds ratio [OR] 7.27; 95% confidence interval [CI] 1.6-32.5; p = 0.009) but not in women with low NA ancestry (OR 0.83; 95% CI 0.3-2.2; p = 0.71); no association was observed in men. Conclusion: Our results suggest that the 5HTTLPR L-allele is a risk factor for developing obesity in Mexican women with high NA ancestry (≥90%).

Genomic Regions 10q22.2, 17q21.31, and 2p23.1 Can Contribute to a Lower Lung Function in African Descent Populations.

Accumulated evidence supports the contribution of genetic factors in modulating airway function, especially ancestry. We investigated whether genetic polymorphisms can affect lung function in a mixed Brazilian child population using the admixture mapping strategy through RFMix software version 1.5.4 (Stanford University, Stanford, CA, USA), followed by fine mapping, to identify regions whereby local African or European ancestry is associated with lung function measured by the forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) ratio, an indicator of airway obstruction. The research cohort included 958 individuals aged 4 to 11 years enrolled in the SCAALA (Social Change, Asthma, Allergy in Latin America) Program. We identified that African ancestry at 17q21.31, 10q22.2, and 2p23.1 regions was associated with lower lung function measured by FEV1/FVC p < 1.9 × 10-4. In contrast, European ancestry at 17q21.31 showed an opposite effect. Fine mapping pointed out 5 single nucleotide polymorphisms (SNPs) also associated in our replication cohort (rs10999948, rs373831475, rs8068257, rs6744555, and rs1520322). Our results suggest that genomic regions associated with ancestry may contribute to differences in lung function measurements in African American children in Brazil replicated in a cohort of Brazilian adults. The analysis strategy used in this work is especially important for phenotypes, such as lung function, which has considerable disparities in terms of measurements across different populations.