Proportion Of Native American Ancestry Research Articles

Variability of the SNP rs9939609 in the FTO Gene and Ancestry in Latin American Populations

Introduction: Obesity is a complex condition influenced by genetic and environmental factors. The FTO gene has been associated with obesity through several single nucleotide polymorphisms (SNPs), particularly rs9939609, related to higher body mass index (BMI) and risk of obesity. FTO variants influence the regulation of appetite and energy metabolism by affecting RNA methylation and the expression of key genes in adipogenesis.Objective: To investigate the association between the FTO rs9939609 SNP and genetic ancestry proportions in Latin American populations.Methods: Genotypes for rs9939609 were obtained using VcfTools and the 1000 Genomes Project database. Samples from Latin America were selected, covering four mixed populations: Colombians (n=94), Mexicans (n=64), Peruvians (n=85) and Puerto Ricans (n=104), totaling 347 individuals. To estimate genetic ancestry proportions, 446 SNPs from a panel of ancestry informative markers (AIMs) were used.Results: Individuals with the AA genotype of SNP rs9939609 have a higher proportion of Native American ancestry and a lower proportion of European ancestry compared to TT and AT genotypes. The variability in the proportions of ancestry according to the genotype of the SNP rs9939609 suggests a possible genetic stratification in the Latin American populations studied.Conclusions: These findings highlight the importance of considering ancestral composition in genetic studies related to obesity. More research is needed to understand how gene-environment interactions contribute to obesity in various populations, which could lead to more effective and targeted intervention strategies

Amerindian ancestry proportion as a risk factor for inflammatory bowel diseases: results from a Latin American Andean cohort.

Latin American populations remain underrepresented in genetic studies of inflammatory bowel diseases (IBDs). Most genetic association studies of IBD rely on Caucasian, African, and Asian individuals. These associations have yet to be evaluated in detail in the Andean region of South America. We explored the contribution of IBD-reported genetic risk variants to a Chilean cohort and the ancestry contribution to IBD in this cohort. A total of 192 Chilean IBD patients were genotyped using Illumina's Global Screening Array. Genotype data were combined with similar information from 3,147 Chilean controls. The proportions of Aymara, African, European, and Mapuche ancestries were estimated using the software ADMIXTURE. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for gender, age, and ancestry proportions. We also explored associations with previously reported IBD-risk variants independently and in conjunction with genetic ancestry. The first and third quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7 and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52-3.48) for the lowest vs. the highest group. Only one variant (rs7210086) of the 180 reported IBD-risk SNPs was associated with IBD risk in the Chilean cohort (adjusted P = 0.01). This variant is related to myeloid cells. The type and proportion of Native American ancestry in Chileans seem to be associated with IBD risk. Variants associated with IBD risk in this Andean region were related to myeloid cells and the innate immune response.

Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers

BackgroundLatin American and Hispanic women are less likely to develop breast cancer (BC) than women of European descent. Observational studies have found an inverse relationship between the individual proportion of Native American ancestry and BC risk. Here, we use ancestry-informative markers to rule out potential confounding of this relationship, estimating the confounder-free effect of Native American ancestry on BC risk.Methods and study populationWe used the informativeness for assignment measure to select robust instrumental variables for the individual proportion of Native American ancestry. We then conducted separate Mendelian randomization (MR) analyses based on 1401 Colombian women, most of them from the central Andean regions of Cundinamarca and Huila, and 1366 Mexican women from Mexico City, Monterrey and Veracruz, supplemented by sensitivity and stratified analyses.ResultsThe proportion of Colombian Native American ancestry showed a putatively causal protective effect on BC risk (inverse variance-weighted odds ratio [OR] = 0.974 per 1% increase in ancestry proportion, 95% confidence interval [CI] 0.970–0.978, p = 3.1 × 10–40). The corresponding OR for Mexican Native American ancestry was 0.988 (95% CI 0.987–0.990, p = 1.4 × 10–44). Stratified analyses revealed a stronger association between Native American ancestry and familial BC (Colombian women: OR = 0.958, 95% CI 0.952–0.964; Mexican women: OR = 0.973, 95% CI 0.969–0.978), and stronger protective effects on oestrogen receptor (ER)-positive BC than on ER-negative and triple-negative BC.ConclusionsThe present results point to an unconfounded protective effect of Native American ancestry on BC risk in both Colombian and Mexican women which appears to be stronger for familial and ER-positive BC. These findings provide a rationale for personalised prevention programmes that take genetic ancestry into account, as well as for future admixture mapping studies.

1091-P: Genetic Ancestry Influences Metformin Treatment Response in Youth with Type 2 Diabetes

In youth with type 2 diabetes (T2D), glycemic response to metformin varies by racial and ethnic group. In the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study metformin failure rates were lower in non-Hispanic White (NHW) youth by self-report compared with non-Hispanic Black (NHB) and Hispanic youth. Understanding and addressing the mechanisms for differences in response are critical to reducing health disparities. We aimed to examine the association between genetic ancestry and risk for metformin treatment failure and evaluate whether individual global ancestry proportions predict metformin response in TODAY participants. Global ancestry proportions were estimated using FastStructure. Cox-proportional hazards analysis with genetic ancestry as a covariate was performed with the primary outcome the need for insulin or A1C ≥ 8%. Age, sex, BMI Z score, baseline A1C, and treatment arms were the other covariates. After quality control, 506 participants of mean age 14±2 y, 65% female, mean BMI Z score 2.2±0.5 kg/m2 and mean baseline A1C 6.0±0.7% were analyzed. Similar to by self-report, when stratified by genetic ancestry NHB youth had significantly higher treatment failure rates compared with other groups (P=0.02). The proportion of European ancestry in self-reported ethnic strata of admixed participants was associated with improved metformin response in the NHB (n=185) and Hispanic (n=208) groups (HR 0.4, 95% CI 0.16-0.98, P=0.04). Proportion of Native American ancestry was associated with worse response (HR 1.5, 95% CI 1.02-2.2, P=0.04) across all participants and associations with proportion African ancestry were not significant. In sum, genetic ancestry influences metformin response with greater proportion of European and Native American ancestry associated with improved and worse glycemic response respectively in TODAY. These differences could be related to biological, social or cultural factors and should be examined to reduce health disparities in T2D. Disclosure S.Srinivasan: None. T.I.Pollin: None. A.Manning: None. J.C.Florez: Consultant; AstraZeneca, Novo Nordisk, Other Relationship; AstraZeneca, Merck & Co., Inc. L.Chen: None. M.M.Kelsey: Other Relationship; Boehringer Ingelheim Inc., Janssen Pharmaceuticals, Inc., Rhythm Pharmaceuticals, Inc., Lilly. J.Todd: None. S.A.Arslanian: Advisory Panel; Novo Nordisk, Eli Lilly and Company, Consultant; Société des Produits Nestlé SA,, Other Relationship; Eli Lilly and Company, AstraZeneca, Research Support; Novo Nordisk, Eli Lilly and Company. N.T.Chang: None. L.M.Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape. L.L.Levitsky: None. J.E.Sprague: Research Support; Eli Lilly and Company, Rhythm Pharmaceuticals, Inc. Funding National Institutes of Health (K23DK120932)

P902 Native American Mapuche ancestry is related to higher IBD risk in Chileans

Abstract Background Most genetic association studies rely on Caucasian, African and Asian individuals with inconsistent results depending on the population investigated, suggesting that genetic susceptibility to inflammatory bowel disease (IBD) may depend on interactions between ethnicity and genetic-environmental factors. Aim: To explore the contribution of genetic ancestry to IBD risk in Chileans. Aim: To explore the contribution of genetic ancestry to IBD risk in Chileans. Methods 192 Chilean IBD patients were genotyped using Illumina’s Global Screening Array. Genotype data was combined with similar information from 3147 population-based Chilean controls from a published study on gallstones, body mass index, c-reactive protein and gallbladder cancer in Chileans (Barahona et al., Hepatology 2021). The individual proportions of Aymara, African, European and Mapuche ancestry were estimated using the software ADMIXTURE (supervised estimation). Using the statistical software R version 4.2.1, we calculated the odds ratios (OR) and 95% confidence intervals (CI) for gender, as well as age and ancestry proportions grouped into quartiles using the library “epitools”. Results Table 1 shows the investigated characteristics of the study population and their association with IBD risk. For example, the 1st and 3rd quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7% and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52-3.48) for the lowest versus the highest group. Conclusion The type and proportion of Native American ancestry in Chileans seems to be associated with IBD risk.

Collection of genetic data in ethnic‐based studies across Aymaras, Quechuas and Mestizos: the challenges of the Genetics of Alzheimer’s in Peruvian Population (GAPP) study

AbstractBackgroundThe Genetics of Alzheimer’s Disease in Peruvian Population (GAPP) study aims to investigate genetic and environmental risk factors for Alzheimer’s Disease (AD) in Peru. The project is led by Columbia University (CU, New York, US) and the Instituto Peruano de Neurociencias (IPN, Lima, Peru). For the past year and a half, despite the ongoing COVID‐19 pandemic, the study has collected data on cognitive function, health, diet and numerous clinical and biological risk factors for AD. In addition, we collected blood samples for DNA extraction as well as serum and plasma to look at core AD biomarkers.MethodRecruitment prioritized populations from south Peru, the Quechuas and Aymaras, because of their high proportion of Native American ancestry (or, in other words, low admixture with European ancestry) as well as Mestizo (mixed Native‐European ancestry). Three recruitment sites were established in Lima, Puno and Arequipa. Interviewers were trained to clinically and cognitively assessed the participants and collect and ship blood samples to the main site (IPN). DNA samples were then sent to CU for processing. Serum and plasma samples were processed in Lima and stored at ‐80C for batch shipping to CU. DNA samples were sent to CD Genomics and Children’s Hospital of Philadelphia for APOE genotyping and GWAS, respectively.ResultA database with 350 participants has been created. Blood samples from all participants were collected; 268 successfully underwent GWAS and APOE genotyping. An additional 82 samples are pending QC and genotyping. No samples were dropped at extraction, and only 0.7% failed DNA quality standards for genotyping.ConclusionSample collections for genetic studies in South American indigenous populations such as Peru represent important logistic challenges. The use of blood as a main source of DNA provides an effective and reliable source for genetic data analysis. Plasma and serum biomarkers will provide additional insights into the disease manifestations and validation of the clinical diagnosis in these underrepresented populations. Ongoing recruitment will augment the analytical power of the cohort by collecting blood, serum and plasma samples from additional GAPP participants.

Social injustice unveiled by genetic analysis: Argentina as a case study.

The population of the American countries is genetically heterogeneous, whose genesis result from of recent admixture events. In this process, the transoceanic European component displaced the original inhabitants of the continent. To investigate whether socially differentiated cohorts exhibit underlying ancestry components within an urban admixed population, two cohorts of individuals inhabiting Argentina were studied. One cohort included genetically unrelated individuals involved in voluntary paternity testing while the other included sexual or blood-crime suspects. We analyzed over 2500 unrelated individuals: four Native American maternal lineage mtDNA markers in 1024 samples, five Y chromosome haplogroups in 658 male samples, 24 autosomal ancestry informative markers (AIMs) in 205 samples, and 15 autosomal short tandem repeats (STRs) in 1557 samples; countrywide and divided by regions. While our results confirm a tricontinental ethnic contribution to both cohorts, their proportions showed statistically significant differences, with a higher proportion of Native American ancestry in the cohort linked to violent crimes compared to those in paternity testing. This hallmark was observed with all the marker sets used and at various levels of analysis. Since paternity tests are costly, socio-economic differences might help to interpret our observations. The effect of discrimination against descendants of Native American minorities, and exposure to violent social environments, might link marginal groups to criminality. Our findings underscore the relevance of proper social management since only by improving living conditions, reducing discrimination, promoting education, and providing job opportunities will it be possible to attain equality in a heterogeneous society. Genetic markers proved to be highly informative in unveiling unexpected social differences.

Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population

Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10–6). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10–10). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America.

Genetic Ancestry and Skeletal Toxicities Among Childhood Acute Lymphoblastic Leukemia Patients in the DFCI 05-001 Cohort

Background: Despite outstanding cure rates of pediatric acute lymphoblastic leukemia (ALL), Blacks and Hispanics have inferior survival than Whites. We recently reported that among 794 children from DFCI ALL Consortium Protocol 05-001 trial, Hispanic patients had significantly lower rates of fracture and osteonecrosis, but higher risk of relapse and death compared with non-Hispanic Whites (PMID: 29090520). Studies from other groups have reported inferior ALL outcomes in children with Native American ancestry, however the association between genetic ancestry and skeletal toxicities has not been explored. We examined whether genetic inheritance could provide an explanation for the reduced incidence of skeletal toxicities in Hispanic patients in DFCI 05-001. Methods: A total of 576 DNA samples extracted from bone marrow samples or blood samples obtained during remission, including 2% blind duplicates, were genotyped using the Illumina OmniExpress Beadchip array. After data QC and cleaning, 449 ALL patients were retained in the final analysis. Estimates of global genetic ancestry were derived from STRUCTURE program, which was used to re-classify individuals with discordant clinical race/ethnicity as reported by study site, and to assign individuals with unknown race/ethnicity information to an ethnic group when possible. Regression model for the subdistribution hazard of the cumulative incidence function was used to relate clinical race/ethnicity, genetically reclassified race/ethnicity, and genetic ancestry respectively with risk of fracture and osteonecrosis, with death and recurrence as competing risk factors while controlling for age, gender and baseline clinical factors. Cox proportional regression models were used to test race/ethnicity and ancestry with overall survival (OS) and event-free survival (EFS). Results: Among the 449 patients analyzed, average age was 6.7 years; 26% of patients were ≥10 years and 44% were female. The demographic and clinical characteristics of patients with genotype data were similar to those of the overall cohort, although the proportion of Hispanics was slightly lower in the genotyped sub-cohort (17% vs. 21%), whereas the rates of fracture and osteonecrosis were higher (fracture: 25% vs. 18%; osteonecrosis: 10% vs. 8%). Based on clinical race/ethnicity, 66% of patients were non-Hispanic White, 17% were Hispanic, 5% were non-Hispanic Black, 3% were Asian, and 10% were reported as Other. Genetic ancestry analyses revealed that non-Hispanic White patients had a median of 96% European ancestry, non-Hispanic Black patients had a median of 76% African ancestry, and Asian patients had a median of 58% Asian ancestry. The genetic make-up of Hispanic patients in the 05-001 cohort was more admixed, with 23% Native American and 17% African ancestry, higher than the national average (18% and 6%, respectively). After genetic reassignment, racial/ethnic groups were as follows: 68% non-Hispanic White, 17% Hispanic, 9% non-Hispanic Black, 6% Asian, and 1% unassigned. In analysis of genetically reassigned race/ethnicity with skeletal toxicities, Hispanic and Black patients had significantly lower risk of fracture compared with white patients (Hispanic: subdistribution hazard ratio [SHR]=0.42, 95% confidence interval [CI]=0.22, 0.81; Black: HR=0.28, 95%CI=0.10, 0.75). These groups also had significantly less osteonecrosis (Hispanic: SHR=0.24, 95%CI=0.08, 0.78; Black: SHR=0.12, 95%CI=0.02, 0.93). Similar results were observed when using clinical race/ethnicity. Further analyses revealed that African genetic ancestry, but not Native American ancestry was associated with lower risk of fracture and osteonecrosis in a dose-dependent manner (Table 1). In analysis of death and recurrence, those with higher proportion of Native American ancestry had significantly higher risk of death/recurrence after adjustment (OS: hazard ratio [HR]=4.00, 95%CI=1.45, 11.02; EFS: HR=2.07, 95%CI=1.13, 3.79). Analysis of single variants and polygenic risk scores with skeletal toxicities and survival outcomes is ongoing. Conclusion: Hispanic children and adolescents from the DFCI 05-001 cohort, had highly heterogenous genetic ancestral make-up. Among Hispanic patients, the observed lower risk of skeletal toxicities might be driven by African ancestry, whereas poorer survival observed might be driven by Native American ancestry. Disclosures Silverman: Servier: Consultancy, Research Funding; Takeda: Consultancy.

Whole-exome sequencing in maya indigenous families: variant in PPP1R3A is associated with type 2 diabetes.

It has been presumed that increased susceptibility in Mexicans to type 2 diabetes (T2D) is attributed to the Native American genetic ancestry. Nonetheless, it is not known if there are private genetic variants that confer susceptibility to develop T2D in our population. The Maya indigenous group has the highest proportion of Native American ancestry (98%) which makes it a representative group of the original peoples of Mexico. Thus, the aim of the present study is to identify new genetic variants associated with T2D in Maya families. Whole-exome sequencing was performed on DNA samples from Maya families with a third-generation family history of T2D only in one parental line. Four variants were identified for APOB, PPP1R3A, TPPP2, and GPR1 genes, and were further tested for association with T2D in 600 unrelated Maya in a case-control study. For the first time, rs1799999 in PPP1R3A was associated with risk of T2D in Mayan Mexican individuals (OR = 1.625, P = 0.014). Interestingly, carriers of rs1799999 presented increased values of HOMA-IR. In addition, rs1801702 in APOB was associated with total cholesterol and LDL-C (P = 0.019 and P = 0.020, respectively) in normoglycemic individuals; rs3732083 in GPR1 with HOMA-IR (P = 0.016) and rs9624 in TPPP2 with total cholesterol and triglycerides (P = 0.002 and P = 0.005, respectively) in T2D subjects. Overall, these findings support the idea that there are other genetic variants yet to be described, involved in T2D development in Maya population, being insulin resistance and lipid metabolism the main mechanisms implicated. Thus, these results can contribute to the understanding of diabetes genetic background in Mexican population.

Population structure in Argentina.

We analyzed 391 samples from 12 Argentinian populations from the Center-West, East and North-West regions with the Illumina Human Exome Beadchip v1.0 (HumanExome-12v1-A). We did Principal Components analysis to infer patterns of populational divergence and migrations. We identified proportions and patterns of European, African and Native American ancestry and found a correlation between distance to Buenos Aires and proportion of Native American ancestry, where the highest proportion corresponds to the Northernmost populations, which is also the furthest from the Argentinian capital. Most of the European sources are from a South European origin, matching historical records, and we see two different Native American components, one that spreads all over Argentina and another specifically Andean. The highest percentages of African ancestry were in the Center West of Argentina, where the old trade routes took the slaves from Buenos Aires to Chile and Peru. Subcontinentaly, sources of this African component are represented by both West Africa and groups influenced by the Bantu expansion, the second slightly higher than the first, unlike North America and the Caribbean, where the main source is West Africa. This is reasonable, considering that a large proportion of the ships arriving at the Southern Hemisphere came from Mozambique, Loango and Angola.

Forensic parameters and admixture in Mestizos from five geographic regions of Mexico based on 20 autosomal STRs (Powerplex 21 system).

We analyzed Mestizo (admixed) population samples from different geographic regions of Mexico (n= 1283) with 20 autosomal STRs (PowerPlex® 21, Promega Corp.). Allele frequencies and forensic parameters from the Northwest, Northeast, West, Center, and Southeast regions are reported, as well as from the pooled Mexican population sample. The combined PD and PE for this 20 STR system were > 0.9999999999 and > 0.99999996593% in all five population samples, respectively. Analysis of molecular variance (AMOVA) of these Mexican population samples, plus Monterrey (Northeast) and Mexico (Center) Cities, showed low but significant differences among Mexican-Mestizos from the seven populations (Fst = 0.20%; p = 0.0000). Structure analysis showed the highest proportion of Native American ancestry in Mexico City, Center, and Southeast regions, respectively, which was in agreement with the estimated genetic distances represented in a MDS plot and a NJ tree. The best fit of population clusters (K = 4) obtained with the Structure software indicates that Mexican-Mestizos are mainly composed by European, African, and two Native American ancestries. The European and Native American ancestries displayed a contrary gradient, increasing toward the North-West and South-Southeast, respectively. These 20 autosomal STR loci improved the admixture estimation regarding previous studies with the 13 CODIS-STRs, as supported by the higher similarity with previous estimates based on genome-wide SNP. In brief, this study validates the confident use of the PowerPlex® 21 system for human identification purposes in Mestizo populations throughout the Mexican territory.

Susceptibility background for type 2 diabetes in eleven Mexican Indigenous populations: HNF4A gene analysis.

The genetic risk of developing type 2 diabetes (T2D) increases in parallel with the proportion of Native American ancestry. Mestizo Mexicans have a 70% Native Amerindian genetic background. The T130I polymorphism in the HNF4A gene has been associated with early-onset T2D in mestizo Mexicans. Thus, the aim of the present study was to evaluate the frequency and relationship of the T130I variant in the HNF4A gene with risk factors for developing T2D in eleven indigenous groups from Mexico. In two groups, all exons of the HNF4A gene were directly sequenced; in the remaining the T130I polymorphism was analyzed by restriction fragment length polymorphism. Ancestry informative markers were assessed to confirm the Amerindian component. An additional analysis of EHH was carried out. Interestingly, HNF4A gene screening revealed only the presence of the T130I polymorphism. The range frequency of the risk allele (T) in the indigenous groups was from 2.7 to 16%. Genotypic frequencies (T130I/I130I) were higher and significantly different from those of all of the populations included in the HapMap Project (P<0.005). EHH scores suggest a positive selection for T130I polymorphism. Metabolic traits indicate a relationship between the T130I/I130I genotypes with high triglyceride concentrations in the indigenous groups (P<0.005). These results strongly suggest that the high frequency of the T130I polymorphism and its biological relationship with dysfunction in lipid metabolism in Mexican indigenous groups is a risk factor for the developing of T2D in Mexicans.

Genetic Ancestry and Susceptibility to Late-Onset Alzheimer Disease (LOAD) in the Admixed Colombian Population.

Differences in the prevalence of dementia among populations and in the effect of apolipoprotein E (APOE) on the emergence of Alzheimer disease (AD), which is the main type of dementia, have been reported. This study estimated the ancestry of a group of individuals with late-onset Alzheimer disease (LOAD) (N=280) and established whether there were any differences when compared with a control group (N=357) in a sample of the Colombian population. When the analyses were adjusted for known risk factors such as age, sex, presence of APOE[Latin Small Letter Open E]4, socioeconomic status, educational attainment, and place of birth, African ancestry was associated with an increased LOAD risk (odds ratio: 1.55; 95% confidence interval, 1.09-2.03; P=0.029), whereas Native American ancestry was associated with lower risk (odds ratio: 0.75; 95% confidence interval, 0.61-0.98; P=0.046), for every 10% increase in ancestry. In addition, there were significant differences in the proportion of Native American ancestry between carriers and noncarriers of the APOE[Latin Small Letter Open E]4 allele (Mann-Whitney U test, P=0.047), with noncarriers having higher mean Native American ancestry when compared with carriers. Our results are consistent with the presence of variants of African origin in the genome of the Colombian population and different from APOE[Latin Small Letter Open E]4 that represents a risk factor for the development of LOAD, whereas variants of Native American origin may be conferring protection. However, unknown environmental factors or epigenetic differences among continental groups could also explain the observed associations.

Unexpected inverse correlation between Native American ancestry and Asian American variants of HPV16 in admixed Colombian cervical cancer cases

BackgroundEuropean (E) variants of HPV 16 are evenly distributed among world regions, meanwhile Non-European variants such as European-Asian (EAs), Asian American (AA) and African (Af) are mostly confined to Eastern Asia, The Americas and African regions respectively. Several studies have shown that genetic variation of HPV 16 is associated with the risk of cervical cancer, which also seems to be dependent on the population. This relationship between ethnicity and variants have led to the suggestion that there is co-evolution of variants with humankind. Our aim was to evaluate the relationship between the individual ancestry proportion and infection with HPV 16 variants in cervical cancer. MethodsWe examined the association between ancestry and HPV 16 variants in samples of 82 cervical cancer cases from different regions of Colombia. Individual ancestry proportions (European, African and Native American) were estimated by genotyping 106 ancestry informative markers. Variants were identified by PCR amplification of the E6 gene, followed by reverse line blot hybridization (RLB) with variants specific probes. ResultsOverall European (E) and Asian American (AA) variants frequency was 66.5% and 33.5% respectively. Similar distribution was observed in cases with higher proportions of European or African ancestry. A higher Native American ancestry was significantly associated with higher frequency of E variants (median ancestry>23.6%, Age and place of birth adjusted OR: 3.55, 95% CI: 1.26–10.03, p=0.01). Even further, an inverse geographic correlation between Native American ancestry and frequency of infections with AA variants was observed (ρ=−0.825, p=0.008). Regions with higher proportion of Native American ancestry had a lower frequency of AA variants of HPV 16. ConclusionsThis study suggests replacement of AA variants by E variants of human papillomavirus 16 in cervical cancer cases with high Native American ancestry.

Cuba: exploring the history of admixture and the genetic basis of pigmentation using autosomal and uniparental markers.

We carried out an admixture analysis of a sample comprising 1,019 individuals from all the provinces of Cuba. We used a panel of 128 autosomal Ancestry Informative Markers (AIMs) to estimate the admixture proportions. We also characterized a number of haplogroup diagnostic markers in the mtDNA and Y-chromosome in order to evaluate admixture using uniparental markers. Finally, we analyzed the association of 16 single nucleotide polymorphisms (SNPs) with quantitative estimates of skin pigmentation. In the total sample, the average European, African and Native American contributions as estimated from autosomal AIMs were 72%, 20% and 8%, respectively. The Eastern provinces of Cuba showed relatively higher African and Native American contributions than the Western provinces. In particular, the highest proportion of African ancestry was observed in the provinces of Guantánamo (40%) and Santiago de Cuba (39%), and the highest proportion of Native American ancestry in Granma (15%), Holguín (12%) and Las Tunas (12%). We found evidence of substantial population stratification in the current Cuban population, emphasizing the need to control for the effects of population stratification in association studies including individuals from Cuba. The results of the analyses of uniparental markers were concordant with those observed in the autosomes. These geographic patterns in admixture proportions are fully consistent with historical and archaeological information. Additionally, we identified a sex-biased pattern in the process of gene flow, with a substantially higher European contribution from the paternal side, and higher Native American and African contributions from the maternal side. This sex-biased contribution was particularly evident for Native American ancestry. Finally, we observed that SNPs located in the genes SLC24A5 and SLC45A2 are strongly associated with melanin levels in the sample.

Correlation analysis of genetic admixture and social identification with body mass index in a Native American community.

Body mass index (BMI) is a well-known measure of obesity with a multitude of genetic and non-genetic determinants. Identifying the underlying factors associated with BMI is difficult because of its multifactorial etiology that varies as a function of geoethnic background and socioeconomic setting. Thus, we pursued a study exploring the influence of the degree of Native American admixture on BMI (as well as weight and height individually) in a community sample of Native Americans (n = 846) while accommodating a variety of socioeconomic and cultural factors. Participants' degree of Native American (NA) ancestry was estimated using a genome-wide panel of markers. The participants also completed an extensive survey of cultural and social identity measures: the Indian Culture Scale (ICS) and the Orthogonal Cultural Identification Scale (OCIS). Multiple linear regression was used to examine the relation between these measures and BMI. Our results suggest that BMI is correlated positively with the proportion of NA ancestry. Age was also significantly associated with BMI, while gender and socioeconomic measures (education and income) were not. For the two cultural identity measures, the ICS showed a positive correlation with BMI, while OCIS was not associated with BMI. Taken together, these results suggest that genetic and cultural environmental factors, rather than socioeconomic factors, account for a substantial proportion of variation in BMI in this population. Further, significant correlations between degree of NA ancestry and BMI suggest that admixture mapping may be appropriate to identify loci associated with BMI in this population.

Evaluating the X Chromosome-Specific Diversity of Colombian Populations Using Insertion/Deletion Polymorphisms

The European and African contribution to the pre-existing Native American background has influenced the complex genetic pool of Colombia. Because colonisation was not homogeneous in this country, current populations are, therefore, expected to have different proportions of Native American, European and African ancestral contributions. The aim of this work was to examine 11 urban admixed populations and a Native American group, called Pastos, for 32 X chromosome indel markers to expand the current knowledge concerning the genetic background of Colombia. The results revealed a highly diverse genetic background comprising all admixed populations, harbouring important X chromosome contributions from all continental source populations. In addition, Colombia is genetically sub-structured, with different proportions of European and African influxes depending on the regions. The samples from the North Pacific and Caribbean coasts have a high African ancestry, showing the highest levels of diversity. The sample from the South Andean region showed the lowest diversity and significantly higher proportion of Native American ancestry than the other samples from the North Pacific and Caribbean coasts, Central-West and Central-East Andean regions, and the Orinoquian region. The results of admixture analysis using X-chromosomal markers suggest that the high proportion of African ancestry in the North Pacific coast was primarily male driven. These men have joined to females with higher Native American and European ancestry (likely resulting from a classic colonial asymmetric mating type: European male x Amerindian female). This high proportion of male-mediated African contributions is atypical of colonial settings, suggesting that the admixture occurred during a period when African people were no longer enslaved. In the remaining regions, the African contribution was primarily female-mediated, whereas the European counterpart was primarily male driven and the Native American ancestry contribution was not gender biased.

Revisiting the Genetic Ancestry of Brazilians Using Autosomal AIM-Indels

There are many different studies that contribute to the global picture of the ethnic heterogeneity in Brazilian populations. These studies use different types of genetic markers and are focused on the comparison of populations at different levels. In some of them, each geographical region is treated as a single homogeneous population, whereas other studies create different subdivisions: political (e.g., pooling populations by State), demographic (e.g., urban and rural), or ethnic (e.g., culture, self-declaration, or skin colour). In this study, we performed an enhanced reassessment of the genetic ancestry of ~ 1,300 Brazilians characterised for 46 autosomal Ancestry Informative Markers (AIMs). In addition, 798 individuals from twelve Brazilian populations representing the five geographical macro-regions of Brazil were newly genotyped, including a Native American community and a rural Amazonian community. Following an increasing North to South gradient, European ancestry was the most prevalent in all urban populations (with values up to 74%). The populations in the North consisted of a significant proportion of Native American ancestry that was about two times higher than the African contribution. Conversely, in the Northeast, Center-West and Southeast, African ancestry was the second most prevalent. At an intrapopulation level, all urban populations were highly admixed, and most of the variation in ancestry proportions was observed between individuals within each population rather than among population. Nevertheless, individuals with a high proportion of Native American ancestry are only found in the samples from Terena and Santa Isabel. Our results allowed us to further refine the genetic landscape of Brazilians while establishing the basis for the effective application of an autosomal AIM panel in forensic casework and clinical association studies within the highly admixed Brazilian populations.

New Mexican Hispanic smokers have lower odds of chronic obstructive pulmonary disease and less decline in lung function than non-Hispanic whites.

The epidemiology of cigarette smoking-related chronic obstructive pulmonary disease (COPD) is not well characterized in Hispanics in the United States. Understanding how ethnicity influences COPD is important for a number of reasons, from informing public health policies to dissecting the genetic and environmental effects that contribute to disease. The present study assessed differences in risk between Hispanics and non-Hispanic whites for longitudinal and cross-sectional COPD phenotypes. Genetic ancestry was used to verify findings based on self-reported ethnicity. Hispanics in New Mexico are primarily differentiated from non-Hispanic whites by their proportion of Native American ancestry. The study was performed in a New Mexican cohort of current and former smokers. Self-reported Hispanic and non-Hispanic white ethnicity was validated by defining genetic ancestry proportions at the individual level using 48 single-nucleotide polymorphism markers. Self-reported ethnicity and genetic ancestry were independently used to assess associations with cross-sectional and longitudinal measures of lung function. Multivariable models were adjusted for indicators of smoking behavior. Self-reported Hispanic ethnicity was significantly associated with lower odds of COPD (odds ratio, 0.49; 95% confidence interval, 0.35-0.71; P = 0.007), and this protection was validated by the observation that Hispanic smokers have reduced risk of rapid decline in lung function (odds ratio, 0.48; 95% confidence interval, 0.30-0.78; P = 0.003). Similar findings were noted when Native American genetic ancestry proportions were used as predictors instead of self-report of Hispanic ethnicity. Hispanic ethnicity is inversely associated with cross-sectional and longitudinal spirometric COPD phenotypes even after adjustment for smoking. Native American genetic ancestry may account for this "Hispanic protection."