Indigenous Ancestry Research Articles

Racializing Mestizos and Mestizas in the Philippines—Dean Worcester’s Anthropometric Types in the Early 20th Century

In the Spanish Empire, the term mestizo/mestiza denoted, overwhelmingly, people of so-called “mixed” European and indigenous ancestry, but there existed also some regional adaptations with differing genealogies such as the mestizos de sangley in the Philippines. The article traces some developments of the application and racialization of the term mestizo shortly after the end of the Spanish Empire in the Philippines under U.S. rule. It will look at photographs that were taken in by Dean Worcester, secretary of the interior, and his staff, in order to apply and develop theories of the biologist racism, which in the early twentieth century was en vogue all over the globe. Worcester and his crew took the photographs during their expeditions and used them to illustrate their hypotheses about racialized taxonomies, adapting and further developing Spanish colonial ideas. I will contrast them with a photograph from a local studio in Mindanao. The photographs stem from the photographic collection of the Rautenstrauch-Joest Museum in Cologne, Germany.

Mortality risk among older adults of indigenous ancestry with asymptomatic intracranial atherosclerotic stenosis. A population-based, longitudinal prospective study in rural Ecuador.

Mortality risk among older adults of indigenous ancestry with asymptomatic intracranial atherosclerotic stenosis. A population-based, longitudinal prospective study in rural Ecuador.

Abstract 4083: Ancestral background and germline mutations in head and neck cancer: An analysis of disparities in genetic risk factors using the All of Us database

Background: Head and Neck Cancer (HNC) ranks as the seventh most common cancer globally, yet significant disparities persist in mortality rates across ethnic groups, especially in the United States (US). Hispanic and Non-Hispanic (NH) Black men exhibit higher cancer-specific mortality rates for HNC compared to NH White men, indicating gaps in cancer prevention, early detection, and genetic risk profiling for these groups. The influence of genetic ancestry on HNC risk remains understudied, particularly within Hispanics, who have a diverse ancestral composition. This study aims to elucidate the association between genetic ancestry and HNC, while also analyzing mutations in four genes associated with HNC: FAT1, POLB, TP53, and CDKN2A. Methods: Demographic information, electronic health records, and microarray data for this study was sourced from the All of Us Research Program. A cohort of 2,552 individuals was identified, where half were of HNC cases, and half were demographically matched controls without a cancer diagnosis. Mann-Whitney U test was performed to analyze the differences between ancestry percentages within cancer and non cancer groups. Associations of genetic variants with cancer status or ancestral genetic makeup were assessed with Chi-square tests. Results: Self-reported Hispanic or Latino participants in our cohort had an approximate average of 83% Indigenous American ancestry, 8% European ancestry, 6% African ancestry, 1% Eastern Asian ancestry, 0.6% Southern Asian ancestry, and 0.5% Middle Eastern ancestry. We identified that individuals with a higher percentage of Indigenous American ancestry were more likely to have a negative cancer diagnosis (p<0.05). Conversely, individuals with a higher percentage of European ancestry were more likely to have a positive HNC diagnosis (p<0.01). We did not identify significant results relating African ancestry to the diagnosis of HNC. Six single nucleotide polymorphisms (SNPs) within the four genes studied had a significant association to cancer diagnosis (p<0.05). There was a significant association in two of these SNPs between genotypes and predominant ancestry. Individuals with predominant Indigenous American ancestry were more likely to have the CT genotype for rs3136719 in the POLB gene (p<0.05). For rs3218009 in the CDKN2A gene, individuals with predominant European ancestry were associated with the CG genotype (p<0.05). Conclusions: We identified that a high percentage of Indigenous American ancestry was linked to reduced HNC risk, while a high percentage of European ancestry was associated with increased risk, suggesting ancestry-related germline mutations may influence susceptibility. These findings indicate that the increased mortality rate related to HNC in Black and Latino populations in the US could be more significantly affected by social determinants of health. Citation Format: Mayra S. Haedo-Cruz, Grace E. Vélez-Crespo, Natalie Álamo-Rodríguez, Vivian Colón-López, Julie Dutil, Josué Pérez-Santiago. Ancestral background and germline mutations in head and neck cancer: An analysis of disparities in genetic risk factors using the All of Us database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4083.

Ethnic solidarity in non-programmatic linkages. The case of Mapuche mayors in Chile

ABSTRACT Research on ethnic politics has extensively examined electoral representation and ethnic parties. Nevertheless, nonprogrammatic linkages between indigenous representatives and citizens remain underexplored, particularly in formal institutional settings. To address this gap, we analyse 49,845 formal meetings (hearings) between mayors and citizens in Chile to assess how ethnic ancestry influences political mediation at the local level. Our findings reveal two key patterns. First, mayors of indigenous ancestry demonstrate a higher propensity to grant meetings for individual or targeted requests, suggesting increased receptivity to the fundamental needs of citizens. Second, we find evidence of ethnic solidarity, as indigenous mayors exhibit a greater propensity to grant meetings for requests of co-ethnic citizens, particularly for individual concerns. These findings highlight the influence of ethnic identity on political interactions, even in highly institutionalised settings. Our study extends research on ethnic representation beyond electoral dynamics, demonstrating that ethnic identities shape everyday governance and local political mediation.

Novel Intermediate ATXN10 Alleles in the Healthy Peruvian Population: A Matter of Indigenous American Ethnic Origin.

Spinocerebellar ataxia type 10 (SCA10) is a neurodegenerative disease predominant in Latin American individuals with Indigenous American ancestry. SCA10 is caused by an expansion of ATTCT repeat within the ATXN10 gene. Healthy individuals carry 9-32 ATTCT repeats, whereas SCA10 patients carry an expansion of 280 repeats and higher. Recently, intermediate alleles (over than 32 repeats) have been identified in healthy Peruvian Indigenous American individuals, with unclear significance. This study aims to characterize the variability of the ATTCT repeats within the ATXN10 gene across self-declared Indigenous American and Mestizo subpopulations from Peru. A total of 871 samples (754 Mestizo and 117 Indigenous American) were analyzed using PCR, and RP-PCR when suspecting apparent homozygosity due to larger alleles. 8.7% of the total of healthy individuals (76/871) carry at least one intermediate allele. The 14-repeat allele being the most common for both subpopulations (41.5%). Intermediate alleles were detected in the Peruvian population (4.5%) with a significantly higher frequency among self-declared Indigenous American compared to Mestizo, suggesting a possible association with the ethnic origin. The G allele at the SNP rs41524547 had a frequency of 51.39% in individuals with intermediate alleles, with not significantly difference between subpopulations. Further analysis should be performed to confirm the size and composition of ATTCT repeat tract, as well as the contribution of rs41524547 in SCA10.

PRÁTICAS PEDAGÓGICAS, MEMÓRIA E ANCESTRALIDADE ÉTNICO-RACIAL NO TERRITÓRIO: EDUCAÇÃO E DIREITOS HUMANOS NO SÍTIO LEITE, JUAZEIRO DO NORTE, CEARÁ

This paper aims to discuss how certain pedagogical practices in non-formal contexts can promote the preservation of the memory and ancestry of the black/indigenous community of the Sítio Leite territory, in Serra do Catolé, Juazeiro do Norte-CE. This is a qualitative study that involved field research with semi-structured interviews with the community's residents and intervention actions with the screening of short films and, later, discussion groups. The results obtained through the meetings with the community pointed to a greater awareness of their rights as black and indigenous people. In addition, the discussions allowed for greater knowledge of their history, as well as the appreciation of black and indigenous memory and ancestry evidenced by the sharing of stories and perceptions about the collective cultural identity of the community. It is concluded that the pedagogical practices used in non-formal spaces can contribute more effectively to human rights education with an emphasis on ethnic-racial relations, with positive implications for strengthening ethnic identity in the territory. Educating about human rights is an essential task for valuing the memory and ancestry of several black and indigenous communities that have long been marginalized. The Sítio Leite community has faced this type of social marginalization and lack of access to essential rights. In this context, pedagogical practices have contributed to the political strengthening of the community and to their understanding as subjects of knowledge and rights.

The impact of Indigenous American-like ancestry on risk of acute lymphoblastic leukemia in Hispanic/Latino children.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with Hispanic/Latino children having a higher incidence of ALL than other racial/ethnic groups. Genetic variants, particularly ones found enriched in Indigenous American (IA)-like ancestry and inherited by Hispanics/Latinos, may contribute to this disparity. In this study, we characterized the impact of IA-like ancestry on overall ALL risk and the frequency and effect size of known risk alleles in a large cohort of self-reported Hispanic/Latino individuals. We also performed genome-wide admixture mapping analysis to identify potentially novel ALL risk loci. We found that global IA ancestry was positively associated with ALL risk, but the association was not significant after adjusting for socio-economic indicators. In a series of local ancestry analyses, we uncovered that at known ALL risk loci, increasing copies of the IA-like haplotype were positively and significantly associated with ALL case-control status. Further, the IA-like haplotype had ~1.33 times the odds of harboring the risk allele compared to non-IA-like haplotypes. We found no evidence of interaction between genotype and ancestry (local or global) in relation to ALL risk. Admixture mapping identified association signals on chromosomes 2 (2q21.2), 7 (7p12.2), 10 (10q21.2), and 15 (15q22.31); however, only the variants at 7p12.2 and 10q21.2 replicated in additional cohorts. Taken together, our results suggest that increased risk of ALL in Hispanic/Latino children may be conferred by higher frequency of risk alleles within IA-like ancestry, which can be leveraged as targets of new precision health strategies and therapeutics.

Afro-diasporic Expressions in Contexts of Invisibility: A Study of a Cemetery and Afro-Argentine Dwellings of the Twentieth Century

ABSTRACT Since the nineteenth century, the construction of a white identity linked to Europe in Argentina has invisibilized Indigenous and African ancestry, denying and silencing non-European memories and ethnicities. In the province of Entre Ríos in the Rio de la Plata littoral, a border region since the colonial times, the discourse aimed at Europeanisation promoted the idea of a whitening process. This idea ignored the importance of the cultural constructs of Afro-descendant, Indigenous, and mestizo populations. The interdisciplinary research carried out in this territory contributes to the knowledge of the regional Afro-descendant past and present. I present the results of surveys and excavations around a cemetery and rural Afro-descendant dwellings. When put in dialogue with current memories and oralities, these results contribute to reinterpret and make visible the ontologies of African roots present in the mid-twentieth century. This revitalizes and provides tools for current processes of identity re-emergence.

LONGEVITY IN CULTURAL CONTEXT: FINDINGS FROM FOUR CENTENARIAN STUDIES

Abstract Life expectancy varies across cultural and international groups, but each culture contains long-lived individuals. To what extent survivors in different cultural groups have common or divergent characteristics is still being determined. The purpose of the symposium is to compare and contrast physical, functional, and mental health characteristics among four different cultural groups of centenarians: African American centenarians from the Health and Retirement Study, Hawaii centenarians of Japanese ancestry from the Kuakini Hawaii Centenarian Study, Japanese centenarians, and Native Americans from the Oklahoma Centenarian Study. The first study showcases longevity predictors for African Americans in the Health and Retirement Study, highlighting family longevity, individual and family resources, health behaviors, and physical, functional, and mental health. The second study utilizes centenarian data from the Kuakini Hawaii Centenarian Study, featuring their unique survivorship characteristics as participants age from 70 to 100 years. The third presentation highlights Japanese centenarians and reveals the diversity of physical and mental well-being of centenarians in Japan. Findings highlight the high bed-bound ratio among centenarians in Japan. Finally, the Oklahoma Centenarian Study identifies themes pertaining to underlying cultural influences using oral narratives of centenarian descendants of indigenous ancestry. The themes of “transmission of historical trauma,” “shared collectivism,” “leisure and sporting,” and “educational attainment“signify themes of adaptation and survival. The four centenarian studies suggest similarities and essential differences when comparing these exceptional cultural groups of survivors. Practitioners and policymakers should be responsive to the diverse needs of centenarians who provide cultural individuality to their communities.

Inbreeding and Gallbladder Cancer Risk: Homozygosity Associations Adjusted for Indigenous American Ancestry, BMI, and Genetic Risk of Gallstone Disease.

Latin Americans have a rich genetic make-up that translates into heterogeneous fractions of the autosomal genome in runs of homozygosity (FROH) and heterogeneous types and proportions of indigenous American ancestry. While autozygosity has been linked to several human diseases, very little is known about the relationship between inbreeding, genetic ancestry, and cancer risk in Latin Americans. Chile has one of the highest incidences of gallbladder cancer (GBC) in the world, and we investigated the association between inbreeding, GBC, gallstone disease (GSD), and body mass index (BMI) in 4029 genetically admixed Chileans. We calculated individual FROH above 1.5 Mb and weighted polygenic risk scores for GSD, and applied multiple logistic regression to assess the association between homozygosity and GBC risk. We found that homozygosity was due to a heterogeneous mixture of genetic drift and consanguinity in the study population. Although we found no association between homozygosity and overall GBC risk, we detected interactions of FROH with sex, age, and genetic risk of GSD that affected GBC risk. Specifically, the increase in GBC risk per 1% FROH was 19% in men (p-value = 0.002), 30% in those under 60 years of age (p-value = 0.001), and 12% in those with a genetic risk of GSD above the median (p-value = 0.01). The present study highlighted the complex interplay between inbreeding, genetic ancestry, and genetic risk of GSD in the development of GBC. The applied methodology and our findings underscored the importance of considering the population-specific genetic architecture, along with sex- and age-specific effects, when investigating the genetic basis of complex traits in Latin Americans.

PD90 Use Of Medicinal Herbs In Natura By Pregnant Women In The Amazon Region

IntroductionThere are few studies on the use medicinal herbs by pregnant women in Brazil, even though there is a wealth of knowledge about medicinal herbs among Brazilians of Indigenous, African, and European ancestry. The aim of this study was to assess the prevalence and type of herbs used by pregnant women living in the Amazon region.MethodsThis was a cross-sectional study conducted with 811 pregnant women attending 10 public antenatal clinics in Manaus, Amazonas state, Brazil. The consumption of medicinal herbs was assessed through individual 24-hour dietary recall.ResultsA total of 811 women in their second trimester (16 to 20 weeks) of pregnancy were included and 69 (8.5%) reported that they used herbs to make teas. There was a significant difference between users and non-users of medicinal teas, with a higher proportion of overweight women in the group that used teas (46.4% versus 31.9%; p=0.005). Nearly half (47.8%) of those who used medicinal teas consumed herbs with sedative effects, 23 percent consumed herbs for the relief of urinary tract symptoms, and 13 percent used herbs with digestive properties. Most women reported using natural herbs from their own gardens.Conclusions Approximately 10 percent of Brazilian women in the Amazon region consumed medicinal herbs to alleviate common symptoms of pregnancy. The most frequently used plants had sedative, urinary tract, or gastrointestinal effects. Most plants were obtained in natura from local gardens. Many of these plants have known adverse effects and their use is contraindicated during pregnancy.

New Associations with the HIV Predisposing and Protective Alleles of the Human Leukocyte Antigen System in a Peruvian Population.

The accurate determination of an individual's unique human leukocyte antigen (HLA) allele holds important significance in evaluating the risk associated with autoimmune and infectious diseases, such as human immunodeficiency virus (HIV) infection. Several allelic variants within the HLA system have been linked to either increased protection or susceptibility in the context of infectious and autoimmune diseases. This study aimed to determine the frequency and association of HLA alleles between people living with HIV (PLHIV) as the case group and Peruvian individuals without HIV with high-risk behaviors of sexually transmitted diseases as the control group. Whole exome sequencing (WES) was used to determine high-resolution HLA allelotypes using the OptiType and arcas HLA tools. The HLA alleles present in HLA classes I (A, B, and C loci) and II (DPB1, DQA1, DQB1, and DRB1 loci) were determined in a cohort of 59 PLHIV (cases) and 44 individuals without HIV (controls). The most frequent HLA alleles were A*02:01, DPB1*04:02, and DQB1*03:419 at 36%, 30%, and 28% prevalence in general population. We found that C*07:01 (p = 0.0101; OR = 10.222, 95% IC: 1.40-74.55), DQA1*03:02 (p = 0.0051; OR = 5.297, 95% IC: 1.48-19.02), and DRB1*09:01 (p = 0.0119; OR = 4.788, 95% IC: 1.39-16.44) showed an association with susceptibility to HIV infection, while DQB1*03:419 (p = 0.0478; OR = 0.327, 95% IC: 0.11-0.96) was associated with protection from HIV infection. Our findings contribute to the knowledge of HLA allele diversity in the Peruvian population (around 70% South American indigenous ancestry) lays the groundwork for further valuable large-scale use of HLA typing and offers a novel association with HIV infection that is relevant to vaccine studies.

Polygenic prediction of coronary artery disease among 130,000 Mexican adults

Abstract Background Coronary artery disease (CAD) is a leading cause of premature mortality globally. Polygenic risk scores (PRSs) have been reported to enhance CAD prediction in populations of European ancestry but evidence from other populations is limited. We assessed the transferability and relevance of eight different external PRSs to the odds of premature CAD in a Mexican population with high levels of relatedness and ancestry admixture. Methods 128,388 genotyped participants aged 35-74 years who were recruited between 1998 and 2004 into the Mexico City Prospective Study (MCPS) were included. We selected and recreated eight previously-reported CAD PRSs. The number of single nucleotide polymorphism variants included in the PRSs varied from 44 to 6,472,620. Premature CAD was defined as either self-reported history of heart attack or angina at recruitment or death before age 75 with CAD recorded on the death certificate. Age and sex-adjusted logistic regression was used to estimate the ability of each PRS to predict CAD, both overall and separately by age, sex and estimated proportion of Indigenous American ancestry. Analyses were repeated after further adjustment for conventional risk factors (blood pressure, adiposity, smoking, diabetes and highest education achieved). Risk discrimination was assessed using C-statistic. Results Of the 128,388 participants, 68% were women, mean (SD) age was 50.2±10.9 years and the average proportion of Indigenous American ancestry was 67%. CAD was identified for 3,871 (3.0%) participants; prior CAD was reported by 1,669 (1.3%) participants while 2,360 (1.8%) participants died before age 75 years with CAD mentioned on the death certificate. All eight PRSs were positively and approximately log-linearly associated with the odds of CAD, but the strength of association varied between the PRSs, ranging from a 7% increase per 1SD higher PRS (odds ratio [OR] 1.07, 95% CI 1.04-1.11) to a 33% increase (OR 1.33, 95% CI 1.29-1.37). Collectively, age, sex and (any) PRS resulted in a C-statistic of 0.70-0.71. C-statistics were slightly lower among those with a higher proportion of indigenous American ancestry. For four of the eight PRSs (including three of the four multi-ancestry PRSs) the increase in odds of CAD per 1SD higher PRS was significantly greater for men than women (eg, for the PRS with the strongest overall association with CAD the OR per 1SD higher PRS was 1.43 [95% CI 1.36-1.49] in men and 1.25 [1.20-1.31] in women). Further inclusion of conventional vascular risk factors reduced the strengths of associations of each PRS with CAD only slightly but increased the model C statistic to 0.74 in all cases. Conclusions In this population of admixed Mexican adults, existing PRSs predicted CAD reasonably well and independently of conventional vascular risk factors. Ancestry-specific instruments that more closely represent genetic variation in Mexico may further enhance polygenic prediction of CAD risk.Table 1.Baseline characteristicsFigure 1.Main analysis results

Abstract C153: Transcriptome-wide study identifies unique pathway functional clusters associated with breast cancer subtypes in population with high indigenous american ancestry

Abstract Purpose: Breast cancer incidence and outcomes differ by US census racial/ethnic category. Since large-scale genetic studies of human disease are predominately focused on populations of European ancestry, little is known about breast cancer molecular biology in Hispanic/Latinos which can widen cancer health disparities due to suboptimal translation of discoveries into clinical practice or public health policy. We aim to identify most relevant pathways in breast cancer subtype differentiation in breast cancer patients from Peru and compared them with those obtained analyzing the Cancer Genome Atlas (TCGA) Breast Cancer (BRCA) dataset and with the published results of the Molecular Profile of Breast Cancer Study (MPBCS), a multi-country Latin American cohort. Patients and Methods: Formalin fixed paraffin embedded tumor tissues samples were whole exome sequenced for a total of 271 patients recruited by the Peruvian Breast Cancer Genomics Study (PEGEN-BC). Quality control was conducted to remove genes with low counts for PEGEN and TCGA-BRCA cohorts, and only female stage II-III breast cancer patients were kept for downstream analysis. Intrinsic tumor subtypes were classified using the estrogen receptor (ER) status-adjusted PAM50 method with genefu package in R. Differential gene expression and pathway analyses between subtypes were performed by the GSEA 4.3.2 software. [LF1] [CX2] Statistical and biological significance was determined using p-values < 0.1 and absolute value of enrichment score > 1.5. Top 20 pathways for each cohort were selected and ranked for comparison. Results: PAM50 classification of the PEGEN-BC cohort defined 20.2% of tumors as Luminal A (LumA), 27.9% as Luminal B (LumB), 27.1% as HER2E, 22.5% as Basal and 2.3% as Normal. Transcriptomic pathway analysis showed that most of the significantly changed pathways were similar to previous findings in the literature, for example, proliferation pathways being upregulated in LumB, HER2E and Basal tumors, compared to the LumA subtype, and a strong dependency on the estrogen pathways for LumA and LumB. Within cohorts, we identified novel clusters of pathways that share related functions. For example, 6 out of the 20 top significant pathways in LumB vs. HER2E comparison for the PEGEN-BC cohort were glycan/glycosylation-related, suggesting the possibility of tumor immune response differences between LumB and HER2E due to glycan related pathway differences among Peruvian patients. Conclusions: We identified novel pathway clusters associated with specific breast cancer subtypes in a population with high Indigenous American ancestry from Peru. Further analyses will be conducted next to explore if the observed patterns were specific to genetic ancestry background or observed independently of genetic ancestry. Citation Format: Chenghuiyun Xu, Valentina A. Zavala, David Rocke, Xiaosong Huang, Sandro Casavilca-Zambrano, Jeannie Navarro-Vásquez, Ruddy Liendo-Picoaga, Monica Calderón, Guillermo Valencia, Patricia Rioja, Carlos A Castañeda, Zaida Morante, Silvia P. Neciosup, Hugo A Fuentes, Julio E. Abugattas, Jose M. Cotrina, Luis A. Salinas, Marco Gálvez-Nino, Jovanny Zabaleta, Andrea S. Llera, Tatiana Vidaurre, Laura Fejerman. Transcriptome-wide study identifies unique pathway functional clusters associated with breast cancer subtypes in population with high indigenous american ancestry [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C153.

Abstract A079: The impact of Indigenous American ancestry on the risk of acute lymphoblastic leukemia and the implications for future study designs

Abstract Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with Hispanic/Latino (H/L) children having up to 1.4 times the rate of ALL compared to their non-Hispanic White counterparts. This disparity has not been fully explained by environmental factors, suggesting the role of understudied genetic variants, particularly ones found in Indigenous American (IA) ancestry inherited by Latinos. In this study, we characterized the impact of IA ancestry on the frequency and effect size of known ALL risk alleles. We found that elevated risk of ALL in Latinos may be conferred by increased frequency of risk alleles due to IA ancestry. For instance, in an analysis of Latinos from the California Cancer Linkage Project (CCRLP; 1,930 cases, 2,103 controls) and the California Childhood Leukemia Study (CCLS; N = 605 cases, 515 controls), we found that, across independent known ALL loci (N=21), more loci than expected by chance showed a significant association between IA ancestry and increasing risk (p = 0.015). Compared to randomly-sampled, frequency-matched alleles from the genome, the risk alleles at all known ALL loci also showed a significant association with IA ancestry (46.9 % for known risk alleles vs. 43.5 % for matched alleles; ). The IA haplotype had 1.39 times the odds (95% CI: 1.35 – 1.43; ) of harboring the risk allele compared to the non-IA haplotype. Conversely, in a combined Latino sample of 2,535 cases and 9,035 controls, we found no evidence of GxAncestry interaction on ALL risk across all known loci (min P = 0.0026, prior to adjusting for multiple testing), suggesting that ALL risk alleles do not have increased effects on the IA ancestry background. This lack of synergism between local ancestry and genotype in ALL has methodological implications for gene discovery in admixed populations. To explore this, we implemented Tractor, a method that models genotype effects by ancestry, and thus is best powered in the presence of effect size heterogeneity by ancestry. Across known loci, we found that Tractor had 36.1% decreased power compared to standard GWAS. Taken together, our results suggest that the disproportionate burden of ALL in Latino populations may arise from the enrichment of risk alleles within the IA ancestry component, possibly driven by immunity- related selective pressures. Finally, future genetic studies of ALL in Latino patients may benefit from methods that incorporate contributions from ancestry to increase the statistical power in identifying associations, rather than leverage effect size heterogeneity across ancestries. Citation Format: Jalen Langie, Libby Morimoto, Xiaomei Ma, Catherine Metayer, Joseph L. Wiemels, Adam J. de Smith, Charleston W.K. Chiang. The impact of Indigenous American ancestry on the risk of acute lymphoblastic leukemia and the implications for future study designs [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A079.

Barriers and Facilitators to Accessing Opioid Agonist Therapy for Street-involved Adolescents and Young Adults in Vancouver.

Opioid agonist therapy (OAT) remains the first-line therapy for people with opioid use disorder. Whereas overdose rates among adolescents and young adults (AYAs) remain high, little is known about their access to OAT. Therefore, we sought to evaluate factors that shape access to OAT among AYAs aged 14 to 26 years. Data were derived from the At-Risk Youth Study, a prospective cohort study that involves street-involved AYAs who use illicit substances in Vancouver, Canada. Generalized estimating equations were used to identify factors associated with OAT enrollment from September 2005 to October 2021. A total of 759 AYAs reported at least weekly opioid or OAT use, with a median age of 23 years and 65.7% self-identifying as male. At baseline, 147 participants (19.4%) were on OAT, and another 199 (26.2%) initiated OAT during study follow-up (median number of follow-up visits, 5 [Q1-Q3, 2.5-8]). In a multivariable analysis, being <19 years old (adjusted odds ratio [AOR], 0.40; 95% confidence interval [CI], 0.23-0.71), Indigenous ancestry (OR, 0.72; 95% CI, 0.52-1.00), homelessness (AOR, 0.65; 95% CI, 0.54-0.77), drug dealing (AOR, 0.73; 95% CI, 0.61-0.87), daily opioid use (AOR, 0.47; 95% CI, 0.40-0.55), and nonfatal overdose (AOR, 0.73; 95% CI, 0.60-0.89) were negatively associated with OAT use. This study identified a low rate of OAT access among AYAs. Adolescents and young adults were less likely to be on OAT if they were <19 years old, Indigenous, and possessed certain risk markers. These findings highlight the need for mitigation strategies to facilitate OAT access for this population and for additional harm reduction measures to support AYAs who do not want to use OAT.

Single-nucleus chromatin accessibility and transcriptomic map of breast tissues of women of diverse genetic ancestry

Single-nucleus analysis allows robust cell-type classification and helps to establish relationships between chromatin accessibility and cell-type-specific gene expression. Here, using samples from 92 women of several genetic ancestries, we developed a comprehensive chromatin accessibility and gene expression atlas of the breast tissue. Integrated analysis revealed ten distinct cell types, including three major epithelial subtypes (luminal hormone sensing, luminal adaptive secretory precursor (LASP) and basal-myoepithelial), two endothelial and adipocyte subtypes, fibroblasts, T cells, and macrophages. In addition to the known cell identity genes FOXA1 (luminal hormone sensing), EHF and ELF5 (LASP), TP63 and KRT14 (basal-myoepithelial), epithelial subtypes displayed several uncharacterized markers and inferred gene regulatory networks. By integrating breast epithelial cell gene expression signatures with spatial transcriptomics, we identified gene expression and signaling differences between lobular and ductal epithelial cells and age-associated changes in signaling networks. LASP cells and fibroblasts showed genetic ancestry-dependent variability. An estrogen receptor-positive subpopulation of LASP cells with alveolar progenitor cell state was enriched in women of Indigenous American ancestry. Fibroblasts from breast tissues of women of African and European ancestry clustered differently, with accompanying gene expression differences. Collectively, these data provide a vital resource for further exploring genetic ancestry-dependent variability in healthy breast biology.

Population expansion, larger, and more homogeneous native American ancestry among Mexican mestizo populations based on 10 X-chromosome STR loci (X-STR decaplex system).

To evaluate the genetic diversity, admixture, genetic relationships, and sex-biased demographic processes in Mexican Mestizo (admixed) populations based on 10 X-chromosome STRs (X-STRs). We analyzed the X-STRs Decaplex system in 104 Mexican Native Americans to obtain the ancestral reference needed to complete the demographic analyses above mentioned. We included reported Iberian and Latin American (admixed) populations from Central and South America, as well as datasets from Mexican Mestizos based on Y-linked STRs (Y-STRs), autosomal STRs (A-STRs), and mtDNA. Higher X-linked Native American ancestry was observed among Latin American populations regarding that reported from A-STRs and Y-STRs. The interpopulation differentiation based on ancestry among Mexican Mestizos diminished according to the inheritance pattern: Y-STRs (highest), A-STRs, X-STRs, and mtDNA (lowest). This finding is related to the peculiar admixture process that occurred during and after the Spanish Conquest of Mexico (and most of Latin America), involving a large number of Spanish men (Y-chromosomes) with a lesser proportion of X-chromosomes than autosomes; besides to the limited number of Spanish women (XX) arrived in the Americas in subsequent and shorter periods. Population expansion was detected in Mexican Mestizos from all the country, except those from the southeast region characterized by elevated indigenous ancestry, marginalization, and poorness. Population growth was detected in most Mexican Mestizos, besides more homogeneous and larger Native American ancestry based on X-linked inheritance than that based on autosomal STRs and Y-STRs.

Contesting Indigeneity in Colonial Cuba

Abstract: This article analyzes the differing trajectories of two Indigenous pueblos—Guanabacoa (outside Havana) and Jiguaní (on the outskirts of Bayamo)—to explore the persistence of Native communities in colonial Cuba and various contestations of indigeneity across the longue durée. Though protected Indigenous pueblos were grafted into a larger patchwork of unequal and overlapping republics that formed the building blocks of legal pluralism across the Spanish Americas, they were virtually nonexistent across the Greater Antilles because conquest and colonization had destroyed Native chiefdoms. Consequently, surviving Native communities in the Greater Antilles were suspended between their own claims to Indigenous ancestry and how those with power defined them as an incoherent population. From the sixteenth to the eighteenth century, Spanish officials repeatedly dismissed the authenticity of Native communities on the island, suggesting that they were frauds from the Atlantic world or the vestiges of Indigenous communities that had long ago lost their "Color." Charting these contestations and attending to the formation, composition, and litigiousness of these pueblos demonstrates that indigeneity in Cuba was neither extinguished nor static; it was actively (re)created by a diverse community of indios who used histories rooted in the island's past and legal strategies routed across the Spanish American colonies. This article is accompanied by an appendix on the OI Reader (https://oireader.wm.edu/open_wmq/contesting-indigeneity-in-colonial-cuba/).

Pandemic-related challenges accessing food and primary healthcare among sex workers during the COVID-19 pandemic: findings from a community-based cohort in Vancouver, Canada

IntroductionGlobally, the COVID-19 pandemic upended healthcare services and created economic vulnerability for many. Criminalization of sex work meant sex workers were largely ineligible for Canada’s government-based financial pandemic relief, the Canadian Emergency Response Benefit. Sex workers’ loss of income and inability to access financial support services during the pandemic resulted in many unable to pay rent or mortgage, and in need of assistance with basic needs items including food. Little is known about the unique experiences of sex workers who faced challenges in accessing food during the pandemic and its impact on healthcare access. Thus, we aimed to identify the association between pandemic-related challenges accessing food and primary healthcare among sex workers.MethodsProspective data were drawn from a cohort of women sex workers in Vancouver, Canada (An Evaluation of Sex Workers’ Health Access, AESHA; 2010-present). Data were collected via questionnaires administered bi-annually from October 2020-August 2021. We used univariate and multivariable logistic regression with generalized estimating equations to assess the association between pandemic-related challenges accessing food and challenges accessing primary healthcare over the study period.ResultsOf 170 participants, 41% experienced pandemic-related challenges in accessing food and 26% reported challenges accessing healthcare. Median age was 45 years (IQR:36–53), 56% were of Indigenous ancestry, 86% experienced intimate partner violence in the last six months, and 62% reported non-injection substance use in the last six months. Experiencing pandemic-related challenges accessing food was positively associated with challenges accessing primary healthcare (Adjusted Odds Ratio: 1.99, 95% Confidence Interval: 1.02–3.88) after adjustment for confounders.ConclusionsFindings provide insight about the potential role community-based healthcare delivery settings (e.g., community clinics) can play in ameliorating access to basic needs such as food among those who are highly marginalized. Future pandemic response efforts should also take the most marginalized populations’ needs into consideration by establishing strategies to ensure continuity of essential services providing food and other basic needs. Lastly, policies are needed establishing basic income support and improve access to food resources for marginalized women in times of crisis.