scholarly journals Impact of Genetic Ancestry on Prognostic Biomarkers in Uveal Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3208
Author(s):  
Daniel A. Rodriguez ◽  
Margaret I. Sanchez ◽  
Christina L. Decatur ◽  
Zelia M. Correa ◽  
Eden R. Martin ◽  
...  
Keyword(s):  
Native American ◽  
Uveal Melanoma ◽  
Multiple Testing ◽  
Genetic Ancestry ◽  
Prognostic Biomarkers ◽  
European Ancestry ◽  
Genetic Admixture ◽  
Eqtl Analysis ◽  
Immune Genes ◽  
Global And Local

Uveal melanoma (UM) is the most common cancer of the eye and leads to metastatic death in up to half of patients. Genomic prognostic biomarkers play an important role in clinical management in UM. However, research has been conducted almost exclusively in patients of European descent, such that the association between genetic admixture and prognostic biomarkers is unknown. In this study, we compiled 1381 control genomes from West African, European, East Asian, and Native American individuals, assembled a bioinformatic pipeline for assessing global and local ancestry, and performed an initial pilot study of 141 UM patients from our international referral center that manages many admixed individuals. Global and local estimates were associated with genomic prognostic determinants. Expression quantitative trait loci (eQTL) analysis was performed on variants found in segments. Globally, after correction for multiple testing, no prognostic variable was significantly enriched in a given ancestral group. However, there was a trend suggesting an increased proportion of European ancestry associated with expression of the PRAME oncogene (q = 0.06). Locally enriched European haplotypes were associated with the poor prognosis class 2 gene expression profile and with genes involved in immune regulation (q = 4.7 × 10−11). These findings reveal potential influences of genetic ancestry on prognostic variables, implicate immune genes in prognostic differences based on ancestry, and provide a basis for future studies of admixed patients with UM using rigorous genetic ancestry methodology.

scholarly journals PDTM-33. EUROPEAN GENETIC ANCESTRY ASSOCIATED WITH RISK OF CHILDHOOD EPENDYMOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi194-vi194
Author(s):  
Chenan Zhang ◽  
Quinn Ostrom ◽  
Helen Hansen ◽  
Adam de Smith ◽  
Cassie Kline ◽  
...  
Keyword(s):  
African American ◽  
Native American ◽  
Large Scale ◽  
Genetic Ancestry ◽  
European Ancestry ◽  
Admixture Mapping ◽  
Myxopapillary Ependymoma ◽  
Central Nervous System Tumor ◽  
Molecular Subgroup ◽  
Genome Wide

Abstract BACKGROUND Ependymoma is a histologically-defined central nervous system tumor most commonly occurring in children. Incidence differs by race/ethnicity, with individuals of European ancestry at highest risk. No large-scale genomic analyses of ependymoma predisposition have been conducted to date. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk. METHODS In a multi-ethnic study of Californian children (327 cases, 1970 controls), we estimated the proportions of European, African, and Native American ancestry among admixed Hispanic and African-American subjects and estimated European substructure among non-Hispanic white subjects using genome-wide data. We tested whether genome-wide ancestry differences were associated with ependymoma risk and performed admixture mapping to identify associations with local European ancestry. We also re-analyzed CBTRUS data to examine subtype-specific differences in ependymoma incidence across racial/ethnic groups. RESULTS Each 20% increase in European ancestry was associated with 1.31-fold greater odds of ependymoma among Hispanic and African-American subjects (95% CI: 1.08–1.59, Pmeta=6.7×10–3). Among non-Hispanic whites, European ancestral substructure was also significantly associated with ependymoma risk. Local admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and genotype association analysis in the region identified an association upstream of R-spondin 4 that survived Bonferroni correction (P=2.2x10-5) but was not validated in an independent set of posterior fossa type A (PF-EPN-A) patients. In complementary CBTRUS analyses, American Indian/Alaskan Natives were at reduced risk relative to non-Hispanic whites (RR=0.64, 95% CI:0.46–0.87), as were African-Americans (RR=0.67, 95% CI:0.60–0.74) and Asian/Pacific Islanders (RR=0.86, 95% CI:0.73–1.00). Although overall ependymoma rates were similar in U.S. Hispanics (RR=0.96, 95% CI:0.88–1.05), lower rates were observed for myxopapillary ependymoma and other spinal ependymoma. CONCLUSION Inter-ethnic differences in ependymoma risk vary by histopathologic and potentially molecular subgroup, and are recapitulated in the genomic ancestry of ependymoma patients.

Abstract P152: Do Self-reported Race, Socioeconomic Status And Genetic Ancestry Influence Fasting Glucose? Preliminary Results From the Ongoing Bach Prediabetes Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
James B Meigs ◽  
Gavin Miyasoto ◽  
Bianca Porneala ◽  
Lisa Marceau ◽  
John B McKinlay
Keyword(s):  
Socioeconomic Status ◽  
Native American ◽  
Fasting Glucose ◽  
African Ancestry ◽  
Ethnic Disparities ◽  
Community Dwelling ◽  
Genetic Ancestry ◽  
European Ancestry ◽  
Epidemiologic Survey ◽  
Race Ethnicity

Background: Race/ethnic disparities in type 2 diabetes (T2D) may have both biophysical and social determinants that likely arise before T2D diagnosis. We examined the association of self-reported (SR) race/ethnicity, socioeconomic status (SES) and genetic ancestry with levels of fasting glucose (FG) in individuals not known to have T2D. Methods: The Boston Area Community Health (BACH) Prediabetes study is an ongoing epidemiologic survey of community-dwelling residents of inner-city Boston. A stratified random sample of 3,300 subjects are being drawn from the parent BACH cohort study, recruiting approximately equal numbers in pre-specified age (30–79 years), sex and race/ethnicity groups. Fasting blood is collected, including FG, other health and SES information, during an early AM in-home interview. SES is measured as a standardized composite score of income and education. Genetic ancestry informative markers (AIMs, n=63) that discriminate European, African and Native American continental ancestry are currently available on a random subset. We compared FG levels across groups using ANOVA, testing independent associations of SR race/ethnicity SES using multiple linear regression with significant P=< 0.05. Results: Of 2,933 participants recruited, 63% were women and 70% were older than 50 years. Black, Hispanic and white SR race/ethnicity comprised 32%, 33% and 35% of the sample, respectively. The majority had low SES (57%), 35% had moderate SES and 8% had high SES. FG varied significantly by SR race/ethnicity (mean±SD, mg/dL): 113±37 for white, 119±46 for Hispanic and 121±49 for black subjects (P<0.001). FG was inversely associated with SES (low 122±49, medium 113±39, high 106±23, P<0.001). In joint SR race/ethnicity and SES models adjusting for age and sex, both main effects were attenuated but remained associated with FG (SR race/ethnicity P=0.01; SES P<0.001). For the subsample with AIMs data (n=373), predominant AIMs ancestry, defined as the ancestry most likely as predicted by AIMs, was closely linked to SR race/ethnicity. European ancestry was predominant in 100% of 110 SR white respondents, while African ancestry was predominant in 95% of 129 SR black respondents. In 134 SR Hispanics, 43% were predominantly European, 41% African and 16% Native American. FG varied with predominant AIMs ancestry (European 115±45 mg/dL, African 121±53 and Native American 127±67), although not significantly so (P=0.33), likely due to the limited sample size. Conclusions: Both self-reported race/ethnicity and SES are associated with FG in community-based individuals without known T2D, and they share explanatory information reflecting a common effect. A larger sample with AIMs will help disentangle the degree to which FG variation is socially patterned in the community versus a biophysical phenomenon determined in part by genetic ancestry.

scholarly journals European genetic ancestry associated with risk of childhood ependymoma

2020 ◽  
Vol 22 (11) ◽  
pp. 1637-1646 ◽  
Author(s):  
Chenan Zhang ◽  
Quinn T Ostrom ◽  
Helen M Hansen ◽  
Julio Gonzalez-Maya ◽  
Donglei Hu ◽  
...  
Keyword(s):  
African American ◽  
Native American ◽  
Association Studies ◽  
The United States ◽  
Genetic Ancestry ◽  
European Ancestry ◽  
Admixture Mapping ◽  
Central Nervous System Tumor ◽  
Genome Wide ◽  
Race Ethnicity

Abstract Background Ependymoma is a histologically defined central nervous system tumor most commonly occurring in childhood. Population-level incidence differences by race/ethnicity are observed, with individuals of European ancestry at highest risk. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk in US populations. Methods In a multi-ethnic study of Californian children (327 cases, 1970 controls), we estimated the proportions of European, African, and Native American ancestry among recently admixed Hispanic and African American subjects and estimated European admixture among non-Hispanic white subjects using genome-wide data. We tested whether genome-wide ancestry differences were associated with ependymoma risk and performed admixture mapping to identify associations with local ancestry. We also evaluated race/ethnicity-stratified ependymoma incidence data from the Central Brain Tumor Registry of the United States (CBTRUS). Results CBTRUS data revealed that African American and Native American children have 33% and 36%, respectively, reduced incidence of ependymoma compared with non-Hispanic whites. In genetic analyses, a 20% increase in European ancestry was associated with a 1.31-fold higher odds of ependymoma among self-reported Hispanics and African Americans (95% CI: 1.08–1.59, Pmeta = 6.7 × 10−3). Additionally, eastern European ancestral substructure was associated with increased ependymoma risk in non-Hispanic whites (P = 0.030) and in Hispanics (P = 0.043). Admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and targeted fine-mapping identified a lead variant at rs6039499 near RSPO4 (odds ratio = 1.99; 95% CI: 1.45–2.73; P = 2.2 × 10−5) but which was not validated in an independent set of posterior fossa type A patients. Conclusions Interethnic differences in ependymoma risk are recapitulated in the genomic ancestry of ependymoma patients, implicating regions to target in future association studies.

scholarly journals Heterogeneity of Genetic Admixture Determines SLE Susceptibility in Mexican

2021 ◽  
Vol 12 ◽  
Author(s):  
Susana Hernández-Doño ◽  
Juan Jakez-Ocampo ◽  
José Eduardo Márquez-García ◽  
Daniela Ruiz ◽  
Víctor Acuña-Alonzo ◽  
...  
Keyword(s):  
Native American ◽  
Mexico City ◽  
Lupus Erythematosus ◽  
Population Genetic ◽  
Hla Typing ◽  
European Ancestry ◽  
Genetic Admixture ◽  
Control Group ◽  
Inflammatory Disorder ◽  
Healthy Individuals

Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disorder for which Major Histocompatibility Complex (MHC) genes are well identified as risk factors. SLE patients present different clinical phenotypes, which are partly explained by admixture patterns variation among Mexicans. Population genetic has insight into the high genetic variability of Mexicans, mainly described through HLA gene studies with anthropological and biomedical importance. A prospective, case-control study was performed. In this study, we recruited 146 SLE patients, and 234 healthy individuals were included as a control group; both groups were admixed Mexicans from Mexico City. The HLA typing methods were based on Next Generation Sequencing and Sequence-Based Typing (SBT). The data analysis was performed with population genetic programs and statistical packages. The admixture estimations based on HLA-B and -DRB1 revealed that SLE patients have a higher Southwestern European ancestry proportion (48 ± 8%) than healthy individuals (30 ± 7%). In contrast, Mexican Native American components are diminished in SLE patients (44 ± 1%) and augmented in Healthy individuals (63 ± 4%). HLA alleles and haplotypes’ frequency analysis found variants previously described in SLE patients from Mexico City. Moreover, a conserved extended haplotype that confers risk to develop SLE was found, the HLA-A∗29:02∼C∗16:01∼B∗44:03∼DRB1∗07:01∼DQB1∗02:02, pC = 0.02, OR = 1.41. Consistent with the admixture estimations, the origin of all risk alleles and haplotypes found in this study are European, while the protection alleles are Mexican Native American. The analysis of genetic distances supported that the SLE patient group is closer to the Southwestern European parental populace and farthest from Mexican Native Americans than healthy individuals. Heterogeneity of genetic admixture determines SLE susceptibility and protection in Mexicans. HLA sequencing is helpful to determine susceptibility alleles and haplotypes restricted to some populations.

scholarly journals Genetic admixture patterns in Argentinian Patagonia

2019 ◽  
Author(s):  
María Laura Parolin ◽  
Ulises F Toscanini ◽  
Irina F Velázquez ◽  
Cintia Llull ◽  
Gabriela L Berardi ◽  
...  
Keyword(s):  
Native American ◽  
Latin American ◽  
African Ancestry ◽  
Geographic Origin ◽  
Sub Saharan Africa ◽  
European Ancestry ◽  
Genetic Admixture ◽  
The North ◽  
Sub Saharan ◽  
Different Origins

AbstractAs for other Latin American populations, Argentinians are the result of the admixture amongst different continental groups, mainly from America and Europe, and to a lesser extent from Sub-Saharan Africa. However, it is known that the admixture processes did not occur homogeneously throughout the country. Therefore, considering the importance for anthropological, medical and forensic researches, this study aimed to investigate the population genetic structure of the Argentinian Patagonia, through the analysis of 46 ancestry informative markers, in 433 individuals from five different localities. Overall, in the Patagonian sample, the average individual ancestry was estimated as 35.8% Native American (95% CI: 32.2-39.4%), 62.1% European (58.5-65.7%) and 2.1% African (1.7-2.4%). Comparing the five localities studied, statistically significant differences were observed for the Native American and European contributions, but not for the African ancestry. The admixture results combined with the genealogical information revealed intra-regional variations that are consistent with the different geographic origin of the participants and their ancestors. As expected, a high European ancestry was observed for donors with four grandparents born in Europe (96.8%) or in the Central region of Argentina (85%). In contrast, the Native American ancestry increased when the four grandparents were born in the North (71%) or in the South (61.9%) regions of the country, or even in Chile (60.5%). In summary, our results showed that differences on continental ancestry contribution have different origins in each region in Patagonia, and even in each locality, highlighting the importance of knowing the origin of the participants and their ancestors for the correct interpretation and contextualization of the genetic information.

scholarly journals Genetic ancestry inferred from autosomal and Y chromosome markers and HLA genotypes in Type 1 Diabetes from an admixed Brazilian population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rossana Santiago de Sousa Azulay ◽  
Luís Cristóvão Porto ◽  
Dayse Aparecida Silva ◽  
Maria da Glória Tavares ◽  
Roberta Maria Duailibe Ferreira Reis ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Native American ◽  
Y Chromosome ◽  
Chromosome Analysis ◽  
Brazilian Population ◽  
Genetic Ancestry ◽  
Sample Sizes ◽  
Chromosome Markers ◽  
Hla Genotypes

AbstractThis study aimed to investigate the relationship between genetic ancestry inferred from autosomal and Y chromosome markers and HLA genotypes in patients with Type 1 Diabetes from an admixed Brazilian population. Inference of autosomal ancestry; HLA-DRB1, -DQA1 and -DQB1 typifications; and Y chromosome analysis were performed. European autosomal ancestry was about 50%, followed by approximately 25% of African and Native American. The European Y chromosome was predominant. The HLA-DRB1*03 and DRB1*04 alleles presented risk association with T1D. When the Y chromosome was European, DRB1*03 and DRB1*04 homozygote and DRB1*03/DRB1*04 heterozygote genotypes were the most frequent. The results suggest that individuals from Maranhão have a European origin as their major component; and are patrilineal with greater frequency from the R1b haplogroup. The predominance of the HLA-DRB1*03 and DRB1*04 alleles conferring greater risk in our population and being more frequently related to the ancestry of the European Y chromosome suggests that in our population, the risk of T1D can be transmitted by European ancestors of our process miscegenation. However, the Y sample sizes of Africans and Native Americans were small, and further research should be conducted with large mixed sample sizes to clarify this possible association.

scholarly journals Genetic polymorphisms associated with carotid artery intima-media thickness and coronary artery calcification in women of the Kronos Early Estrogen Prevention Study

2013 ◽  
Vol 45 (2) ◽  
pp. 79-88 ◽  
Author(s):  
Virginia M. Miller ◽  
Tanya M. Petterson ◽  
Elysia N. Jeavons ◽  
Abhinita S. Lnu ◽  
David N. Rider ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Carotid Artery ◽  
Coronary Artery Calcification ◽  
Multiple Testing ◽  
Intima Media Thickness ◽  
Chromosome 17 ◽  
European Ancestry ◽  
P Value ◽  
Prevention Study ◽  
Media Thickness

Menopausal hormone treatment (MHT) may limit progression of cardiovascular disease (CVD) but poses a thrombosis risk. To test targeted candidate gene variation for association with subclinical CVD defined by carotid artery intima-media thickness (CIMT) and coronary artery calcification (CAC), 610 women participating in the Kronos Early Estrogen Prevention Study (KEEPS), a clinical trial of MHT to prevent progression of CVD, were genotyped for 13,229 single nucleotide polymorphisms (SNPs) within 764 genes from anticoagulant, procoagulant, fibrinolytic, or innate immunity pathways. According to linear regression, proportion of European ancestry correlated negatively, but age at enrollment and pulse pressure correlated positively with CIMT. Adjusting for these variables, two SNPs, one on chromosome 2 for MAP4K4 gene (rs2236935, β = 0.037, P value = 2.36 × 10−06) and one on chromosome 5 for IL5 gene (rs739318, β = 0.051, P value = 5.02 × 10−05), associated positively with CIMT; two SNPs on chromosome 17 for CCL5 (rs4796119, β = −0.043, P value = 3.59 × 10−05; rs2291299, β = −0.032, P value = 5.59 × 10−05) correlated negatively with CIMT; only rs2236935 remained significant after correcting for multiple testing. Using logistic regression, when we adjusted for waist circumference, two SNPs (rs11465886, IRAK2, chromosome 3, OR = 3.91, P value = 1.10 × 10−04; and rs17751769, SERPINA1, chromosome 14, OR = 1.96, P value = 2.42 × 10−04) associated positively with a CAC score of >0 Agatston unit; one SNP (rs630014, ABO, OR = 0.51, P value = 2.51 × 10−04) associated negatively; none remained significant after correcting for multiple testing. Whether these SNPs associate with CIMT and CAC in women randomized to MHT remains to be determined.

scholarly journals Differences in MTHFR and LRRK2 variant’s association with sporadic Parkinson’s disease in Mexican Mestizos correlated to Native American ancestry

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Elizabeth Romero-Gutiérrez ◽  
Paola Vázquez-Cárdenas ◽  
Hortensia Moreno-Macías ◽  
José Salas-Pacheco ◽  
Teresa Tusié-Luna ◽  
...  
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Native American ◽  
Neurodegenerative Disorder ◽  
European Ancestry ◽  
Native American Ancestry ◽  
Risk Effect ◽  
Mexican Mestizos ◽  
Shared Risk

AbstractParkinson’s disease (PD), a common neurodegenerative disorder, has a complex etiology where environmental and genetic factors intervene. While a number of genes and variants have been identified in recent decades as causative or protective agents of this condition, a limited number of studies have been conducted in mixed populations, such as Mexican Mestizos. The historical convergence of two founding groups and three ethnicities, and the increasing north-to-south gradient of Native American ancestry in Mexico resulted in a subpopulation structure with considerable genetic diversity. In this work, we investigate the influence of 21 known susceptibility variants for PD. Our case–control study, with a cohort of 311 Mexican Mestizo subjects, found a significant risk association for the variant rs1491942 in LRRK2. However, when stratification by ancestry was performed, a risk effect for MTHFR rs1801133 was observed only in the group with the highest percentage of European ancestry, and the PD risk effect for LRRK2 rs1491942 was significant in subjects with a higher ratio of Native American ancestry. Meta-analyses of these SNP revealed the effect of LRRK2 rs1491942 to be even more significant than previously described in populations of European descent. Although corroboration is necessary, our findings suggest that polymorphism rs1491942 may be useful as a risk marker of PD in Mexican Mestizos with greater Native American ancestry. The absence of associations with the remaining known risk factors is, in itself, a relevant finding and invites further research into the shared risk factors’ role in the pathophysiological mechanisms of this neurodegenerative disorder.

scholarly journals Genetic Ancestry Testing among White Nationalists

2017 ◽  
Author(s):  
Aaron Panofsky ◽  
Joan Donovan
Keyword(s):  
Qualitative Analysis ◽  
Genetic Basis ◽  
Online Discussions ◽  
Genetic Ancestry ◽  
European Ancestry ◽  
Genetic Knowledge ◽  
Data Set ◽  
Genetic Science ◽  
White Nationalism ◽  
Interpretive Framework

Using a data set drawn from the website Stormfront, this paper presents a qualitative analysis of online discussions of white nationalist individuals’ genetic ancestry test (GAT) results. Seeking genetic confirmation of personal identities and having a strong ideology of the genetic basis of race and the value of white “purity,” white nationalists using GATs are sometimes confronted with information they consider evidence of non-white or non-European ancestry. Despite their essentialist views of race, Stormfront posters use GAT information to police individuals’ membership far less commonly than working to develop a variety of scientific and anti-scientific responses enabling them to repair identities by rejecting or reinterpreting GAT results. Simultaneously, however, Stormfront posters use the particular relationships made visible by GATs to debate the collective boundaries and constitution of white nationalism. Bricoleurs with genetic knowledge, white nationalists use a “racial realist” interpretive framework that departs from canons of genetic science but cannot be dismissed simply as ignorant.

scholarly journals Prediction of Eye, Hair and Skin Color in Admixed Populations of Latin America

2020 ◽  
Author(s):  
Sagnik Palmal ◽  
Kaustubh Adhikari ◽  
Javier Mendoza-Revilla ◽  
Macarena Fuentes-Guajardo ◽  
Caio C. Silva de Cerqueira ◽  
...  
Keyword(s):  
Native American ◽  
Skin Color ◽  
Prediction Accuracy ◽  
Prediction Models ◽  
Skin Pigmentation ◽  
Genetic Ancestry ◽  
Learning Approaches ◽  
Latin Americans ◽  
Eye Color ◽  
The Impact

AbstractWe report an evaluation of prediction accuracy for eye, hair and skin pigmentation based on genomic and phenotypic data for over 6,500 admixed Latin Americans (the CANDELA dataset). We examined the impact on prediction accuracy of three main factors: (i) The methods of prediction, including classical statistical methods and machine learning approaches, (ii) The inclusion of non-genetic predictors, continental genetic ancestry and pigmentation SNPs in the prediction models, and (iii) Compared two sets of pigmentation SNPs: the commonly-used HIrisPlex-S set (developed in Europeans) and novel SNP sets we defined here based on genome-wide association results in the CANDELA sample. We find that Random Forest or regression are globally the best performing methods. Although continental genetic ancestry has substantial power for prediction of pigmentation in Latin Americans, the inclusion of pigmentation SNPs increases prediction accuracy considerably, particularly for skin color. For hair and eye color, HIrisPlex-S has a similar performance to the CANDELA-specific prediction SNP sets. However, for skin pigmentation the performance of HIrisPlex-S is markedly lower than the SNP set defined here, including predictions in an independent dataset of Native American data. These results reflect the relatively high variation in hair and eye color among Europeans for whom HIrisPlex-S was developed, whereas their variation in skin pigmentation is comparatively lower. Furthermore, we show that the dataset used in the training of prediction models strongly impacts on the portability of these models across Europeans and Native Americans.

Sign in / Sign up

Export Citation Format

Share Document