Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer
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PROVIDER: PRJNA913422 | ENA |
REPOSITORIES: ENA
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Project description:The genomic and immune landscapes of prostate cancer differ by self-identified race. However, few studies have examined the genome-wide copy number landscape and immune content of matched cohorts with genetic ancestry data and clinical outcomes. Here, we assessed prostate cancer somatic copy number alterations (sCNA) and tumor immune content of a grade-matched, surgically-treated cohort of 145 self-identified Black (BL) and 145 self-identified white (WH) patients with genetic ancestry estimation. A generalized linear model adjusted with age, pre-operative PSA, and Grade Group and filtered for germline copy number variations (gCNV) identified 143 loci where copy number varied significantly by percent African ancestry, clustering on chromosomes 6p, 10q, 11p, 12p, and 17p. Multivariable Cox regression models adjusted for age, pre-operative PSA levels, and Grade Group revealed that chromosome 8q gains (including MYC) were significantly associated with biochemical recurrence and metastasis, independent of genetic ancestry. Finally, regulatory T-cell density in BL and WH patients was significantly correlated with percent genome altered, and these findings were validated in the TCGA cohort. Taken together, our findings identify specific sCNA linked to genetic ancestry and outcome in primary prostate cancer and demonstrate that regulatory T-cell infiltrate varies by global sCNA burden in primary disease.
2023-05-31 | GSE221219 | GEO
Project description:The genomic and immune landscapes of prostate cancer differ by self-identified race. However, few studies have examined the genome-wide copy number landscape and immune content of matched cohorts with genetic ancestry data and clinical outcomes. Here, we assessed prostate cancer somatic copy number alterations (sCNA) and tumor immune content of a grade-matched, surgically treated cohort of 145 self-identified Black (BL) and 145 self-identified White (WH) patients with genetic ancestry estimation. A generalized linear model adjusted with age, preoperative prostate-specific antigen (PSA), and Gleason Grade Group and filtered for germline copy number variations (gCNV) identified 143 loci where copy number varied significantly by percent African ancestry, clustering on chromosomes 6p, 10q, 11p, 12p, and 17p. Multivariable Cox regression models adjusted for age, preoperative PSA levels, and Gleason Grade Group revealed that chromosome 8q gains (including MYC) were significantly associated with biochemical recurrence and metastasis, independent of genetic ancestry. Finally, Treg density in BL and WH patients was significantly correlated with percent genome altered, and these findings were validated in the TCGA cohort. Taken together, our findings identify specific sCNA linked to genetic ancestry and outcome in primary prostate cancer and demonstrate that Treg infiltration varies by global sCNA burden in primary disease.
| S-EPMC9977441 | biostudies-literature
Project description:Characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step to connect patient ancestry with molecular disease pathogenesis. Nonsynonymous single nucleotide polymorphisms (SNPs) encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs), were prioritized from 1000 genomes. In silico analysis shows that as few as 20 pAIMs can determine ancestry proportions similarly to >260K SNPs (R2=0.9905). Multiplexed proteomic analysis of >100 human endometrial cancer cell lines and uterine leiomyoma (ULM) tissues combined resulted in the quantitation of 62 pAIMs that correlate with self-described race and genotype-confirmed patient ancestry. Candidates include a D451E substitution in GC vitamin D-binding protein previously associated with altered vitamin D levels in African and European populations. These efforts describe a generalized set of markers for proteoancestry assessment that will further support studies investigating the impact of ancestry on the human proteome and how this relates to the pathogenesis of uterine neoplasms.
2022-02-16 | PXD029323 | Pride
Project description:Large-scale multi-ethnic cohorts offer unprecedented opportunities to elucidate the genetic factors influencing complex traits related to health and disease among minority populations. At the same time, the genetic diversity in these cohorts presents new challenges for analysis and interpretation. We consider the utility of race and/or ethnicity categories in genome-wide association studies (GWASs) of multi-ethnic cohorts. We demonstrate that race/ethnicity information enhances the ability to understand population-specific genetic architecture. To address the practical issue that self-identified racial/ethnic information may be incomplete, we propose a machine learning algorithm that produces a surrogate variable, termed HARE. We use height as a model trait to demonstrate the utility of HARE and ethnicity-specific GWASs.
| S-EPMC6817526 | biostudies-literature
Project description:Background: Differences in breast cancer outcomes according to race/ethnicity have been reported. Hispanic/Latino (H/L) populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. Some studies suggest that breast cancer-specific mortality is higher in U.S. Hispanic/Latinas compared to non-Hispanic Whites (NHW) even after adjustment for socioeconomic status and education. The molecular profile of breast cancer has been widely described in NHWs but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian H/L women was Luminal B as defined by surrogate St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. Methods: We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. Results: We found 5 genes potentially modulated by genetic ancestry: ERBB2 (Fold Change = 2.367, padj < 0.01), GRB7 (Fold Change = 2.327, padj < 0.01), GSDMB (Fold Change = 1.723, padj < 0.01, MIEN1 (Fold Change = 2.195, padj < 0.01 and ONECUT2 (Fold Change = 2.204, padj < 0.01). In the replication set we found a statistical significant association between European ancestry fraction and the expression levels of ERBB2 (p = 0.02, B = 2.49) and ONECUT2 (p = 0.04, B = -4.87). We also observed statistical significant associations for ERBB2 expression with Indigenous American ancestry (p < 0.001, B = 3.82). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. Conclusions: Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value.
2017-10-04 | GSE101927 | GEO
Project description:Women of sub-Saharan African descent have disproportionately higher incidence of Triple Negative Breast Cancer (TNBC), and TNBC-specific mortality. Population comparative studies show racial differences in TNBC biology, including higher prevalence of basal-like and Quadruple-Negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily United States (US) populations. Due to heterogenous genetic admixture, and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNAseq on an international cohort of AAs, west and east Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed tumor-associated immunological profiles are distinct in patients of African descent.
2022-11-09 | GSE211167 | GEO
Project description:The green algal Botryococcus braunii (Chlorophyte) is known for accumulating high levels of hydrocarbons that are a useful alternative to fossil fuels. B. braunii is categorized into three groups based on types of their accumulated hydrocarbons: alkadiene/triene in race A, botryococcenes in race B, and lycopadiene in race L. Transcriptomic studies in race A and race B have discovered tremendous information related to the genes encoding proteins involved in hydrocarbon biosynthesis. However, transcriptome of race L has not been reported. In this study, we report a transcriptome of race L B. braunii AC768 through the de novo assembly using Hiseq platform. Our analyses indicate that photosynthesis and protein biosynthesis are the most abundantly transcribed in actively growing race L B. braunii. We show that the transcriptome of race L shares similar amounts (~20%) of mutual best-hits with that of race A or race B. Sequence homologous analyses indicate that enzymes involved in squalene and phytoene biosynthesis are well separated into geranyl-diphosphate synthase, farnesyl-diphosphate synthase, geranylgeranyl-diphosphate synthase, phytoene synthase, and squalene synthase. Both B. braunii specific enzymes botryococcene synthase SSL3 and lycopaoctaene synthase LOS are found to form distinctive subgroups in the group of squalene synthase. One of the ESTs in AC768 transcriptome that falls into the subgroup with LOS and shares >88% identity with that of LOS. Together, our results show that SSL and LOS are unique to race B and race L B. braunii subspecies, respectively. We propose that phytoene synthase in race L shares higher homolog to squalene synthase than phytoene synthase in other algae.
2019-11-21 | GSE96585 | GEO
Project description:BackgroundMany allergic conditions occur more frequently in African American patients when compared with white patients; however, it is not known whether this represents genetic predisposition or disparate environmental exposures.ObjectiveWe sought to assess the relationship of self-reported race and genetic ancestry to allergic sensitization.MethodsWe included 601 women enrolled in a population-based cohort study whose self-reported race was African American or white. Genetic ancestry was estimated by using markers that differentiate West African and European ancestry. We assessed the relationship between allergic sensitization (defined as > or =1 allergen-specific IgE results) and both self-reported race and genetic ancestry. Regression models adjusted for sociodemographic variables, environmental exposures, and location of residence.ResultsThe average proportion of West African ancestry in African American participants was 0.69, whereas the mean proportion of European ancestry in white participants was 0.79. Self-reported African American race was associated with allergic sensitization when compared with those who reported being white (adjusted odds ratio, 2.19; 95% CI, 1.22-3.93), even after adjusting for other variables. Genetic ancestry was not significantly associated with allergic sensitization after accounting for location of residence (adjusted odds ratio, 2.09 for urban vs suburban residence; 95% CI, 1.32-3.31).ConclusionSelf-reported race and location of residence appeared to be more important predictors of allergic sensitization when compared with genetic ancestry, suggesting that the disparity in allergic sensitization by race might be primarily a result of environmental factors rather than genetic differences.
| S-EPMC2951327 | biostudies-literature
Project description:Individuals of African descent in the United States suffer disproportionately from diseases with a metabolic etiology (obesity, metabolic syndrome, and diabetes), and from the pathological consequences of these disorders (hypertension and cardiovascular disease). Using a combination of genetic/genomic and bioinformatics approaches, we identified a large number of genes that were both differentially expressed between American subjects self-identified to be of either African or European ancestry and that also contained single nucleotide polymorphisms that distinguish distantly related ancestral populations. Several of these genes control the metabolism of simple carbohydrates and are direct targets for the SREBP1, a metabolic transcription factor also differentially expressed between our study populations. These data support the concept of stable patterns of gene transcription unique to a geographic ancestral lineage. The coordinated transcriptional adaptation of carbohydrate metabolism to dietary environmental pressures suggests a genetic and transcriptional mechanism for the disproportionate levels of obesity, diabetes, and cardiovascular disease observed in Americans with African ancestry. Keywords: Ancestry-dependent gene expression, functional genomics, personalized medicine, multi-factoral disease, nutrition, diabetes
2009-10-31 | GSE12959 | GEO
Project description:A population and admixture analysis of Mesoamerican Totonacs and South American Bolivians. A panel of highly informative ancestry informative markers (AIMs) for New World populations is identified. Regions coinciding with AIMs are have moderate signatures of selection. Population structure and differentiation were assessed with a genome-wide panel of 815,377 autosomal markers, Y-chromosome STR and SNPs, and mtDNA sequence data.
2011-06-09 | E-GEOD-29851 | biostudies-arrayexpress