Associations between genome-wide Native American ancestry, known risk alleles and B-cell ALL risk in Hispanic children.
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ABSTRACT:
SUBMITTER: Walsh KM
PROVIDER: S-EPMC3864612 | biostudies-literature | 2013 Dec
REPOSITORIES: biostudies-literature
Publications
Associations between genome-wide Native American ancestry, known risk alleles and B-cell ALL risk in Hispanic children.
Walsh K M KM Chokkalingam A P AP Hsu L-I LI Metayer C C de Smith A J AJ Jacobs D I DI Dahl G V GV Loh M L ML Smirnov I V IV Bartley K K Ma X X Wiencke J K JK Barcellos L F LF Wiemels J L JL Buffler P A PA
Leukemia 20130425 12
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Project description:RationaleGene promoter methylation detected in sputum predicts lung cancer risk in smokers. Compared with non-Hispanic whites (NHW), Hispanics have a lower age-standardized incidence for lung cancer.ObjectivesThis study compared the methylation prevalence in sputum of NHWs with Hispanics using the Lovelace Smokers cohort (n = 1998) and evaluated the effect of Native American ancestry (NAA) and diet on biomarkers for lung cancer risk.MethodsGenetic ancestry was estimated using 48 ancestry markers. Diet was assessed by the Harvard University Dietary Assessment questionnaire. Methylation of 12 genes was measured in sputum using methylation-specific polymerase chain reaction. The association between NAA and risk for methylation was assessed using generalized estimating equations. The ethnic difference in the association between pack-years and risk for lung cancer was assessed in the New Mexico lung cancer study.Measurements and main resultsOverall Hispanics had a significantly increased risk for methylation across the 12 genes analyzed (odds ratio, 1.18; P = 0.007). However, the risk was reduced by 32% (P = 0.032) in Hispanics with high versus low NAA. In the New Mexico lung cancer study, Hispanic non-small cell lung cancer cases have significantly lower pack-years than NHW counterparts (P = 0.007). Furthermore, compared with NHW smokers, Hispanic smokers had a more rapidly increasing risk for lung cancer as a function of pack-years (P = 0.058).ConclusionsNAA may be an important risk modifier for methylation in Hispanic smokers. Smoking intensity may have a greater impact on risk for lung cancer in Hispanics compared with NHWs.
| S-EPMC3863742 | biostudies-literature
Project description:Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1-4.3%, P = 6×10-27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data.
| S-EPMC5444600 | biostudies-literature
Project description: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.
| S-EPMC11759616 | biostudies-literature
Project description:The cytochrome p450 family 19 gene (CYP19A1) encodes for aromatase, which catalyzes the final step in estrogen biosynthesis and conversion of androgens to estrogens. Genetic variation in CYP19A1 is linked to higher circulating estrogen levels and increased aromatase expression. Using data from the Breast Cancer Health Disparities Study, a consortium of three population-based case-control studies in the United States (n = 3,030 non-Hispanic Whites; n = 2,893 Hispanic/Native Americans (H/NA) and Mexico (n = 1,810), we examined influence of 25 CYP19A1 tagging single-nucleotide polymorphisms (SNPs) on breast cancer risk and mortality, considering NA ancestry. Odds ratios (ORs) and 95 % confidence intervals (CIs) and hazard ratios estimated breast cancer risk and mortality. After multiple comparison adjustment, none of the SNPs were significantly associated with breast cancer risk or mortality. Two SNPs remained significantly associated with increased breast cancer risk in women of moderate to high NA ancestry (≥29 %): rs700518, ORGG 1.36, 95 % CI 1.11-1.67 and rs11856927, ORGG 1.35, 95 % CI 1.05-1.72. A significant interaction was observed for rs2470144 and menopausal status (p adj = 0.03); risk was increased in postmenopausal (ORAA 1.22, 95 % CI 1.05-1.14), but not premenopausal (ORAA 0.78, 95 % CI 0.64-0.95) women. The absence of an overall association with CYP19A1 and breast cancer risk is similar to previous literature. However, this analysis provides support that variation in CYP19A1 may influence breast cancer risk differently in women with moderate to high NA ancestry. Additional research is warranted to investigate the how variation in an estrogen-regulating gene contributes to racial/ethnic disparities in breast cancer.
| S-EPMC4435673 | biostudies-literature
Project description: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.
| S-EPMC10544431 | biostudies-literature
Project description:Higher body mass index (BMI) is a well-established risk factor for type 2 diabetes, and rates of obesity and type 2 diabetes are substantially higher among Mexican-Americans relative to non-Hispanic European Americans. Mexican-Americans are genetically diverse, with a highly variable distribution of Native American, European, and African ancestries. Here, we evaluate the role of Native American ancestry on BMI and diabetes risk in a well-defined Mexican-American population. Participants were randomly selected among individuals residing in the Houston area who are enrolled in the Mexican-American Cohort study. Using a custom Illumina GoldenGate Panel, we genotyped DNA from 4,662 cohort participants for 87 Ancestry-Informative Markers. On average, the participants were of 50.2% Native American ancestry, 42.7% European ancestry and 7.1% African ancestry. Using multivariate linear regression, we found BMI and Native American ancestry were inversely correlated; individuals with <20% Native American ancestry were 2.5 times more likely to be severely obese compared to those with >80% Native American ancestry. Furthermore, we demonstrated an interaction between BMI and Native American ancestry in diabetes risk among women; Native American ancestry was a strong risk factor for diabetes only among overweight and obese women (OR = 1.190 for each 10% increase in Native American ancestry). This study offers new insight into the complex relationship between obesity, genetic ancestry, and their respective effects on diabetes risk. Findings from this study may improve the diabetes risk prediction among Mexican-American individuals thereby facilitating targeted prevention strategies.
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Project description:Currently, little is known about patterns of co-occurring risk and protective factors among young children. Understanding variations in co-occurring risk and protective factors among children in Alaska is important as experiences of collective trauma may contribute to differences in the intersection of risk and protective factors between Alaska Native/American Indian (AN/AI) and non-Native children. Using data from the Alaska Longitudinal Child Abuse and Neglect Linkage (ALCANLink) project, a linkage of the 2009-2011 Alaska Pregnancy Risk Assessment Monitoring System survey and administrative data sources, and the 2012-2014 Childhood Understanding Behaviors Survey, we conducted latent class analysis to identify classes of AN/AI (N = 593) and non-Native (N = 1018) children in terms of seven risk factors (poverty, maternal depression, maternal binge drinking, parental incarceration, intimate partner violence exposure, other violence exposure, child maltreatment) and four protective factors (father figure involvement, reading by adults, family meals, peer interactions) experienced prior to age 3 years. We identified two classes among AN/AI children: (1) high risk-moderate protection (29.1%) and (2) low socioeconomic status-high protection (70.9%). We identified two classes among non-Native children: (1) moderate risk-high protection (32.9%) and (2) low risk-high protection (67.1%). A test of invariance revealed that risk and protective factor probabilities differed significantly for corresponding classes of AN/AI and non-Native children. Overall, results demonstrate heterogeneity within and between AN/AI and non-Native children in early experiences of risk and protection and suggest that interventions will be more effective if tailored to the experiences and developmental needs of specific groups of Alaska children.
| S-EPMC7364379 | biostudies-literature
Project description:BackgroundWhether Native American ancestry (NAA) is associated with COPD or lung function in a racially admixed Hispanic population is unknown.MethodsWe recruited 578 Costa Ricans with and without COPD into a hybrid case-control/family-based cohort, including 316 members of families of index case subjects. All participants completed questionnaires and spirometry and gave a blood sample for DNA extraction. Genome-wide genotyping was conducted with the Illumina Human610-Quad and HumanOmniExpress BeadChip kits (Illumina Inc), and individual ancestral proportions were estimated from these genotypic data and reference panels. For unrelated individuals, linear or logistic regression was used for the analysis of NAA and COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stage II or greater) or lung function. For extended families, linear mixed models and generalized estimating equations were used for the analysis. All models were adjusted for age, sex, educational level, and smoking behavior; models for FEV1 were also adjusted for height.ResultsThe average proportion of European, Native American, and African ancestry among participants was 62%, 35%, and 3%, respectively. After adjustment for current smoking and other covariates, NAA was inversely associated with COPD (OR per 10% increment, 0.55; 95% CI, 0.41-0.75) but positively associated with FEV1, FVC, and FEV1/FVC. After additional adjustment for pack-years of smoking, the association between NAA and COPD or lung function measures was slightly attenuated. We found that about 31% of the estimated effect of NAA on COPD is mediated by pack-years of smoking.ConclusionsNAA is inversely associated with COPD but positively associated with FEV1 or FVC in Costa Ricans. Ancestral effects on smoking behavior partly explain the findings for COPD but not for FEV1 or FVC.
| S-EPMC3971968 | biostudies-literature
Project description:We evaluated the genome-wide mRNA expression profiles in lymphoblastoid cell lines of familial ovarian cancer patients and controls
2013-06-06 | GSE37582 | GEO
Project description:We evaluated the genome-wide mRNA expression profiles in lymphoblastoid cell lines of familial ovarian cancer patients and controls Comparing the mRNA expression data of 74 ovarian cancer cases with 47 healthy controls. Genotype information of the 7 risk alleles is linked to the bottom of the Series record.
2013-06-06 | E-GEOD-37582 | biostudies-arrayexpress