Association Of African Ancestry Research Articles

Association of the genetic ancestry with resistant hypertension in the ReHOT (Resistant Hypertension Optimal Treatment) randomized study

Resistant hypertension (RH) is defined as uncontrolled blood pressure despite treatment with three or more antihypertensive medications, including, if tolerated, a diuretic in adequate doses. It has been widely known that race is associated with blood pressure control. However, intense debate persists as to whether this is solely explained by unadjusted socioeconomical variables or genetic variation. In this scenario, the main aim was to evaluate the association between genetic ancestry and resistant hypertension in a large sample from a multicenter trial of stage II hypertension, the ReHOT study. Samples from 1,358 patients were analyzed, of which 167 were defined as resistant hypertensive. Genetic ancestry was defined using a panel of 192 polymorphic markers. The genetic ancestry was similar in resistant (52.0% European, 36.7% African and 11.3% Amerindian) and nonresistant hypertensive patients (54.0% European, 34.4% African and 11.6% Amerindian) (p > 0.05). However, we observed a statistically suggestive association of African ancestry with resistant hypertension in brown patient group. In conclusion, increased African genetic ancestry was not associated with RH in Brazilian patients from a prospective randomized hypertension clinical trial.

Association of African Ancestry With Electrocardiographic Voltage and Concentric Left Ventricular Hypertrophy

Compared with white individuals, black individuals have increased electrocardiographic voltage and an increased prevalence of concentric left ventricular (LV) hypertrophy. Whether environmental or genetic factors lead to these racial differences is unknown. To determine whether proportion of genetically determined African ancestry among self-reported black individuals is associated with increased electrocardiographic voltage and concentric LV hypertrophy (LVH). The Dallas Heart Study is a probability-based cohort study of English- or Spanish-speaking Dallas County, Texas, residents, with deliberate oversampling of black individuals. Participants underwent extensive phenotyping, which included electrocardiography (ECG), cardiac magnetic resonance imaging (CMR), and dual-energy radiography absorptiometry (DEXA) at a single center. Participants aged 18 to 65 years who enrolled in the Dallas Heart Study between July 2000 and December 2002, self-identified as black (n = 1251) or white (n = 826), and had ECG, CMR, and DEXA data were included in this analysis. Data were analyzed from June 2017 to September 2018. Proportion of African ancestry. Electrocardiographic voltage (12-lead and 9-lead) and markers of concentric LVH as assessed by CMR (LV concentricity0.67 [LV mass/end-diastolic volume0.67], LV wall thickness [LVWT], and prevalent LVH [defined by LV mass/height2.7]). Of the 2077 participants included in the study, 1138 (54.8%) were women, and the mean (SD) age was 45.2 (9.9) years. Black race and African ancestry were individually associated with increased ECG voltage, LV concentricity0.67, LVWT, and prevalent LVH in multivariable analyses adjusting for age, sex, systolic blood pressure, antihypertensive medication use, and body composition. When African ancestry and black race were entered together into multivariable models, African ancestry but not black race remained associated with ECG voltage, LVWT, LV concentricity0.67, and prevalent LVH. Among black participants, African ancestry remained associated with these 4 phenotypes (12-lead voltage: β, 0.05; P = .04; LVWT: β, 0.05; P = .02; LV concentricty0.67: β, 0.05; P = .045; prevalent LVH: odds ratio, 1.2; 95% CI, 1.03-1.4; P = .02). Genetically determined African ancestry was associated with electrocardiographic voltage, measures of concentric LV remodeling, and prevalent LVH. These data support a genetic basis related to African ancestry for the increased prevalence of these cardiovascular traits in black individuals.

Abstract 4840: TGFBR1 and TP53 SNPs interactions associated with colorectal cancer risk: Analysis of metabolic pathways using a Random Forest approach.

Abstract Background: We recently found the association of african ancestry with colorrectal cancer risk in Colombian population. Currently due to sample size limitations we can not perform further analysis (ej.GWAS) to explore this finding. Pathway analysis has been proposed as a complementary approach to single SNP analyses in GWAS, specially in hypothesis driven analysis. AIM: To evaluate the association of SNP included in the SNP500 cancer with colorectal cancer risk in colombian population. Methods: We recruited 264 controls and 203 colorectal cancer cases from 5 Colombian cities.Participants gave written informed consent, donated blood samples and answered guided-questionnaires. SNP analysis was done using and high reliable comertial plataform the Illumina Cancer Panel This panel includes 1492 SNP related to different cancer metabolic pathways and were drawn from the SNP500 cancer database. After QC procedures we grouped these SNP according to the pathway maps reported in the KEGG database. Using a Random Forest Analysis we evaluate the discriminative capacity between cancer case and control of each SNP in each pathway separately. Age sex and african ancestry where considered covariates for this analysis. Those SNPs showing a better o similar performance to african ancestry were further analyzed in a conditional logistic regression model, where all known risk factors for colorectal cancer were included. Results: 1192 SNPs and 418 individuals pass through the QC protocol. SNP were grouped in 16 different pathways. Random Forest analysis showed that only 1 pathway, the hsa05210 (i.e colorrectal cancer) contained 2 SNPs, rs868 and rs2909430, that outperformed the discriminatory capacity of african ancestry between cases and controls. Conditional logistic regression analysis showed an interaction between both polymorphisms (p<0.001). Compared against carriers of the mayor alleles of these two SNPs, we found a protective effect against colorectal cancer risk among carriers of only one of the variants (OR 0.04 CI95% 0.01-0.25 and OR 0.26 CI95% 0.12-.053 for rs868 and rs2909430 respectively). In contrast we found a positive association with cancer risk among carriers of both variants (OR 12.5 CI95% 3.15-49-98). African ancestry possitive association remained significant in the multiple regression analysis (p<0.01). Rs868 and rs2909430 are located in TP53 and TGFBR1 genes. Other Polymorphisms in this genes has shown conflicting results in previous analysis on colorectal cancer risk. Conclusion: We report for the first time an epistatic effect between two polymorphism located in genes involved in the colorectal cancer metabolic pathway in an admixed population after controlling for population structure and known risk factors. These results may help to explain the diverging results observed in studies of the association of these genes with colorectal cancer risk Citation Format: Gustavo Hernandez-Suarez, MariaCarolina Sanabria, Martha Serrano, Jovanny Zabaleta, Albert Tenesa. TGFBR1 and TP53 SNPs interactions associated with colorectal cancer risk: Analysis of metabolic pathways using a Random Forest approach. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4840. doi:10.1158/1538-7445.AM2013-4840 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.

African Ancestry is a Risk Factor for Asthma and High Total IgE Levels in African Admixed Populations

Characterization of genetic admixture of populations in the Americas and the Caribbean is of interest for anthropological, epidemiological, and historical reasons. Asthma has a higher prevalence and is more severe in populations with a high African component. Association of African ancestry with asthma has been demonstrated. We estimated admixture proportions of samples from six trihybrid populations of African descent and determined the relationship between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 237 ancestry informative markers in asthmatics and nonasthmatic controls from Barbados (190/277), Jamaica (177/529), Brazil (40/220), Colombia (508/625), African Americans from New York (207/171), and African Americans from Baltimore/Washington, D.C. (625/757). We estimated individual ancestries and evaluated genetic stratification using Structure and principal component analysis. Association of African ancestry and asthma and tIgE was evaluated by regression analysis. Mean ± SD African ancestry ranged from 0.76 ± 0.10 among Barbadians to 0.33 ± 0.13 in Colombians. The European component varied from 0.14 ± 0.05 among Jamaicans and Barbadians to 0.26 ± 0.08 among Colombians. African ancestry was associated with risk for asthma in Colombians (odds ratio (OR) = 4.5, P = 0.001) Brazilians (OR = 136.5, P = 0.003), and African Americans of New York (OR: 4.7; P = 0.040). African ancestry was also associated with higher tIgE levels among Colombians (β = 1.3, P = 0.04), Barbadians (β = 3.8, P = 0.03), and Brazilians (β = 1.6, P = 0.03). Our findings indicate that African ancestry can account for, at least in part, the association between asthma and its associated trait, tIgE levels.

Abstract A84: Race, neighborhood socioeconomic characteristics, and Helicobacter pylori seroprevalence

Abstract Background: Recently, very high Helicobacter pylori sero-prevalence rates were found among African Americans, especially those of higher percentage of African ancestry, residing in the southeastern US. We sought to determine if neighborhood-level socio-economic characteristics, above and beyond individual-level socio-economic characteristics, are associated with Helicobacter pylori prevalence, and, if so, if this helps to explain the strong association with African ancestry. Methods: Antibodies to Helicobacter pylori proteins were assessed in the serum of 665 African American and white participants from the Southern Community Cohort Study. African and European admixture was estimated using a panel of 276 ancestry genetic markers. Prevalence odds ratios for CagA-specific Helicobacter pylori status associated with10 block-level measures of socio-economic status, obtained from linkage to the US Census, were calculated using polytomous logistic regression. Results: After adjusting for individual-level socio-economic characteristics, three neighborhood-level characteristics were significantly inversely related to CagA+ Helicobacter pylori sero-positivity: percent adults completed high school; median value of owner-occupied houses; and percent employed (comparing highest tertile to lowest tertile, OR=0.47, 95%CI: 0.26–0.85; OR=0.56, 95% CI: 0.32–0.99; and OR=0.59, 95% CI: 0.34–1.03, respectively). However, inclusion of these neighborhood-level measures did not attenuate the association of African ancestry and CagA+ Helicobacter pylori sero-prevalence, with African Americans of low, medium, and high African ancestry maintaining 2-, 7-, and 9-fold increased odds compared to whites. Neighborhood levels of education, house values, and employment are associated with sero-prevalence to CagA+Helicobacter pylori, highlighting high-risk areas for prevention and screening efforts, but the strong relationship between African ancestry level and CagA+ Helicobacter pylori sero-prevalence persisted after adjustment for individual and neighborhood-level socio-economic characteristics, suggesting a biological basis for this association. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A84.

The Association of African Ancestry and Elevated Creatinine in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Whether genetic factors account for differences in early kidney disease among blacks in a young healthy population is not well known. We evaluated the association of self-reported race and genetic African ancestry with elevated creatinine (≧1.3 mg/dl for men, ≧1.1 mg/dl for women) among 3,113 black and white participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, ages 38–50 years. We estimated individual African ancestry using 42 ancestry informative markers. Blacks were more likely to have elevated creatinine than whites, and this effect was more pronounced in men: adjusted odds ratio (AOR) for black versus white men = 7.03, 4.15–11.91; AOR for women = 2.40, 1.15–5.02. Higher African ancestry was independently associated with elevated creatinine among black men (AOR = 1.53,1.08–2.16 per SD increase in African ancestry), but not women. A graded increase in odds of elevated creatinine by African Ancestry was observed among black men compared with white men: AOR = 4.27 (2.26–10.06) for black men with 40–70% African ancestry; AOR = 8.09 (4.19–15.61) for black men with 70–80% African ancestry; AOR = 9.05 (4.81–17.02) for black men with >80% African ancestry. Genetic factors common to African ancestry may be associated with increased risk of early kidney dysfunction in a young, healthy population, particularly among black men.