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Meta-analysis of the efficacy and safety of non-vitamin K antagonist oral anticoagulants with warfarin in Latin American patients with atrial fibrillation.
Su, Z, Zhang, H, He, W, Ma, J, Zeng, J, Jiang, X
Medicine. 2020;(18):e19542
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Abstract
BACKGROUND Data of non-vitamin K antagonist oral anticoagulants (NOACs) in current management of atrial fibrillation (AF) are predominantly derived from North American and European regions. However, the effects of NOACs for stroke prevention in Latin America remain unclear. Therefore, we aimed to compare the efficacy and safety of NOACs with warfarin in Latin American patients with AF. METHODS The PubMed and Embase databases were systematically searched until July 12, 2019 for applicable randomized clinical trials. The risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model. RESULTS Four trials involving 8943 Latin American patients were included in this meta-analysis. In anticoagulated patients with AF, Latin American patients had higher rates of stroke or systemic embolism and all-cause death compared with non-Latin American subjects. Compared with warfarin use, the use of NOACs was significantly associated with reduced risks of stroke or systemic embolism, major bleeding, intracranial bleeding, and any bleeding in Latin American patients. There were no significant differences in the risks of ischemic stroke, all-cause death, and gastrointestinal bleeding between Latin and non-Latin American groups. All the interactions between Latin and non-Latin American groups about efficacy and safety outcomes of NOACs compared with warfarin were non-significant (all Pinteraction > .05). CONCLUSIONS Our meta-analysis suggested that the use of NOACs was at least non-inferior to warfarin use for stroke prevention in Latin American patients with AF.
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An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos.
Gignoux, CR, Torgerson, DG, Pino-Yanes, M, Uricchio, LH, Galanter, J, Roth, LA, Eng, C, Hu, D, Nguyen, EA, Huntsman, S, et al
The Journal of allergy and clinical immunology. 2019;(3):957-969
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Abstract
BACKGROUND Asthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies. OBJECTIVE We sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility. METHODS We leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups. RESULTS We identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P = 6.8 × 10-6), where Native American ancestry was associated with increased risk of asthma (odds ratio [OR], 1.20; 95% CI, 1.07-1.34; P = .002) and European ancestry was associated with protection (OR, 0.86; 95% CI, 0.77-0.96; P = .008). Our findings were replicated in an independent childhood asthma study in Latinos (P = 5.3 × 10-3, combined P = 2.6 × 10-7). Fine mapping of 18q21 in 1978 Latinos identified a significant association with multiple variants 5' of SMAD family member 2 (SMAD2) in Mexicans, whereas a single rare variant in the same window was the top association in Puerto Ricans. Low versus high SMAD2 blood expression was correlated with case status (13.4% lower expression; OR, 3.93; 95% CI, 2.12-7.28; P < .001). In addition, lower expression of SMAD2 was associated with more frequent exacerbations among Puerto Ricans with asthma. CONCLUSION Ancestry at 18q21 was significantly associated with asthma in Latinos and implicated multiple ancestry-informative noncoding variants upstream of SMAD2 with asthma susceptibility. Furthermore, decreased SMAD2 expression in blood was strongly associated with increased asthma risk and increased exacerbations.
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GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes previously identified loci and identifies population-specific signals.
Méndez-Giráldez, R, Gogarten, SM, Below, JE, Yao, J, Seyerle, AA, Highland, HM, Kooperberg, C, Soliman, EZ, Rotter, JI, Kerr, KF, et al
Scientific reports. 2017;(1):17075
Abstract
QT interval prolongation is a heritable risk factor for ventricular arrhythmias and can predispose to sudden death. Most genome-wide association studies (GWAS) of QT were performed in European ancestral populations, leaving other groups uncharacterized. Herein we present the first QT GWAS of Hispanic/Latinos using data on 15,997 participants from four studies. Study-specific summary results of the association between 1000 Genomes Project (1000G) imputed SNPs and electrocardiographically measured QT were combined using fixed-effects meta-analysis. We identified 41 genome-wide significant SNPs that mapped to 13 previously identified QT loci. Conditional analyses distinguished six secondary signals at NOS1AP (n = 2), ATP1B1 (n = 2), SCN5A (n = 1), and KCNQ1 (n = 1). Comparison of linkage disequilibrium patterns between the 13 lead SNPs and six secondary signals with previously reported index SNPs in 1000G super populations suggested that the SCN5A and KCNE1 lead SNPs were potentially novel and population-specific. Finally, of the 42 suggestively associated loci, AJAP1 was suggestively associated with QT in a prior East Asian GWAS; in contrast BVES and CAP2 murine knockouts caused cardiac conduction defects. Our results indicate that whereas the same loci influence QT across populations, population-specific variation exists, motivating future trans-ethnic and ancestrally diverse QT GWAS.
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Genome-wide association study in NSAID-induced acute urticaria/angioedema in Spanish and Han Chinese populations.
Cornejo-García, JA, Liou, LB, Blanca-López, N, Doña, I, Chen, CH, Chou, YC, Chuang, HP, Wu, JY, Chen, YT, Plaza-Serón, Mdel C, et al
Pharmacogenomics. 2013;(15):1857-69
Abstract
AIM: Acute urticaria/angioedema (AUA) induced by cross-intolerance to NSAIDs is the most frequent clinical entity in hypersensitivity reactions to drugs. In this work, we conducted a genome-wide association study in Spanish and Han Chinese patients suffering from NSAID-induced AUA. MATERIALS & METHODS A whole-genome scan was performed on a total of 232 cases (112 Spanish and 120 Han Chinese) with NSAID-induced AUA and 225 unrelated controls (124 Spanish and 101 Han Chinese). RESULTS Although no polymorphism reached genome-wide significance, we obtained suggestive associations for three clusters in the Spanish group (RIMS1, BICC1 and RAD51L 1) and one region in the Han Chinese population (ABI3BP). Five regions showed suggestive associations after meta-analysis: HLF, RAD51L1, COL24A1, GalNAc-T13 and FBXL7. A majority of these genes are related to Ca(2+), cAMP and/or P53 signaling pathways. CONCLUSION The associations described were different from those related to the metabolism of arachidonic acid and could provide new mechanisms underlying NSAID-induced AUA.
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Body mass index and mortality rate among Hispanic adults: a pooled analysis of multiple epidemiologic data sets.
Fontaine, KR, McCubrey, R, Mehta, T, Pajewski, NM, Keith, SW, Bangalore, SS, Crespo, CJ, Allison, DB
International journal of obesity (2005). 2012;(8):1121-6
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Abstract
OBJECTIVE To evaluate the association between body mass index (BMI, kg m⁻²) and mortality rate among Hispanic adults. METHODS AND PROCEDURES Analysis of five data sets (total N=16,798) identified after searching for publicly available, prospective cohort data sets containing relevant information for at least 500 Hispanic respondents (≥18 years at baseline), at least 5 years of mortality follow-up, and measured height and weight. Data sets included the third National Health and Nutrition Examination Survey, the Puerto Rico Heart Health Program (PRHHP), the Hispanic Established Population for Epidemiologic Studies of the Elderly (HEPESE), the San Antonio Heart Study (SAHS) and the Sacramento Area Latino Study on Aging. RESULTS Cox proportional hazards regression models, adjusting for sex and smoking, were fit within three attained-age strata (18 to younger than 60 years, 60 to younger than 70 years, and 70 years and older). We found that underweight was associated with elevated mortality rate for all age groups in the PRHHP (hazard ratios [HRs]=1.38-1.60) and the SAHS (HRs=1.88-2.51). Overweight (HRs=0.38 and 0.84) and obesity grade 2-3 (HRs=0.75 and 0.60) associated with reduced mortality rate in the HEPESE dataset for those in the 60 to younger than 70 years, and 70 years and older attained-age strata. Weighted estimates combining the HRs across the data sets revealed a similar pattern. CONCLUSION Among Hispanic adults, there was no clear evidence that overweight and obesity associate with elevated mortality rate.
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Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.
Elbers, CC, Guo, Y, Tragante, V, van Iperen, EP, Lanktree, MB, Castillo, BA, Chen, F, Yanek, LR, Wojczynski, MK, Li, YR, et al
PloS one. 2012;(12):e50198
Abstract
Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p = 8.8×10(-7) and p = 1.5×10(-6) respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 13.5×10(-12)). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report.