Veterans Caribbean Health Care System

San Juan, Puerto Rico

Veterans Caribbean Health Care System

San Juan, Puerto Rico
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Baran Y.,Tel Aviv University | Pasaniuc B.,Harvard University | Pasaniuc B.,The Broad Institute of MIT and Harvard | Sankararaman S.,The Broad Institute of MIT and Harvard | And 10 more authors.
Bioinformatics | Year: 2012

Motivation: It is becoming increasingly evident that the analysis of genotype data from recently admixed populations is providing important insights into medical genetics and population history. Such analyses have been used to identify novel disease loci, to understand recombination rate variation and to detect recent selection events. The utility of such studies crucially depends on accurate and unbiased estimation of the ancestry at every genomic locus in recently admixed populations. Although various methods have been proposed and shown to be extremely accurate in twoway admixtures (e.g. African Americans), only a few approaches have been proposed and thoroughly benchmarked on multi-way admixtures (e.g. Latino populations of the Americas). Results: To address these challenges we introduce here methods for local ancestry inference which leverage the structure of linkage disequilibrium in the ancestral population (LAMP-LD), and incorporate the constraint of Mendelian segregation when inferring local ancestry in nuclear family trios (LAMP-HAP). Our algorithms uniquely combine hidden Markov models (HMMs) of haplotype diversity within a novel window-based framework to achieve superior accuracy as compared with published methods. Further, unlike previous methods, the structure of our HMM does not depend on the number of reference haplotypes but on a fixed constant, and it is thereby capable of utilizing large datasets while remaining highly efficient and robust to over-fitting. Through simulations and analysis of real data from 489 nuclear trio families from the mainland US, Puerto Rico and Mexico, we demonstrate that our methods achieve superior accuracy compared with published methods for local ancestry inference in Latinos. © The Author 2012. Published by Oxford University Press. All rights reserved.


Pasaniuc B.,University of California at Los Angeles | Sankararaman S.,Harvard University | Torgerson D.G.,University of California at San Francisco | Gignoux C.,University of California at San Francisco | And 13 more authors.
Bioinformatics | Year: 2013

Motivation: Local ancestry analysis of genotype data from recently admixed populations (e.g. Latinos, African Americans) provides key insights into population history and disease genetics. Although methods for local ancestry inference have been extensively validated in simulations (under many unrealistic assumptions), no empirical study of local ancestry accuracy in Latinos exists to date. Hence, interpreting findings that rely on local ancestry in Latinos is challenging.Results: Here, we use 489 nuclear families from the mainland USA, Puerto Rico and Mexico in conjunction with 3204 unrelated Latinos from the Multiethnic Cohort study to provide the first empirical characterization of local ancestry inference accuracy in Latinos. Our approach for identifying errors does not rely on simulations but on the observation that local ancestry in families follows Mendelian inheritance. We measure the rate of local ancestry assignments that lead to Mendelian inconsistencies in local ancestry in trios (MILANC), which provides a lower bound on errors in the local ancestry estimates. We show that MILANC rates observed in simulations underestimate the rate observed in real data, and that MILANC varies substantially across the genome. Second, across a wide range of methods, we observe that loci with large deviations in local ancestry also show enrichment in MILANC rates. Therefore, local ancestry estimates at such loci should be interpreted with caution. Finally, we reconstruct ancestral haplotype panels to be used as reference panels in local ancestry inference and show that ancestry inference is significantly improved by incoroprating these reference panels. © 2013 The Author. Published by Oxford University Press. All rights reserved.


Nishimura K.K.,University of California at San Francisco | Galanter J.M.,University of California at San Francisco | Roth L.A.,University of California at San Francisco | Oh S.S.,University of California at San Francisco | And 19 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2013

Rationale: Air pollution is a known asthma trigger and has been associatedwith short-termasthmasymptoms,airway inflammation,decreased lung function, and reduced response to asthma rescuemedications. Objectives: To assess a causal relationship between air pollution and childhood asthma using data that address temporality by estimating air pollution exposures before the development of asthma and to establish the generalizability of the association by studying diverse racial/ethnic populations in different geographic regions. Methods: This study included Latino (n = 3,343) and African American (n=977) participants with and without asthma from five urban regions in the mainland United States and Puerto Rico. Residential history and data from local ambient airmonitoring stationswere used to estimate average annual exposure to five air pollutants: ozone, nitrogen dioxide (NO2), sulfur dioxide, particulatematter not greater than 10 mm in diameter, and particulatematter not greater than 2.5 mmindiameter. Within each region, we performed logistic regression to determine the relationship between early-life exposure to air pollutants and subsequent asthmadiagnosis.Arandom-effectsmodelwasusedtocombinetheregionspecific effects and generate summary odds ratios for each pollutant. Measurements and Main Results: After adjustment for confounders, a 5-ppb increase in average NO2 during the first year of life was associatedwith anodds ratio of 1.17 for physician-diagnosedasthma (95% confidence interval, 1.04-1.31). Conclusions: Early-life NO2 exposure is associated with childhood asthma in Latinos and African Americans. These results add to a growing body of evidence that traffic-related pollutants may be causally related to childhood asthma. © 2013 by the American Thoracic Society.


Borrell L.N.,City University of New York | Oh S.S.,Center for Tobacco Control Research and Education | Tcheurekdjian H.,Case Western Reserve University | Tcheurekdjian H.,Allergy Immunology Associates Inc. | And 10 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2013

Rationale: Obesity is associated with increased asthma morbidity, lower drug responsiveness to inhaled corticosteroids, and worse asthma control. However, most prior investigations on obesity and asthma control have not focused on pediatric populations, considered environmental exposures, or included minority children. Objectives: To examine the association between body mass index categories and asthma control among boys and girls; and whether these associations are modified by age and race/ethnicity. Methods: Children and adolescents ages 8-19 years (n = 2,174) with asthma were recruited from the Genes-environments and Admixture in Latino Americans (GALA II) Study and the Study of African Americans, Asthma, Genes, and Environments (SAGE II). Ordinal logistic regression was used to estimate odds ratios (OR) and their confidence intervals (95% CI) for worse asthma control. Measurements and Main Results: In adjusted analyses, boys who were obese had a 33% greater chance of having worse asthma control than their normal-weight counterparts (OR, 1.33; 95% CI, 1.04-1.71). However, for girls this association variedwith race andethnicity (P interaction = 0.008). When compared with their normal-weight counterparts, obese African American girls (OR, 0.65; 95% CI, 0.41- 1.05) were more likely to have better controlled asthma, whereas Mexican American girls had a 1.91 (95% CI, 1.12-3.28) greater odds of worse asthma control. Conclusions: Worse asthma control is uniformly associated with increased body mass index in boys. Among girls, the direction of this association varied with race/ethnicity. Copyright © 2013 by the American Thoracic Society.


Thakur N.,University of California at San Francisco | Oh S.S.,University of California at San Francisco | Nguyen E.A.,University of California at San Francisco | Martin M.,University of California at San Francisco | And 21 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2013

Rationale: The burden of asthma is highest among socioeconomically disadvantagedpopulations; however, its impact is differentially distributed among racial and ethnic groups. Objectives: To assess the collective effect of maternal educational attainment, annual household income, and insurance type on childhood asthma among minority, urban youth. Methods: We included Mexican American (n = 485), other Latino (n = 217), and African American (n = 1,141) children (aged 8-21 yr) with and without asthma from the San Francisco Bay Area. An index was derived from maternal educational attainment, annual household income, and insurance type to assess the collective effect of socioeconomic status on predicting asthma. Logistic regression stratified by racial and ethnic group was used to estimate adjusted odds ratios (aOR) and their 95% confidence intervals (CI). We further examined whether acculturation explained the socioeconomicasthma association in our Latino population. Measurements and Main Results: In the adjusted analyses, African American children had 23% greater odds of asthma with each decrease in the socioeconomic index (aOR, 1.23; 95% CI, 1.09-1.38). Conversely, Mexican American children have 17% reduced odds of asthma with each decrease in the socioeconomic index (aOR, 0.83; 95% CI, 0.72-0.96) and this relationship was not fully explained by acculturation. This association was not observed in the other Latino group. Conclusions: Socioeconomic status plays an important role in predicting asthma, but has different effects depending on race and ethnicity. Further steps are necessary to better understand the risk factors through which socioeconomic status could operate in these populations to prevent asthma. Copyright © 2013 by the American Thoracic Society.


PubMed | Ford Motor Company, Childrens Hospital Oakland Research Institute, Stanford University, Bay Area Pediatrics and 20 more.
Type: Journal Article | Journal: The Journal of allergy and clinical immunology | Year: 2015

IgE is a key mediator of allergic inflammation, and its levels are frequently increased in patients with allergic disorders.We sought to identify genetic variants associated with IgE levels in Latinos.We performed a genome-wide association study and admixture mapping of total IgE levels in 3334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1564 European Americans, and 3187 African Americans from independent studies.We confirmed associations of 6 genes identified by means of previous genome-wide association studies and identified a novel genome-wide significant association of a polymorphism in the zinc finger protein 365 gene (ZNF365) with total IgE levels (rs200076616, P= 2.3 10(-8)). We next identified 4 admixture mapping peaks (6p21.32-p22.1, 13p22-31, 14q23.2, and 22q13.1) at which local African, European, and/or Native American ancestry was significantly associated with IgE levels. The most significant peak was 6p21.32-p22.1, where Native American ancestry was associated with lower IgE levels (P= 4.95 10(-8)). All but 22q13.1 were replicated in an independent sample of Latinos, and 2 of the peaks were replicated in African Americans (6p21.32-p22.1 and 14q23.2). Fine mapping of 6p21.32-p22.1 identified 6 genome-wide significant single nucleotide polymorphisms in Latinos, 2 of which replicated in European Americans. Another single nucleotide polymorphism was peak-wide significant within 14q23.2 in African Americans (rs1741099, P= 3.7 10(-6)) and replicated in non-African American samples (P= .011).We confirmed genetic associations at 6 genes and identified novel associations within ZNF365, HLA-DQA1, and 14q23.2. Our results highlight the importance of studying diverse multiethnic populations to uncover novel loci associatedwith total IgE levels.


PubMed | Northwestern University, Ford Motor Company, Baylor College of Medicine, City University of New York and 5 more.
Type: Journal Article | Journal: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology | Year: 2016

Pest allergen sensitization is associated with asthma morbidity in urban youth but minimally explored in Latino populations. Specifically, the effect of mouse sensitization on the risk of asthma exacerbation has been unexplored in Latino subgroups.To evaluate whether pest allergen sensitization is a predictor of asthma exacerbations and poor asthma control in urban minority children with asthma.Latino and African American children (8-21 years old) with asthma were recruited from 4 sites across the United States. Logistic regression models evaluated the association of mouse or cockroach sensitization with asthma-related acute care visits or hospitalizations.A total of 1,992 children with asthma in the Genes-environments and Admixture in Latino American (GALA-II) and Study of African-Americans, Asthma, Genes, and Environments (SAGE-II) cohorts were studied. Asthmatic children from New York had the highest rate of pest allergen sensitization (42% mouse, 56% cockroach), with the lowest rate in San Francisco (4% mouse, 8% cockroach). Mouse sensitization, more than cockroach, was associated with increased odds of acute care visits (adjusted odds ratio [aOR], 1.47; 95% CI, 1.07-2.03) or hospitalizations (aOR, 3.07; 95% CI, 1.81-5.18), even after controlling for self-reported race and site of recruitment. In stratified analyses, Mexican youth sensitized to mouse allergen did not have higher odds of asthma exacerbation. Other Latino and Puerto Rican youth sensitized to mouse had higher odds of hospitalization for asthma (aORs, 4.57 [95% CI, 1.86-11.22] and 10.01 [95% CI, 1.77-56.6], respectively) but not emergency department visits.Pest allergen sensitization is associated with a higher odds of asthma exacerbations in urban minority youth. Puerto Rican and Other Latino youth sensitized to mouse were more likely to have asthma-related hospitalizations than Mexican youth.


Moreno-Estrada A.,Stanford University | Gignoux C.R.,Stanford University | Gignoux C.R.,University of California at San Francisco | Fernandez-Lopez J.C.,Instituto Nacional Of Medicina Genomica Inmegen | And 45 more authors.
Science | Year: 2014

Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide.


PubMed | Northwestern University, Baylor College of Medicine, Lehman College, CUNY, Ford Motor Company and 7 more.
Type: Journal Article | Journal: PloS one | Year: 2016

Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk.We included Latino children, adolescents, and young adults aged 8-21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function.RSV infection (OR 9.9, 95%CI 4.9-20.2) and other LRI (OR 9.1, 95%CI 7.2-11.5) were independently associated with asthma, but PAI-1 genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3-50.2) and genotype-LRI (OR 11.7, 95% CI 8.8-16.4). A joint effect of genotype-RSV resulted in a 3.1-fold increased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted and FEV1/FVC % predicted were further reduced in the genotype-LRI group ( -2.1, 95% CI -4.0 to -0.2; -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group ( -3.1, 95% CI -6.1 to -0.2) with a trend for lower FEV1/FVC % predicted.A genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population.


PubMed | Northwestern University, Baylor College of Medicine, Lehman College, CUNY, Ford Motor Company and 5 more.
Type: Journal Article | Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology | Year: 2016

Younger maternal age at birth is associated with increased risk of asthma in offspring in European descent populations, but has not been studied in Latino populations.We sought to examine the relationship between maternal age at birth and prevalence of asthma in a nationwide study of Latino children.We included 3473 Latino children aged 8-21 years (1696 subjects with physician-diagnosed asthma and 1777 healthy controls) from five US centres and Puerto Rico recruited from July 2008 through November 2011. We used multiple logistic regression models to examine the effect of maternal age at birth on asthma in offspring overall and in analyses stratified by ethnic subgroup (Mexican American, Puerto Rican and other Latino). Secondary analyses evaluated the effects of siblings, acculturation and income on this relationship.Maternal age < 20 years was significantly associated with decreased odds of asthma in offspring, independent of other risk factors (OR = 0.73, 95% CI: 0.57-0.93). In subgroup analyses, the protective effect of younger maternal age was observed only in Mexican Americans (OR = 0.53, 95% CI: 0.36, 0.79). In Puerto Ricans, older maternal age was associated with decreased odds of asthma (OR = 0.65, 95% CI: 0.44-0.97). In further stratified models, the protective effect of younger maternal age in Mexican Americans was seen only in children without older siblings (OR = 0.44, 95% CI: 0.23-0.81).In contrast to European descent populations, younger maternal age was associated with decreased odds of asthma in offspring in Mexican American women. Asthma is common in urban minority populations but the factors underlying the varying prevalence among different Latino ethnicities in the United States is not well understood. Maternal age represents one factor that may help to explain this variability.

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