In the United States, asthma prevalence is highest in Puerto Ricans (26%) and lowest in Mexicans (10%). This is paradoxical since both groups are considered """"""""Hispanic"""""""" or """"""""Latino"""""""". Although there are many potential explanations for this observation, including environmental and socioeconomic factors, one potential explanation is that the genetic predisposition to asthma differs among subgroups within the Latino population. Latinos are admixed and share varying proportions of African, Native American and European ancestry. The mixed ancestry of Latinos provides unique opportunities in epidemiological and genetic studies and may be useful in untangling complex gene-gene and gene-environment interactions in disease susceptibility. This proposal will take advantage of clinical data and genomic DNA on 2,100 Puerto Rican and 1,500 Mexican asthma cases and controls collected as part of two large studies of asthma in Latinos (GALA 1 and GALA 2). The goal of this proposal is to perform genome-wide association analyses to identify genetic factors associated with asthma and related phenotypes in Puerto Ricans and Mexicans. In addition, potential interactions between these genetic factors and other genes and environmental variables will be investigated. Specifically, we will: 1) genotype Puerto Rican and Mexican asthma cases and controls using the Affymetrix state-of-art 500K GeneChip arrays, 2) perform genome-wide association analysis on 500K GeneChip data to identify SNPs associated with asthma, asthma severity and bronchodilator response. The analysis will include clinical and demographic characteristics, environmental factors and individual admixture estimates to correct for potential confounders. In addition, admixture mapping analysis will be performed to complement the genome-wide association analysis. Admixture mapping may identify novel regions that harbor racial/ethnic specific alleles for asthma and related phenotypes;and 3) fine map SNPs significantly associated with asthma and related phenotypes in genome-wide analyses (initial-hit SNPs). To our knowledge this is the first proposal to perform a genome-wide association analysis for asthma and related phenotypes in Latinos. Due to the size and scope of this project, the results of this study should substantially increase our understanding of the etiology of asthma and drug response. By gaining a better understanding of asthma risk factors in diverse populations, this proposal is consistent with the goals established by Healthy People 2010, which are to eliminate health disparities among different segments of the population.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL088133-05
Application #
8230694
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Banks-Schlegel, Susan P
Project Start
2008-03-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2014-02-28
Support Year
5
Fiscal Year
2012
Total Cost
$725,733
Indirect Cost
$256,003
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Gour, Naina; Lajoie, Stephane; Smole, Ursula et al. (2018) Dysregulated invertebrate tropomyosin-dectin-1 interaction confers susceptibility to allergic diseases. Sci Immunol 3:
Park, Danny S; Eskin, Itamar; Kang, Eun Yong et al. (2018) An ancestry-based approach for detecting interactions. Genet Epidemiol 42:49-63
Oh, Sam S; Du, Randal; Zeiger, Andrew M et al. (2017) Breastfeeding associated with higher lung function in African American youths with asthma. J Asthma 54:856-865
Sherenian, M G; Cho, S H; Levin, A et al. (2017) PAI-1 gain-of-function genotype, factors increasing PAI-1 levels, and airway obstruction: The GALA II Cohort. Clin Exp Allergy 47:1150-1158
Yan, Qi; Brehm, John; Pino-Yanes, Maria et al. (2017) A meta-analysis of genome-wide association studies of asthma in Puerto Ricans. Eur Respir J 49:
Johnston, Henry Richard; Hu, Yi-Juan; Gao, Jingjing et al. (2017) Identifying tagging SNPs for African specific genetic variation from the African Diaspora Genome. Sci Rep 7:46398
Thakur, Neeta; Barcelo, Nicolas E; Borrell, Luisa N et al. (2017) Perceived Discrimination Associated With Asthma and Related Outcomes in Minority Youth: The GALA II and SAGE II Studies. Chest 151:804-812
Abid, Z; Oh, S S; Hu, D et al. (2016) Maternal age and asthma in Latino populations. Clin Exp Allergy 46:1398-1406
Kessler, Michael D; Yerges-Armstrong, Laura; Taub, Margaret A et al. (2016) Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry. Nat Commun 7:12521
Rahmani, Elior; Zaitlen, Noah; Baran, Yael et al. (2016) Sparse PCA corrects for cell type heterogeneity in epigenome-wide association studies. Nat Methods 13:443-5

Showing the most recent 10 out of 86 publications