4 R37 HL066289-10 - MERIT Extension Principal Investigator/Program Director (Last, First, Middle): WEISS, Scott T. PROJECT SUIVIMARY (See instructions): Asthma remains a major public health problem in the United States and worldwide affecting 300 million people in the US with health care costs of >20 billion dollars/year. Asthma Is a complex disease, likely influenced by genetic and environmental factors. Asthma genetic epidemiology has made significant progress identifying over 43 genes via candidate gene studies, 6 genes via linkage and fine mapping and 3 genes via genome-wide association studies (GWAS). Although asthma is a significant cause of morbidity among certain Hispanic groups in the US (e.g., Puerto Ricans) and Hispanic America (e.g., Costa Ricans), relatively few genetic studies have included Hispanic individuals. Most - but not all - Hispanics have variable proportions of European, Amerindian, and African ancestry, and there is marked variation in asthma prevalence and severity within Hispanic sub-populations, making genetic studies of asthma in Hispanics particularly challenging. To reduce this heterogeneity, we have been studying the genetics of asthma in a relatively homogeneous Hispanic population with high prevalence of asthma (~24% in adolescents) in the Central Valley of Costa Rica for the past 8 years. For this renewal, we have combined our Costa Rican population with the CAMP trios to attempt to identify all the genes for childhood asthma. We will continue to contribute to advancing our understanding of asthma genetics by using novel methods to find replicated asthma genes. In addition, multiple sets of studies are available for this grant application to provide the unique opportunity to identify genetic determinants of asthma that are specific to Hispanic populations, while, at the same time, universal genetic determinants that are relevant for Hispanic populations and Caucasian populations will be discovered. To identify these variants we will perform three different joint-analysis of the available GWAS: a joint analysis of Costa Rica and CAMP will be performed, followed by an in silico meta analysis of Costa Rica and Mexican trios from the EVE consortium and, finally, an overall analysis of Costa Rica, CAMP, and EVE. We believe that by conducting our proposed genome-wide association study, we will have the most powerful and comprehensive approach to identification of asthma-susceptibility genes, and our bioinformatics tools will allow us to take full advantage of information deriving from our experiments to create a bioinformatically-integrated program in ainway disease genetics.

Public Health Relevance

To date, there has been only one genome-wide association study of asthma and/or its intermediate phenotypes in a Hispanic (Mexican) population. Our study addresses an insufficiently studied problem: the genetics of asthma in Hispanic subgroups disproportionately affected by asthma: Hispanics in general and Costa Ricans in particular. This proposal should lead to the identification of asthma-susceptibility genes in general, and among Hispanics in particular.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HL066289-13
Application #
8644843
Study Section
Special Emphasis Panel (NSS)
Program Officer
Banks-Schlegel, Susan P
Project Start
2001-07-10
Project End
2016-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
13
Fiscal Year
2014
Total Cost
$1,486,329
Indirect Cost
$653,651
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Myers, Rachel A; Scott, Nicole M; Gauderman, W James et al. (2014) Genome-wide interaction studies reveal sex-specific asthma risk alleles. Hum Mol Genet 23:5251-9
Zhou, XueZhong; Menche, Jörg; Barabási, Albert-László et al. (2014) Human symptoms-disease network. Nat Commun 5:4212
Jackson, Daniel J; Hartert, Tina V; Martinez, Fernando D et al. (2014) Asthma: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases. Ann Am Thorac Soc 11 Suppl 3:S139-45
Duan, Q L; Lasky-Su, J; Himes, B E et al. (2014) A genome-wide association study of bronchodilator response in asthmatics. Pharmacogenomics J 14:41-7
Sharma, Sunita; Zhou, Xiaobo; Thibault, Derek M et al. (2014) A genome-wide survey of CD4(+) lymphocyte regulatory genetic variants identifies novel asthma genes. J Allergy Clin Immunol 134:1153-62
Bunyavanich, Supinda; Schadt, Eric E; Himes, Blanca E et al. (2014) Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis. BMC Med Genomics 7:48
Levin, Albert M; Mathias, Rasika A; Huang, Lili et al. (2013) A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations. J Allergy Clin Immunol 131:1176-84
Lange, Nancy E; Zhou, Xiaobo; Lasky-Su, Jessica et al. (2011) Comprehensive genetic assessment of a functional TLR9 promoter polymorphism: no replicable association with asthma or asthma-related phenotypes. BMC Med Genet 12:26
Himes, Blanca E; Klanderman, Barbara; Ziniti, John et al. (2011) Association of SERPINE2 with asthma. Chest 140:667-74
Torgerson, Dara G; Ampleford, Elizabeth J; Chiu, Grace Y et al. (2011) Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat Genet 43:887-92

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