Asthma affects over 300 million individuals worldwide. Asthma symptoms are tightly correlated with overall quality of life;persistent symptoms resulting in poor asthma control leads to disproportionate morbidity and cost. Genome-wide association studies have been extensively applied to the study of asthma susceptibility and lung function in asthma, but have yet to be applied in a systematic fashion to studies of self-reported symptoms in asthma. The major goal of this project is to thoroughly investigate the genetic origins of asthma symptoms via genome-wide association study. To accomplish this, we have specified three related but independent aims.
The first aim evaluates data from over 500,000 genetic markers for their association with symptoms as reported at the time of enrollment into a clinical trial or clinical cohort. The markers with the strongest evidence for association will be tested for replication in independent clinical cohorts.
The second aim seeks to understand the genetic basis for response of symptoms to drug treatment (pharmacogenetics). Instead of analyzing baseline symptoms, the change in symptoms as a response to inhaled corticosteroid medications will be the primary outcome phenotype for this aim, which will also use genome-wide association testing and replication methods.
Our final aim will be to develop a model, using both genotype and phenotypic characteristics, including demographic, psychosocial, and behavioral factors, to predict who is at greatest risk of developing persistent symptoms in asthma. Dozens to hundreds of genetic markers will be used to develop these predictive tests, which will be formulated and validated for both persistent symptoms and treatment response of symptoms. We believe that these findings will uncover the genetic basis for symptoms in asthma and lead to novel interventions to predict and alleviate this major health care problem.

Public Health Relevance

Asthma affects an estimated 300 million individuals worldwide and accounts for approximately $20 billion in direct health care costs in the United States annually, with a disproportionate proportion of those costs allocated to uncontrolled, persistently symptomatic individuals. The identification of genetic variants that can be used as the basis of a prognostic test to predict which individuals will or will not demonstrate symptoms and respond to therapy has the potential to substantially decrease both morbidity and financial burden related to asthma as well as to improve the overall quality of life for subjects with asthma and their care providers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Research Project (R01)
Project #
5R01NR013391-03
Application #
8517208
Study Section
Special Emphasis Panel (ZNR1-REV-M (09))
Program Officer
Tully, Lois
Project Start
2011-09-27
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$423,045
Indirect Cost
$186,045
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Kho, Alvin T; Sharma, Sunita; Davis, Joshua S et al. (2016) Circulating MicroRNAs: Association with Lung Function in Asthma. PLoS One 11:e0157998
Dahlin, A; Litonjua, A; Irvin, C G et al. (2016) Genome-wide association study of leukotriene modifier response in asthma. Pharmacogenomics J 16:151-7
Park, H-W; Tse, S; Yang, W et al. (2016) A genetic factor associated with low final bone mineral density in children after a long-term glucocorticoids treatment. Pharmacogenomics J :
McGeachie, Michael J; Yates, Katherine P; Zhou, Xiaobo et al. (2016) Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma. N Engl J Med 374:1842-52
Davis, Joshua S; Weiss, Scott T; Tantisira, Kelan G (2015) Asthma Pharmacogenomics: 2015 Update. Curr Allergy Asthma Rep 15:42
Clemmer, George L; Wu, Ann Chen; Rosner, Bernard et al. (2015) Measuring the corticosteroid responsiveness endophenotype in asthmatic patients. J Allergy Clin Immunol 136:274-81.e8
McGeachie, Michael J; Wu, Ann C; Tse, Sze Man et al. (2015) CTNNA3 and SEMA3D: Promising loci for asthma exacerbation identified through multiple genome-wide association studies. J Allergy Clin Immunol 136:1503-10
Park, Heung-Woo; Ge, Bing; Tse, Szeman et al. (2015) Genetic risk factors for decreased bone mineral accretion in children with asthma receiving multiple oral corticosteroid bursts. J Allergy Clin Immunol 136:1240-6.e1-8
Strunk, Robert C; Colvin, Ryan; Bacharier, Leonard B et al. (2015) Airway Obstruction Worsens in Young Adults with Asthma Who Become Obese. J Allergy Clin Immunol Pract 3:765-71.e2
Vijverberg, S J H; Koster, E S; Tavendale, R et al. (2015) ST13 polymorphisms and their effect on exacerbations in steroid-treated asthmatic children and young adults. Clin Exp Allergy 45:1051-9

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