Over 3 billion dollars have been spent on the Human Genome Project, yet few applications of the genetic knowledge from this endeavor are available for clinical practice. Genetic tests currently in early testing hold promise to greatly improve asthma management by allowing clinicians to tailor asthma management to individual needs. At this stage, the field of genetics needs research to help the developers and potential users of these tests to formulate and apply them in ways that maximize their benefits in real-life settings. Ann Chen Wu, MD, MPH, is a pediatrician and health services researcher who is committed to a research career investigating the effects of genetic testing on health outcomes. Via this K08 award, she proposes innovative research and training in an area of emerging importance. She will build on her strong foundation of prior training in health services research by obtaining advanced education and research experience in genetics with an outstanding team of mentors in a rich environment. Dr. Wu's long-term research goals are to create generalizable approaches that enhance the development of genetic tests, and to enable clinicians and policymakers to apply these tests in ways that optimize the health of large populations.
The specific aims of the research plan are to evaluate the effectiveness of recently developed pharmacogenetic tests that predict which patients are at highest risk for not responding to the two most commonly used medications for asthma, beta2-agonists and inhaled corticosteroids. These multi-gene tests have been found efficacious in clinical trials, but have not been tested in general populations where test characteristics may differ. In addition, Dr. Wu proposes to evaluate the projected health benefits, risks, and cost-effectiveness of these pharmacogenetic tests under varying assumptions about test performance and asthma epidemiology. Dr. Wu has unique resources available to her at Hatviard Meidical School, including an accomplished and supportive mentorship team, access to data from two NIH funded clinical trials, and access to a cost- effectiveness model of the natural history of asthma. The research and training proposed here will enable an excellent young investigator to enter an important new field at a critical stage in the field's development.

Public Health Relevance

Few applications of knowledge from the Human Genome have reached clinical practice. This proposal will help assess whether genetic tests that predict poor or good response to asthma medications can be used clinically in real world settings to benefit the health of a general population.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZHL1-CSR-O (M1))
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Tigno, Xenia
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Harvard Pilgrim Health Care, Inc.
United States
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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
Naidoo, D; Wu, A C; Brilliant, M H et al. (2015) A polymorphism in HLA-G modifies statin benefit in asthma. Pharmacogenomics J 15:272-7
Wu, Ann Chen; Gay, Charlene; Rett, Melisa D et al. (2015) Pharmacogenomic test that predicts response to inhaled corticosteroids in adults with asthma likely to be cost-saving. Pharmacogenomics 16:591-600
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 136:1503-1510
Wu, Ann Chen; Himes, Blanca E; Lasky-Su, Jessica et al. (2014) Inhaled corticosteroid treatment modulates ZNF432 gene variant's effect on bronchodilator response in asthmatics. J Allergy Clin Immunol 133:723-8.e3
Tse, Sze Man; Li, Lingling; Butler, Melissa G et al. (2013) Statin exposure is associated with decreased asthma-related emergency department visits and oral corticosteroid use. Am J Respir Crit Care Med 188:1076-82
McGeachie, M J; Wu, A C; Chang, H-H et al. (2013) Predicting inhaled corticosteroid response in asthma with two associated SNPs. Pharmacogenomics J 13:306-11
Wu, Ann Chen; Gregory, Martin; Kymes, Steven et al. (2012) Modeling asthma exacerbations through lung function in children. J Allergy Clin Immunol 130:1065-70
Himes, Blanca E; Jiang, Xiaofeng; Hu, Ruoxi et al. (2012) Genome-wide association analysis in asthma subjects identifies SPATS2L as a novel bronchodilator response gene. PLoS Genet 8:e1002824
Wu, Ann Chen; Tantisira, Kelan; Li, Lingling et al. (2012) Effect of vitamin D and inhaled corticosteroid treatment on lung function in children. Am J Respir Crit Care Med 186:508-13

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