Asthma is a respiratory disease characterized by variable airways obstruction, airways inflammation and bronchial hyperresponsiveness (BHR). There are increases in asthma mortality and prevalence in the US, especially in African- Americans. Multiple studies suggest that both genetic and environmental factors are important in asthma susceptibility.
The aim of the Collaborative Study of the Genetics of Asthma (CSGA) is to identify asthma susceptibility loci. The CSGA is composed of four centers (Johns Hopkins University, University of Chicago, University of Maryland, University of Minnesota, and a data coordinating center at Bowman Gray). At each center, families were ascertained through two siblings with asthma. All family members were characterized with spirometry, bronchial responsiveness to methacholine or reversibility testing, skin-tests and questionnaire data. The initial genome screen has been completed on the first 237 sib pairs from three racial groups (African-American, Caucasian and Hispanic), and genotyping On the remaining family members and families will be completed before the start of the renewal proposal. Therefore, the initial aim of the CSGA to map susceptibility regions has been completed, with detection of several novel chromosomal regions, and replication of several regions previously linked to associated phenotypes. In order to determine the importance of these regions in asthma susceptibility and the impact of environmental rink factors, we propose to l) evaluate the evidence for linkage in the complete CSGA data using 2-point, multipoint and multilocus approaches for asthma and associated phenotypes (including BHR, total serum IgE and skin test reactivity to standardized allergens); 2) perform fine mapping studies of regions using additional genetic markers to obtain a < 2 cM map; 3) identify candidate genes and novel sequence variants; and 4) characterize a patient population with asthma to study identified variants with respect to asthma severity and bronchial inflammation. These studies will allow us to identify asthma susceptibility genes and their variants, interactions with other genes and environmental risk factors, as well as provide insight for the development of improved treatment and ultimate prevention of asthma.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL049612-08
Application #
6056255
Study Section
Special Emphasis Panel (ZHL1-CSR-G (M3))
Project Start
1992-09-30
Project End
2002-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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
Myers, Rachel A; Himes, Blanca E; Gignoux, Christopher R et al. (2012) Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans. J Allergy Clin Immunol 130:1294-301
Torgerson, Dara G; Capurso, Daniel; Mathias, Rasika A et al. (2012) Resequencing candidate genes implicates rare variants in asthma susceptibility. Am J Hum Genet 90:273-81
Wegmann, Daniel; Kessner, Darren E; Veeramah, Krishna R et al. (2011) Recombination rates in admixed individuals identified by ancestry-based inference. Nat Genet 43:847-53
Mathias, Rasika A; Grant, Audrey V; Rafaels, Nicholas et al. (2010) A genome-wide association study on African-ancestry populations for asthma. J Allergy Clin Immunol 125:336-346.e4
Gao, Pei-Song; Shimizu, Kenichi; Grant, Audrey V et al. (2010) Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma. Eur J Hum Genet 18:713-9
Blumenthal, Malcolm N; Langefeld, Carl D; Barnes, Kathleen C et al. (2006) A genome-wide search for quantitative trait loci contributing to variation in seasonal pollen reactivity. J Allergy Clin Immunol 117:79-85
Gao, Pei-Song; Mathias, Rasika A; Plunkett, Beverly et al. (2005) Genetic variants of the T-cell immunoglobulin mucin 1 but not the T-cell immunoglobulin mucin 3 gene are associated with asthma in an African American population. J Allergy Clin Immunol 115:982-8
Blumenthal, M N; Ober, C; Beaty, T H et al. (2004) Genome scan for loci linked to mite sensitivity: the Collaborative Study on the Genetics of Asthma (CSGA). Genes Immun 5:226-31
Blumenthal, Malcolm N; Langefeld, Carl D; Beaty, Terri H et al. (2004) A genome-wide search for allergic response (atopy) genes in three ethnic groups: Collaborative Study on the Genetics of Asthma. Hum Genet 114:157-64

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