Abstract
Background The primary rescue medication to treat acute asthma exacerbation is the short-acting β2-adrenergic receptor agonist; however, there is variation in how well a patient responds to treatment. Although these differences might be due to environmental factors, there is mounting evidence for a genetic contribution to variability in bronchodilator response (BDR). Objective To identify genetic variation associated with bronchodilator drug response in Latino children with asthma. Methods We performed a genome-wide association study (GWAS) for BDR in 1782 Latino children with asthma using standard linear regression, adjusting for genetic ancestry and ethnicity, and performed replication studies in an additional 531 Latinos. We also performed admixture mapping across the genome by testing for an association between local European, African, and Native American ancestry and BDR, adjusting for genomic ancestry and ethnicity. Results We identified 7 genetic variants associated with BDR at a genome-wide significant threshold (P <5 × 10-8), all of which had frequencies of less than 5%. Furthermore, we observed an excess of small P values driven by rare variants (frequency,
| Original language | English (US) |
|---|---|
| Journal | The Journal of Allergy and Clinical Immunology |
| Volume | 133 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2014 |
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Keywords
- admixture mapping
- asthma
- Bronchodilator response
- genome-wide association study
- Latinos
- rare variants
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
A genome-wide association study of bronchodilator response in Latinos implicates rare variants. / Drake, Katherine A.; Torgerson, Dara G.; Gignoux, Christopher R.; Galanter, Joshua M.; Roth, Lindsey A.; Huntsman, Scott; Eng, Celeste; Oh, Sam S.; Yee, Sook Wah; Lin, Lawrence; Bustamante, Carlos D.; Moreno-Estrada, Andrés; Sandoval, Karla; Davis, Adam; Borrell, Luisa N.; Farber, Harold J.; Kumar, Rajesh; Avila, Pedro C.; Brigino-Buenaventura, Emerita; Chapela, Rocio; Ford, Jean G.; Lenoir, Michael A.; Lurmann, Fred; Meade, Kelley; Serebrisky, Denise; Thyne, Shannon; Rodríguez-Cintrón, William; Sen, Saunak; Rodríguez-Santana, José R.; Hernandez, Ryan D.; Giacomini, Kathleen M.; Burchard, Esteban G.
In: The Journal of Allergy and Clinical Immunology, Vol. 133, No. 2, 02.2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A genome-wide association study of bronchodilator response in Latinos implicates rare variants
AU - Drake, Katherine A.
AU - Torgerson, Dara G.
AU - Gignoux, Christopher R.
AU - Galanter, Joshua M.
AU - Roth, Lindsey A.
AU - Huntsman, Scott
AU - Eng, Celeste
AU - Oh, Sam S.
AU - Yee, Sook Wah
AU - Lin, Lawrence
AU - Bustamante, Carlos D.
AU - Moreno-Estrada, Andrés
AU - Sandoval, Karla
AU - Davis, Adam
AU - Borrell, Luisa N.
AU - Farber, Harold J.
AU - Kumar, Rajesh
AU - Avila, Pedro C.
AU - Brigino-Buenaventura, Emerita
AU - Chapela, Rocio
AU - Ford, Jean G.
AU - Lenoir, Michael A.
AU - Lurmann, Fred
AU - Meade, Kelley
AU - Serebrisky, Denise
AU - Thyne, Shannon
AU - Rodríguez-Cintrón, William
AU - Sen, Saunak
AU - Rodríguez-Santana, José R.
AU - Hernandez, Ryan D.
AU - Giacomini, Kathleen M.
AU - Burchard, Esteban G.
PY - 2014/2
Y1 - 2014/2
N2 - Background The primary rescue medication to treat acute asthma exacerbation is the short-acting β2-adrenergic receptor agonist; however, there is variation in how well a patient responds to treatment. Although these differences might be due to environmental factors, there is mounting evidence for a genetic contribution to variability in bronchodilator response (BDR). Objective To identify genetic variation associated with bronchodilator drug response in Latino children with asthma. Methods We performed a genome-wide association study (GWAS) for BDR in 1782 Latino children with asthma using standard linear regression, adjusting for genetic ancestry and ethnicity, and performed replication studies in an additional 531 Latinos. We also performed admixture mapping across the genome by testing for an association between local European, African, and Native American ancestry and BDR, adjusting for genomic ancestry and ethnicity. Results We identified 7 genetic variants associated with BDR at a genome-wide significant threshold (P <5 × 10-8), all of which had frequencies of less than 5%. Furthermore, we observed an excess of small P values driven by rare variants (frequency,
AB - Background The primary rescue medication to treat acute asthma exacerbation is the short-acting β2-adrenergic receptor agonist; however, there is variation in how well a patient responds to treatment. Although these differences might be due to environmental factors, there is mounting evidence for a genetic contribution to variability in bronchodilator response (BDR). Objective To identify genetic variation associated with bronchodilator drug response in Latino children with asthma. Methods We performed a genome-wide association study (GWAS) for BDR in 1782 Latino children with asthma using standard linear regression, adjusting for genetic ancestry and ethnicity, and performed replication studies in an additional 531 Latinos. We also performed admixture mapping across the genome by testing for an association between local European, African, and Native American ancestry and BDR, adjusting for genomic ancestry and ethnicity. Results We identified 7 genetic variants associated with BDR at a genome-wide significant threshold (P <5 × 10-8), all of which had frequencies of less than 5%. Furthermore, we observed an excess of small P values driven by rare variants (frequency,
KW - admixture mapping
KW - asthma
KW - Bronchodilator response
KW - genome-wide association study
KW - Latinos
KW - rare variants
UR - http://www.scopus.com/inward/record.url?scp=84895059577&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84895059577&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2013.06.043
DO - 10.1016/j.jaci.2013.06.043
M3 - Article
C2 - 23992748
AN - SCOPUS:84895059577
VL - 133
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 2
ER -