Development of a Pharmacogenetic Predictive Test in asthma: proof of concept. Wu, A. C., Himes, B. E., Lasky-Su, J., Litonjua, A., Li, L., Lange, C., Lima, J., Irvin, C. G., & Weiss, S. T. Pharmacogenet Genomics, 20(2):86-93, 2009. ![Development of a Pharmacogenetic Predictive Test in asthma: proof of concept [link]](https://bibbase.org/img/filetypes/link.svg "link")
_mendeley Paper doi abstract bibtex OBJECTIVE: To assess the feasibility of developing a Combined Clinical and Pharmacogenetic Predictive Test, comprised of multiple single nucleotide polymorphisms (SNPs) that is associated with poor bronchodilator response (BDR). METHODS: We genotyped SNPs that tagged the whole genome of the parents and children in the Childhood Asthma Management Program (CAMP) and implemented an algorithm using a family-based association test that ranked SNPs by statistical power. The top eight SNPs that were associated with BDR comprised the Pharmacogenetic Predictive Test. The Clinical Predictive Test was comprised of baseline forced expiratory volume in 1 s (FEV1). We evaluated these predictive tests and a Combined Clinical and Pharmacogenetic Predictive Test in three distinct populations: the children of the CAMP trial and two additional clinical trial populations of asthma. Our outcome measure was poor BDR, defined as BDR of less than 20th percentile in each population. BDR was calculated as the percent difference between the prebronchodilator and postbronchodilator (two puffs of albuterol at 180 microg/puff) FEV1 value. To assess the predictive ability of the test, the corresponding area under the receiver operating characteristic curves (AUROCs) were calculated for each population. RESULTS: The AUROC values for the Clinical Predictive Test alone were not significantly different from 0.50, the AUROC of a random classifier. Our Combined Clinical and Pharmacogenetic Predictive Test comprised of genetic polymorphisms in addition to FEV1 predicted poor BDR with an AUROC of 0.65 in the CAMP children (n = 422) and 0.60 (n = 475) and 0.63 (n = 235) in the two independent populations. Both the Combined Clinical and Pharmacogenetic Predictive Test and the Pharmacogenetic Predictive Test were significantly more accurate than the Clinical Predictive Test (AUROC between 0.44 and 0.55) in each of the populations. CONCLUSION: Our finding that genetic polymorphisms with a clinical trait are associated with BDR suggests that there is promise in using multiple genetic polymorphisms simultaneously to predict which asthmatics are likely to respond poorly to bronchodilators.
@article{ mendeley_5296665511,
isauthor = {1},
isbn = {1744-6880 (Electronic)
1744-6872 (Linking)},
abstract = {OBJECTIVE: To assess the feasibility of developing a Combined Clinical and Pharmacogenetic Predictive Test, comprised of multiple single nucleotide polymorphisms (SNPs) that is associated with poor bronchodilator response (BDR). METHODS: We genotyped SNPs that tagged the whole genome of the parents and children in the Childhood Asthma Management Program (CAMP) and implemented an algorithm using a family-based association test that ranked SNPs by statistical power. The top eight SNPs that were associated with BDR comprised the Pharmacogenetic Predictive Test. The Clinical Predictive Test was comprised of baseline forced expiratory volume in 1 s (FEV1). We evaluated these predictive tests and a Combined Clinical and Pharmacogenetic Predictive Test in three distinct populations: the children of the CAMP trial and two additional clinical trial populations of asthma. Our outcome measure was poor BDR, defined as BDR of less than 20th percentile in each population. BDR was calculated as the percent difference between the prebronchodilator and postbronchodilator (two puffs of albuterol at 180 microg/puff) FEV1 value. To assess the predictive ability of the test, the corresponding area under the receiver operating characteristic curves (AUROCs) were calculated for each population. RESULTS: The AUROC values for the Clinical Predictive Test alone were not significantly different from 0.50, the AUROC of a random classifier. Our Combined Clinical and Pharmacogenetic Predictive Test comprised of genetic polymorphisms in addition to FEV1 predicted poor BDR with an AUROC of 0.65 in the CAMP children (n = 422) and 0.60 (n = 475) and 0.63 (n = 235) in the two independent populations. Both the Combined Clinical and Pharmacogenetic Predictive Test and the Pharmacogenetic Predictive Test were significantly more accurate than the Clinical Predictive Test (AUROC between 0.44 and 0.55) in each of the populations. CONCLUSION: Our finding that genetic polymorphisms with a clinical trait are associated with BDR suggests that there is promise in using multiple genetic polymorphisms simultaneously to predict which asthmatics are likely to respond poorly to bronchodilators.},
edition = {2009/12/25},
canonical_id = {66923220-6d07-11df-afb8-0026b95d30b2},
added = {1363029758},
year = {2009},
keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Algorithms, Area Under Curve, Asthma/*diagnosis, Child, Clinical Trials as Topic, Female, Humans, Logistic Models, Male, Middle Aged, Pharmacogenetics/*methods, Polymorphism, Single Nucleotide/genetics, ROC Curve},
isstarred = {0},
id = {5296665511},
discipline = {Medicine},
journal = {Pharmacogenet Genomics},
title = {Development of a Pharmacogenetic Predictive Test in asthma: proof of concept},
deletionpending = {0},
version = {1363029947},
pmid = {20032818},
number = {2},
url_mendeley = {http://www.mendeley.com//research/development-pharmacogenetic-predictive-test-asthma-proof-concept//},
volume = {20},
source_type = {Journal Article},
isread = {0},
author = {A C {Wu} and B E {Himes} and J {Lasky-Su} and A {Litonjua} and L {Li} and C {Lange} and J {Lima} and C G {Irvin} and S T {Weiss}},
pages = {86-93},
doi = {10.1097/FPC.0b013e32833428d0},
language = {eng},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20032818},
type = {Journal Article},
notes = {Wu, Ann Chen
Himes, Blanca E
Lasky-Su, Jessica
Litonjua, Augusto
Li, Lingling
Lange, Christoph
Lima, John
Irvin, Charles G
Weiss, Scott T
HL071394/HL/NHLBI NIH HHS/United States
HL074755/HL/NHLBI NIH HHS/United States
P01 HL083069/HL/NHLBI NIH HHS/United States
R01 HL086601/HL/NHLBI NIH HHS/United States
T32 HL07427/HL/NHLBI NIH HHS/United States
U01 HL075419/HL/NHLBI NIH HHS/United States
U01 HL65899/HL/NHLBI NIH HHS/United States
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
United States
Pharmacogenetics and genomics
Pharmacogenet Genomics. 2010 Feb;20(2):86-93.},
modified = {1363029947},
journal = {Pharmacogenet Genomics},
subdiscipline = {None}
}
Downloads: 0
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T.</span>\n\t<!-- <span class=\"bibbase_paper_year\">2009</span>. -->\n</span>\n\n\n\n<i>Pharmacogenet Genomics</i>,\n\n20(2):86-93.\n\n 2009.\n\n\n\n\n<br class=\"bibbase_paper_content\"/>\n\n<span class=\"bibbase_paper_content\">\n \n \n <!-- <i -->\n <!-- onclick=\"javascript:log_download('wu-himes-laskysu-litonjua-li-lange-lima-irvin-weiss-developmentofapharmacogeneticpredictivetestinasthmaproofofconcept-2009', 'http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20032818')\">DEBUG -->\n <!-- </i> -->\n\n <a href=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20032818\"\n onclick=\"javascript:log_download('wu-himes-laskysu-litonjua-li-lange-lima-irvin-weiss-developmentofapharmacogeneticpredictivetestinasthmaproofofconcept-2009', 'http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20032818')\">\n <img src=\"http://bibbase.org/img/filetypes/blank.png\"\n\t alt=\"Development of a Pharmacogenetic Predictive Test in asthma: proof of concept [.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20032818]\" \n\t class=\"bibbase_icon\"\n\t style=\"width: 24px; height: 24px; border: 0px; vertical-align: text-top\" ><span class=\"bibbase_icon_text\">Paper</span></a> \n \n <!-- <i -->\n <!-- onclick=\"javascript:log_download('wu-himes-laskysu-litonjua-li-lange-lima-irvin-weiss-developmentofapharmacogeneticpredictivetestinasthmaproofofconcept-2009', 'http://www.mendeley.com//research/development-pharmacogenetic-predictive-test-asthma-proof-concept//')\">DEBUG -->\n <!-- </i> -->\n\n <a href=\"http://www.mendeley.com//research/development-pharmacogenetic-predictive-test-asthma-proof-concept//\"\n onclick=\"javascript:log_download('wu-himes-laskysu-litonjua-li-lange-lima-irvin-weiss-developmentofapharmacogeneticpredictivetestinasthmaproofofconcept-2009', 'http://www.mendeley.com//research/development-pharmacogenetic-predictive-test-asthma-proof-concept//')\">\n <img src=\"http://bibbase.org/img/filetypes/blank.png\"\n\t alt=\"Development of a Pharmacogenetic Predictive Test in asthma: proof of concept [.com//research/development-pharmacogenetic-predictive-test-asthma-proof-concept//]\" \n\t class=\"bibbase_icon\"\n\t style=\"width: 24px; height: 24px; border: 0px; vertical-align: text-top\" ><span class=\"bibbase_icon_text\">_mendeley</span></a> \n \n \n <a href=\"javascript:showBib('mendeley_5296665511')\">\n <img src=\"http://bibbase.org/img/filetypes/bib.png\" \n\t alt=\"Development of a Pharmacogenetic Predictive Test in asthma: proof of concept [bib]\" \n\t class=\"bibbase_icon\"\n\t style=\"width: 24px; height: 24px; border: 0px; vertical-align: text-top\"><span class=\"bibbase_icon_text\">Bibtex</span></a>\n \n \n\n \n \n \n \n \n\n \n <a class=\"bibbase_abstract_link\" href=\"javascript:showAbstract('mendeley_5296665511')\">Abstract</a>\n \n \n</span>\n\n<!-- -->\n<!-- <div id=\"abstract_mendeley_5296665511\"> -->\n<!-- OBJECTIVE: To assess the feasibility of developing a Combined Clinical and Pharmacogenetic Predictive Test, comprised of multiple single nucleotide polymorphisms (SNPs) that is associated with poor bronchodilator response (BDR). METHODS: We genotyped SNPs that tagged the whole genome of the parents and children in the Childhood Asthma Management Program (CAMP) and implemented an algorithm using a family-based association test that ranked SNPs by statistical power. The top eight SNPs that were associated with BDR comprised the Pharmacogenetic Predictive Test. The Clinical Predictive Test was comprised of baseline forced expiratory volume in 1 s (FEV1). We evaluated these predictive tests and a Combined Clinical and Pharmacogenetic Predictive Test in three distinct populations: the children of the CAMP trial and two additional clinical trial populations of asthma. Our outcome measure was poor BDR, defined as BDR of less than 20th percentile in each population. BDR was calculated as the percent difference between the prebronchodilator and postbronchodilator (two puffs of albuterol at 180 microg/puff) FEV1 value. To assess the predictive ability of the test, the corresponding area under the receiver operating characteristic curves (AUROCs) were calculated for each population. RESULTS: The AUROC values for the Clinical Predictive Test alone were not significantly different from 0.50, the AUROC of a random classifier. Our Combined Clinical and Pharmacogenetic Predictive Test comprised of genetic polymorphisms in addition to FEV1 predicted poor BDR with an AUROC of 0.65 in the CAMP children (n = 422) and 0.60 (n = 475) and 0.63 (n = 235) in the two independent populations. Both the Combined Clinical and Pharmacogenetic Predictive Test and the Pharmacogenetic Predictive Test were significantly more accurate than the Clinical Predictive Test (AUROC between 0.44 and 0.55) in each of the populations. CONCLUSION: Our finding that genetic polymorphisms with a clinical trait are associated with BDR suggests that there is promise in using multiple genetic polymorphisms simultaneously to predict which asthmatics are likely to respond poorly to bronchodilators. -->\n<!-- </div> -->\n<!-- -->\n\n</div>\n","downloads":0,"bibbaseid":"wu-himes-laskysu-litonjua-li-lange-lima-irvin-weiss-developmentofapharmacogeneticpredictivetestinasthmaproofofconcept-2009","urls":{"_mendeley":"http://www.mendeley.com//research/development-pharmacogenetic-predictive-test-asthma-proof-concept//","Paper":"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20032818"},"role":"author","year":"2009","volume":"20","version":"1363029947","url_mendeley":"http://www.mendeley.com//research/development-pharmacogenetic-predictive-test-asthma-proof-concept//","url":"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20032818","type":"Journal Article","title":"Development of a Pharmacogenetic Predictive Test in asthma: proof of concept","subdiscipline":"None","source_type":"Journal Article","pmid":"20032818","pages":"86-93","number":"2","notes":"Wu, Ann Chen Himes, Blanca E Lasky-Su, Jessica Litonjua, Augusto Li, Lingling Lange, Christoph Lima, John Irvin, Charles G Weiss, Scott T HL071394/HL/NHLBI NIH HHS/United States HL074755/HL/NHLBI NIH HHS/United States P01 HL083069/HL/NHLBI NIH HHS/United States R01 HL086601/HL/NHLBI NIH HHS/United States T32 HL07427/HL/NHLBI NIH HHS/United States U01 HL075419/HL/NHLBI NIH HHS/United States U01 HL65899/HL/NHLBI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Pharmacogenetics and genomics Pharmacogenet Genomics. 2010 Feb;20(2):86-93.","modified":"1363029947","language":"eng","keywords":"Adolescent, Adult, Aged, Aged, 80 and over, Algorithms, Area Under Curve, Asthma/*diagnosis, Child, Clinical Trials as Topic, Female, Humans, Logistic Models, Male, Middle Aged, Pharmacogenetics/*methods, Polymorphism, Single Nucleotide/genetics, ROC Curve","key":"mendeley_5296665511","journal":"Pharmacogenet Genomics","isstarred":"0","isread":"0","isbn":"1744-6880 (Electronic) 1744-6872 (Linking)","isauthor":"1","id":"mendeley_5296665511","edition":"2009/12/25","doi":"10.1097/FPC.0b013e32833428d0","discipline":"Medicine","deletionpending":"0","canonical_id":"66923220-6d07-11df-afb8-0026b95d30b2","bibtype":"article","bibtex":"@article{ mendeley_5296665511,\n isauthor = {1},\n isbn = {1744-6880 (Electronic)\r1744-6872 (Linking)},\n abstract = {OBJECTIVE: To assess the feasibility of developing a Combined Clinical and Pharmacogenetic Predictive Test, comprised of multiple single nucleotide polymorphisms (SNPs) that is associated with poor bronchodilator response (BDR). METHODS: We genotyped SNPs that tagged the whole genome of the parents and children in the Childhood Asthma Management Program (CAMP) and implemented an algorithm using a family-based association test that ranked SNPs by statistical power. The top eight SNPs that were associated with BDR comprised the Pharmacogenetic Predictive Test. The Clinical Predictive Test was comprised of baseline forced expiratory volume in 1 s (FEV1). We evaluated these predictive tests and a Combined Clinical and Pharmacogenetic Predictive Test in three distinct populations: the children of the CAMP trial and two additional clinical trial populations of asthma. Our outcome measure was poor BDR, defined as BDR of less than 20th percentile in each population. BDR was calculated as the percent difference between the prebronchodilator and postbronchodilator (two puffs of albuterol at 180 microg/puff) FEV1 value. To assess the predictive ability of the test, the corresponding area under the receiver operating characteristic curves (AUROCs) were calculated for each population. RESULTS: The AUROC values for the Clinical Predictive Test alone were not significantly different from 0.50, the AUROC of a random classifier. Our Combined Clinical and Pharmacogenetic Predictive Test comprised of genetic polymorphisms in addition to FEV1 predicted poor BDR with an AUROC of 0.65 in the CAMP children (n = 422) and 0.60 (n = 475) and 0.63 (n = 235) in the two independent populations. Both the Combined Clinical and Pharmacogenetic Predictive Test and the Pharmacogenetic Predictive Test were significantly more accurate than the Clinical Predictive Test (AUROC between 0.44 and 0.55) in each of the populations. CONCLUSION: Our finding that genetic polymorphisms with a clinical trait are associated with BDR suggests that there is promise in using multiple genetic polymorphisms simultaneously to predict which asthmatics are likely to respond poorly to bronchodilators.},\n edition = {2009/12/25},\n canonical_id = {66923220-6d07-11df-afb8-0026b95d30b2},\n added = {1363029758},\n year = {2009},\n keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Algorithms, Area Under Curve, Asthma/*diagnosis, Child, Clinical Trials as Topic, Female, Humans, Logistic Models, Male, Middle Aged, Pharmacogenetics/*methods, Polymorphism, Single Nucleotide/genetics, ROC Curve},\n isstarred = {0},\n id = {5296665511},\n discipline = {Medicine},\n journal = {Pharmacogenet Genomics},\n title = {Development of a Pharmacogenetic Predictive Test in asthma: proof of concept},\n deletionpending = {0},\n version = {1363029947},\n pmid = {20032818},\n number = {2},\n url_mendeley = {http://www.mendeley.com//research/development-pharmacogenetic-predictive-test-asthma-proof-concept//},\n volume = {20},\n source_type = {Journal Article},\n isread = {0},\n author = {A C {Wu} and B E {Himes} and J {Lasky-Su} and A {Litonjua} and L {Li} and C {Lange} and J {Lima} and C G {Irvin} and S T {Weiss}},\n pages = {86-93},\n doi = {10.1097/FPC.0b013e32833428d0},\n language = {eng},\n url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20032818},\n type = {Journal Article},\n notes = {Wu, Ann Chen\nHimes, Blanca E\nLasky-Su, Jessica\nLitonjua, Augusto\nLi, Lingling\nLange, Christoph\nLima, John\nIrvin, Charles G\nWeiss, Scott T\nHL071394/HL/NHLBI NIH HHS/United States\nHL074755/HL/NHLBI NIH HHS/United States\nP01 HL083069/HL/NHLBI NIH HHS/United States\nR01 HL086601/HL/NHLBI NIH HHS/United States\nT32 HL07427/HL/NHLBI NIH HHS/United States\nU01 HL075419/HL/NHLBI NIH HHS/United States\nU01 HL65899/HL/NHLBI NIH HHS/United States\nResearch Support, N.I.H., Extramural\nResearch Support, Non-U.S. Gov't\nUnited States\nPharmacogenetics and genomics\nPharmacogenet Genomics. 2010 Feb;20(2):86-93.},\n modified = {1363029947},\n journal = {Pharmacogenet Genomics},\n subdiscipline = {None}\n}","author_short":["Wu, A.<nbsp>C.","Himes, B.<nbsp>E.","Lasky-Su, J.","Litonjua, A.","Li, L.","Lange, C.","Lima, J.","Irvin, C.<nbsp>G.","Weiss, S.<nbsp>T."],"author":["Wu, A C","Himes, B E","Lasky-Su, J","Litonjua, A","Li, L","Lange, C","Lima, J","Irvin, C G","Weiss, S T"],"added":"1363029758","abstract":"OBJECTIVE: To assess the feasibility of developing a Combined Clinical and Pharmacogenetic Predictive Test, comprised of multiple single nucleotide polymorphisms (SNPs) that is associated with poor bronchodilator response (BDR). METHODS: We genotyped SNPs that tagged the whole genome of the parents and children in the Childhood Asthma Management Program (CAMP) and implemented an algorithm using a family-based association test that ranked SNPs by statistical power. The top eight SNPs that were associated with BDR comprised the Pharmacogenetic Predictive Test. The Clinical Predictive Test was comprised of baseline forced expiratory volume in 1 s (FEV1). We evaluated these predictive tests and a Combined Clinical and Pharmacogenetic Predictive Test in three distinct populations: the children of the CAMP trial and two additional clinical trial populations of asthma. Our outcome measure was poor BDR, defined as BDR of less than 20th percentile in each population. BDR was calculated as the percent difference between the prebronchodilator and postbronchodilator (two puffs of albuterol at 180 microg/puff) FEV1 value. To assess the predictive ability of the test, the corresponding area under the receiver operating characteristic curves (AUROCs) were calculated for each population. RESULTS: The AUROC values for the Clinical Predictive Test alone were not significantly different from 0.50, the AUROC of a random classifier. Our Combined Clinical and Pharmacogenetic Predictive Test comprised of genetic polymorphisms in addition to FEV1 predicted poor BDR with an AUROC of 0.65 in the CAMP children (n = 422) and 0.60 (n = 475) and 0.63 (n = 235) in the two independent populations. Both the Combined Clinical and Pharmacogenetic Predictive Test and the Pharmacogenetic Predictive Test were significantly more accurate than the Clinical Predictive Test (AUROC between 0.44 and 0.55) in each of the populations. CONCLUSION: Our finding that genetic polymorphisms with a clinical trait are associated with BDR suggests that there is promise in using multiple genetic polymorphisms simultaneously to predict which asthmatics are likely to respond poorly to bronchodilators."},"bibtype":"article","biburl":"http://www.bibbase.org/mendeley/4764926815","downloads":0,"title":"Development of a Pharmacogenetic Predictive Test in asthma: proof of concept","year":2009,"dataSources":["ehtbJF5rqvNg4MNjT"]}