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Phenome-Wide Association Studies on a Quantitative Trait: Application to TPMT Enzyme Activity and Thiopurine Therapy in Pharmacogenomics

Phenome-Wide Association Studies (PheWAS) investigate whether genetic polymorphisms associated with a phenotype are also associated with other diagnoses. In this study, we have developed new methods to perform a PheWAS based on ICD-10 codes and biological test results, and to use a quantitative trai...

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Autores principales: Neuraz, Antoine, Chouchana, Laurent, Malamut, Georgia, Le Beller, Christine, Roche, Denis, Beaune, Philippe, Degoulet, Patrice, Burgun, Anita, Loriot, Marie-Anne, Avillach, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873228/
https://www.ncbi.nlm.nih.gov/pubmed/24385893
http://dx.doi.org/10.1371/journal.pcbi.1003405
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author Neuraz, Antoine
Chouchana, Laurent
Malamut, Georgia
Le Beller, Christine
Roche, Denis
Beaune, Philippe
Degoulet, Patrice
Burgun, Anita
Loriot, Marie-Anne
Avillach, Paul
author_facet Neuraz, Antoine
Chouchana, Laurent
Malamut, Georgia
Le Beller, Christine
Roche, Denis
Beaune, Philippe
Degoulet, Patrice
Burgun, Anita
Loriot, Marie-Anne
Avillach, Paul
author_sort Neuraz, Antoine
collection PubMed
description Phenome-Wide Association Studies (PheWAS) investigate whether genetic polymorphisms associated with a phenotype are also associated with other diagnoses. In this study, we have developed new methods to perform a PheWAS based on ICD-10 codes and biological test results, and to use a quantitative trait as the selection criterion. We tested our approach on thiopurine S-methyltransferase (TPMT) activity in patients treated by thiopurine drugs. We developed 2 aggregation methods for the ICD-10 codes: an ICD-10 hierarchy and a mapping to existing ICD-9-CM based PheWAS codes. Eleven biological test results were also analyzed using discretization algorithms. We applied these methods in patients having a TPMT activity assessment from the clinical data warehouse of a French academic hospital between January 2000 and July 2013. Data after initiation of thiopurine treatment were analyzed and patient groups were compared according to their TPMT activity level. A total of 442 patient records were analyzed representing 10,252 ICD-10 codes and 72,711 biological test results. The results from the ICD-9-CM based PheWAS codes and ICD-10 hierarchy codes were concordant. Cross-validation with the biological test results allowed us to validate the ICD phenotypes. Iron-deficiency anemia and diabetes mellitus were associated with a very high TPMT activity (p = 0.0004 and p = 0.0015, respectively). We describe here an original method to perform PheWAS on a quantitative trait using both ICD-10 diagnosis codes and biological test results to identify associated phenotypes. In the field of pharmacogenomics, PheWAS allow for the identification of new subgroups of patients who require personalized clinical and therapeutic management.
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spelling pubmed-38732282014-01-02 Phenome-Wide Association Studies on a Quantitative Trait: Application to TPMT Enzyme Activity and Thiopurine Therapy in Pharmacogenomics Neuraz, Antoine Chouchana, Laurent Malamut, Georgia Le Beller, Christine Roche, Denis Beaune, Philippe Degoulet, Patrice Burgun, Anita Loriot, Marie-Anne Avillach, Paul PLoS Comput Biol Research Article Phenome-Wide Association Studies (PheWAS) investigate whether genetic polymorphisms associated with a phenotype are also associated with other diagnoses. In this study, we have developed new methods to perform a PheWAS based on ICD-10 codes and biological test results, and to use a quantitative trait as the selection criterion. We tested our approach on thiopurine S-methyltransferase (TPMT) activity in patients treated by thiopurine drugs. We developed 2 aggregation methods for the ICD-10 codes: an ICD-10 hierarchy and a mapping to existing ICD-9-CM based PheWAS codes. Eleven biological test results were also analyzed using discretization algorithms. We applied these methods in patients having a TPMT activity assessment from the clinical data warehouse of a French academic hospital between January 2000 and July 2013. Data after initiation of thiopurine treatment were analyzed and patient groups were compared according to their TPMT activity level. A total of 442 patient records were analyzed representing 10,252 ICD-10 codes and 72,711 biological test results. The results from the ICD-9-CM based PheWAS codes and ICD-10 hierarchy codes were concordant. Cross-validation with the biological test results allowed us to validate the ICD phenotypes. Iron-deficiency anemia and diabetes mellitus were associated with a very high TPMT activity (p = 0.0004 and p = 0.0015, respectively). We describe here an original method to perform PheWAS on a quantitative trait using both ICD-10 diagnosis codes and biological test results to identify associated phenotypes. In the field of pharmacogenomics, PheWAS allow for the identification of new subgroups of patients who require personalized clinical and therapeutic management. Public Library of Science 2013-12-26 /pmc/articles/PMC3873228/ /pubmed/24385893 http://dx.doi.org/10.1371/journal.pcbi.1003405 Text en © 2013 Neuraz et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Neuraz, Antoine
Chouchana, Laurent
Malamut, Georgia
Le Beller, Christine
Roche, Denis
Beaune, Philippe
Degoulet, Patrice
Burgun, Anita
Loriot, Marie-Anne
Avillach, Paul
Phenome-Wide Association Studies on a Quantitative Trait: Application to TPMT Enzyme Activity and Thiopurine Therapy in Pharmacogenomics
title Phenome-Wide Association Studies on a Quantitative Trait: Application to TPMT Enzyme Activity and Thiopurine Therapy in Pharmacogenomics
title_full Phenome-Wide Association Studies on a Quantitative Trait: Application to TPMT Enzyme Activity and Thiopurine Therapy in Pharmacogenomics
title_fullStr Phenome-Wide Association Studies on a Quantitative Trait: Application to TPMT Enzyme Activity and Thiopurine Therapy in Pharmacogenomics
title_full_unstemmed Phenome-Wide Association Studies on a Quantitative Trait: Application to TPMT Enzyme Activity and Thiopurine Therapy in Pharmacogenomics
title_short Phenome-Wide Association Studies on a Quantitative Trait: Application to TPMT Enzyme Activity and Thiopurine Therapy in Pharmacogenomics
title_sort phenome-wide association studies on a quantitative trait: application to tpmt enzyme activity and thiopurine therapy in pharmacogenomics
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873228/
https://www.ncbi.nlm.nih.gov/pubmed/24385893
http://dx.doi.org/10.1371/journal.pcbi.1003405
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