{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T21:53:22Z","timestamp":1759960402380},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2013,12,26]],"date-time":"2013-12-26T00:00:00Z","timestamp":1388016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1003405","type":"journal-article","created":{"date-parts":[[2013,12,26]],"date-time":"2013-12-26T21:18:09Z","timestamp":1388092689000},"page":"e1003405","update-policy":"http:\/\/dx.doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":47,"title":["Phenome-Wide Association Studies on a Quantitative Trait: Application to TPMT Enzyme Activity and Thiopurine Therapy in Pharmacogenomics"],"prefix":"10.1371","volume":"9","author":[{"given":"Antoine","family":"Neuraz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Chouchana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia","family":"Malamut","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Le Beller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Roche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Beaune","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrice","family":"Degoulet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Burgun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Anne","family":"Loriot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Avillach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2013,12,26]]},"reference":[{"key":"ref1","unstructured":"(2011) Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. Washington, D.C.): National Academies Press (US)."},{"key":"ref2","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1056\/NEJMra0907175","article-title":"Genomic medicine\u2013an updated primer","volume":"362","author":"WG Feero","year":"2010","journal-title":"N Engl J Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1126\/science.1109557","article-title":"Complement Factor H Polymorphism in Age-Related Macular Degeneration","volume":"308","author":"RJ Klein","year":"2005","journal-title":"Science"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"9362","DOI":"10.1073\/pnas.0903103106","article-title":"Potential etiologic and functional implications of genome-wide association loci for human diseases and traits","volume":"106","author":"LA Hindorff","year":"2009","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/nature06258","article-title":"A second generation human haplotype map of over 3.1 million SNPs","volume":"449","author":"KA Frazer","year":"2007","journal-title":"Nature"},{"key":"ref6","unstructured":"Hindorff LA, MacArthur J (European Bioinformatics Institute), Morales J (European Bioinformatics Institute), Junkins HA, Hall PN, <etal>et al<\/etal>.. (n.d.) A Catalog of Published Genome-Wide Association Studies. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.genome.gov\/gwastudies\/\" xlink:type=\"simple\">http:\/\/www.genome.gov\/gwastudies\/<\/ext-link>. Accessed 9 April 2013."},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1093\/bioinformatics\/btq126","article-title":"PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations","volume":"26","author":"JC Denny","year":"2010","journal-title":"Bioinformatics"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.ajhg.2011.09.008","article-title":"Variants near FOXE1 are associated with hypothyroidism and other thyroid conditions: using electronic medical records for genome- and phenome-wide studies","volume":"89","author":"JC Denny","year":"2011","journal-title":"American journal of human genetics"},{"key":"ref9","unstructured":"WHO (2010) WHO | International Classification of Diseases (ICD). Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.who.int\/classifications\/icd\/en\/\" xlink:type=\"simple\">http:\/\/www.who.int\/classifications\/icd\/en\/<\/ext-link>. Accessed 5 January 2013."},{"key":"ref10","first-page":"362","article-title":"Development of a large-scale de-identified DNA biobank to enable personalized medicine","volume":"84","author":"DM Roden","year":"2008","journal-title":"ClinPharmacolTher"},{"key":"ref11","article-title":"Autoantibodies, autoimmune risk alleles and clinical associations in rheumatoid arthritis cases and non-RA controls in the electronic medical records","author":"KP Liao","year":"2012","journal-title":"Arthritis Rheum"},{"key":"ref12","article-title":"A PheWAS approach in studying HLA-DRB1*1501","author":"SJ Hebbring","year":"2013","journal-title":"Genes Immun"},{"key":"ref13","first-page":"79re1","article-title":"Electronic medical records for genetic research: results of the eMERGE consortium","volume":"3","author":"AN Kho","year":"2011","journal-title":"SciTransl Med"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1002\/gepi.20589","article-title":"The use of phenome-wide association studies (PheWAS) for exploration of novel genotype-phenotype relationships and pleiotropy discovery","volume":"35","author":"SA Pendergrass","year":"2011","journal-title":"Genetic epidemiology"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"e1003087","DOI":"10.1371\/journal.pgen.1003087","article-title":"Phenome-Wide Association Study (PheWAS) for Detection of Pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network","volume":"9","author":"SA Pendergrass","year":"2013","journal-title":"PLoS Genet"},{"key":"ref16","unstructured":"Ritchie MD, Denny JC, Zuvich RL, Crawford DC, Schildcrout JS, <etal>et al<\/etal>.. (2013) Genome- and Phenome-Wide Analysis of Cardiac Conduction Identifies Markers of Arrhythmia Risk. Circulation. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/circ.ahajournals.org\/content\/early\/2013\/03\/05\/CIRCULATIONAHA.112.000604\" xlink:type=\"simple\">http:\/\/circ.ahajournals.org\/content\/early\/2013\/03\/05\/CIRCULATIONAHA.112.000604<\/ext-link>. Accessed 20 March 2013."},{"key":"ref17","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.1136\/amiajnl-2012-000969","article-title":"The coming age of data-driven medicine: translational bioinformatics&apos; next frontier","volume":"19","author":"NH Shah","year":"2012","journal-title":"J Am Med Inform Assoc"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1109\/MIS.2009.36","article-title":"The Unreasonable Effectiveness of Data","volume":"24","author":"A Halevy","year":"2009","journal-title":"IEEE Intelligent Systems"},{"key":"ref19","first-page":"391","article-title":"STRIDE\u2013An integrated standards-based translational research informatics platform","volume":"2009","author":"HJ Lowe","year":"2009","journal-title":"AMIA AnnuSympProc"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1136\/jamia.2009.000893","article-title":"Serving the enterprise and beyond with informatics for integrating biology and the bedside (i2b2)","volume":"17","author":"SN Murphy","year":"2010","journal-title":"Journal of the American Medical Informatics Association: JAMIA"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1479-5876-8-68","article-title":"Effective knowledge management in translational medicine","volume":"8","author":"S Szalma","year":"2010","journal-title":"J Transl Med"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1056\/NEJMe1213371","article-title":"A glimpse of the next 100 years in medicine","volume":"367","author":"IS Kohane","year":"2012","journal-title":"N Engl J Med"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/clpt.2012.49","article-title":"Translational Bioinformatics: Linking the Molecular World to the Clinical World","volume":"91","author":"RB Altman","year":"2012","journal-title":"Clinical Pharmacology & Therapeutics"},{"key":"ref24","first-page":"e1002823","article-title":"Chapter 13: Mining Electronic Health Records in the Genomics Era","volume":"8","author":"JC Denny","year":"2012","journal-title":"PLoSComputBiol"},{"key":"ref25","first-page":"e1002141","article-title":"Using Electronic Patient Records to Discover Disease Correlations and Stratify Patient Cohorts","volume":"7","author":"FS Roque","year":"2011","journal-title":"PLoSComputBiol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/1471-2105-13-S14-S1","article-title":"Clinical Bioinformatics: challenges and opportunities","volume":"13 Suppl 14","author":"R Bellazzi","year":"2012","journal-title":"BMC Bioinformatics"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.crohns.2012.04.003","article-title":"TPMT status determination: the simplest is the most effective?","volume":"6","author":"L Chouchana","year":"2012","journal-title":"J Crohns Colitis"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1097\/01.fpc.0000114745.08559.db","article-title":"Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants","volume":"14","author":"E Schaeffeler","year":"2004","journal-title":"Pharmacogenetics"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1365-2036.2011.04905.x","article-title":"Review article: the benefits of pharmacogenetics for improving thiopurine therapy in inflammatory bowel disease","volume":"35","author":"L Chouchana","year":"2012","journal-title":"Alimentary pharmacology & therapeutics"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/clpt.2010.320","article-title":"Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing","volume":"89","author":"MV Relling","year":"2011","journal-title":"Clinical pharmacology and therapeutics"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.dld.2005.08.003","article-title":"TPMT genotype and the use of thiopurines in paediatric inflammatory bowel disease","volume":"37","author":"G Stocco","year":"2005","journal-title":"Dig Liver Dis"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1136\/gut.50.4.485","article-title":"The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review","volume":"50","author":"AG Fraser","year":"2002","journal-title":"Gut"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1053\/gast.2002.32420","article-title":"6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease","volume":"122","author":"MC Dubinsky","year":"2002","journal-title":"Gastroenterology"},{"key":"ref34","first-page":"18","article-title":"Thiopurine pharmacogenetics in leukemia: correlation of erythrocyte thiopurine methyltransferase activity and 6-thioguanine nucleotide concentrations","volume":"41","author":"L Lennard","year":"1987","journal-title":"ClinPharmacolTher"},{"key":"ref35","first-page":"651","article-title":"Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity","volume":"32","author":"RM Weinshilboum","year":"1980","journal-title":"Am J Hum Genet"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/FPC.0b013e32835f1cc0","article-title":"Nomenclature for alleles of the thiopurine methyltransferase gene","volume":"23","author":"ML Appell","year":"2013","journal-title":"Pharmacogenet Genomics"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1046\/j.1365-2036.2002.01353.x","article-title":"Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease","volume":"16","author":"A Ansari","year":"2002","journal-title":"Aliment PharmacolTher"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1373\/clinchem.2012.195750","article-title":"Poor response to thiopurine in inflammatory bowel disease: how to overcome therapeutic resistance?","volume":"59","author":"L Chouchana","year":"2013","journal-title":"Clin Chem"},{"key":"ref39","first-page":"193","article-title":"Methodology of integration of a clinical data warehouse with a clinical information system: the HEGP case","volume":"160","author":"E Zapletal","year":"2010","journal-title":"Studies in health technology and informatics"},{"key":"ref40","unstructured":"Mapping between ICD-10 and ICD-9 (2000). Ministry of Health of New Zealand. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.health.govt.nz\/nz-health-statistics\/data-references\/mapping-tools\/mapping-between-icd-10-and-icd-9\" xlink:type=\"simple\">http:\/\/www.health.govt.nz\/nz-health-statistics\/data-references\/mapping-tools\/mapping-between-icd-10-and-icd-9<\/ext-link>. Accessed 8 February 2013."},{"key":"ref41","first-page":"815","article-title":"Beyond synonymy: exploiting the UMLS semantics in mapping vocabularies","author":"O Bodenreider","year":"1998","journal-title":"Proc AMIA Symp"},{"key":"ref42","unstructured":"Denny J (2013) ICD9 to PheWAS: Code translation map. Vanderbilt University. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/knowledgemap2.mc.vanderbilt.edu\/research\/sites\/default\/files\/code_translation.txt\" xlink:type=\"simple\">http:\/\/knowledgemap2.mc.vanderbilt.edu\/research\/sites\/default\/files\/code_translation.txt<\/ext-link>. Accessed 8 January 2013."},{"key":"ref43","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S1570-0232(02)00130-7","article-title":"Thiopurine methyltransferase activity: new conditions for reversed-phase high-performance liquid chromatographic assay without extraction and genotypic-phenotypic correlation","volume":"773","author":"D Anglicheau","year":"2002","journal-title":"J Chromatogr B AnalytTechnol Biomed Life Sci"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","author":"Y Benjamini","year":"1995","journal-title":"Journal of the Royal Statistical Society Series B (Methodological)"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/2041-1480-3-10","article-title":"Applying semantic web technologies for phenome-wide scan using an electronic health record linked Biobank","volume":"3","author":"J Pathak","year":"2012","journal-title":"J Biomed Semantics"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3324\/haematol.2009.009985","article-title":"Prevalence and pathogenesis of anemia in inflammatory bowel disease.Influence of anti-tumor necrosis factor-alpha treatment","volume":"95","author":"G Bergamaschi","year":"2010","journal-title":"Haematologica"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/S0022-3476(05)83063-X","article-title":"Altered mercaptopurine metabolism, toxic effects, and dosage requirement in a thiopurine methyltransferase-deficient child with acute lymphocytic leukemia","volume":"119","author":"WE Evans","year":"1991","journal-title":"J Pediatr"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1080\/01621459.1955.10501294","article-title":"A Multiple Comparison Procedure for Comparing Several Treatments with a Control","volume":"50","author":"CW Dunnett","year":"1955","journal-title":"Journal of the American Statistical Association"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1093\/bioinformatics\/btf877","article-title":"Identifying differentially expressed genes using false discovery rate controlling procedures","volume":"19","author":"A Reiner","year":"2003","journal-title":"Bioinformatics"},{"key":"ref50","article-title":"Intrauterine exposure and pharmacology of conventional thiopurine therapy in pregnant patients with inflammatory bowel disease","author":"B Jharap","year":"2013","journal-title":"Gut"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"486","DOI":"10.7326\/0003-4819-146-7-200704030-00004","article-title":"Prevalence of Neutropenia in the U.S. Population: Age, Sex, Smoking Status, and Ethnic Differences","volume":"146","author":"MM Hsieh","year":"2007","journal-title":"Ann Intern Med"},{"key":"ref52","unstructured":"WHO (2011) WHO|Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.who.int\/vmnis\/indicators\/haemoglobin\/en\/index.html\" xlink:type=\"simple\">http:\/\/www.who.int\/vmnis\/indicators\/haemoglobin\/en\/index.html<\/ext-link>. Accessed 29 January 2013."},{"key":"ref53","unstructured":"WHO (2006) WHO|Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.who.int\/diabetes\/publications\/diagnosis_diabetes2006\/en\/index.html\" xlink:type=\"simple\">http:\/\/www.who.int\/diabetes\/publications\/diagnosis_diabetes2006\/en\/index.html<\/ext-link>. Accessed 28 January 2013."}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003405","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T10:27:34Z","timestamp":1565000854000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003405"}},"subtitle":[],"editor":[{"given":"Donna K.","family":"Slonim","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2013,12,26]]},"references-count":53,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2013,12,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1003405","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,26]]}}}