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Exome data for 100 patients were assessed against biochemically measured TPMT enzyme activity, clinical response and adverse effects. The <jats:italic>TPMT<\/jats:italic> gene and a panel of 15 other genes implicated in thiopurine toxicity were analysed using a gene based statistical test (SKAT-O test). Nine patients out of 100 (Crohn\u2019s disease- 67, ulcerative colitis- 23 and IBDU-10) had known <jats:italic>TPMT<\/jats:italic> mutations associated with deficient enzyme activity. A novel and a highly pathogenic <jats:italic>TPMT<\/jats:italic> variant not detectable through standard genotyping, was identified through NGS in an individual intolerant to thiopurines. Of the 14 patients intolerant to thiopurines, NGS identified deleterious <jats:italic>TPMT<\/jats:italic> variants in 5 individuals whereas the biochemical test identified 8 individuals as intolerant (sensitivity 35.7% and 57.14%; specificity 93.75% and 50% respectively). SKAT-O test identified a significant association between <jats:italic>MOCOS<\/jats:italic> gene and TPMT activity (p\u2009=\u20090.0015), not previously reported. Although NGS has the ability to detect rare or novel variants not otherwise identified through standard genotyping, it demonstrates no clear advantage over the biochemical test in predicting toxicity in our modest cohort.<\/jats:p>","DOI":"10.1038\/srep34658","type":"journal-article","created":{"date-parts":[[2016,10,5]],"date-time":"2016-10-05T09:20:01Z","timestamp":1475659201000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Genes implicated in thiopurine-induced toxicity: Comparing TPMT enzyme activity with clinical phenotype and exome data in a paediatric IBD cohort"],"prefix":"10.1038","volume":"6","author":[{"given":"Tracy","family":"Coelho","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaia","family":"Andreoletti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James J.","family":"Ashton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akshay","family":"Batra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadeem Ahmad","family":"Afzal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony P.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert M.","family":"Beattie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Ennis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,10,5]]},"reference":[{"key":"BFsrep34658_CR1","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1056\/NEJM198005013021801","volume":"302","author":"DH Present","year":"1980","unstructured":"Present, D. 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