Fig. 1.

Flow of the analysis in this study. In total, 2630 patients with IBD were enrolled. All the patients were genotyped for NUDT15 codon 139. The number of patients exposed to thiopurines was 1291; additional genetic analyses were performed on 995 of these 1291 patients. This study consisted of five analyses: (analysis 1) association study of NUDT15 p.Arg139Cys with adverse events of other IBD drugs; (analysis 2) association analysis of NUDT15 codon 139 with thiopurine-induced adverse events; (analysis 3) diplotype-based association study of NUDT15 with thiopurines; (analysis 4) GWAS of thiopurine-induced adverse events; (analysis 5) ROC analysis to investigate the best model to predict thiopurine-induced severe AEs in Japanese patients with IBD