<em>HLA-DQA1-HLA-DRB1</em> variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants

Functional dependencies (FDs) specify the intended data semantics while violations of FDs indicate deviation from these semantics. In this paper, we study a data cleaning problem in which the FDs may not be completely correct, e.g., due to data evolution or incomplete knowledge of the data semantics. We argue that the notion of relative trust is a crucial aspect of this problem: if the FDs are outdated, we should modify them to fit the data, but if we suspect that there are problems with the data, we should modify the data to fit the FDs. In practice, it is usually unclear how much to trust the data versus the FDs. To address this problem, we propose an algorithm for generating non-redundant solutions (i.e., simultaneous modifications of the data and the FDs) corresponding to various levels of relative trust. This can help users determine the best way to modify their data and/or FDs to achieve consistency

HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants.

Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 x 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the H LA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk