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Aim: ‘Pharmacoepigenomics’ methods informed by omics datasets and pre-existing knowledge have yielded discoveries in neuropsychiatric pharmacogenomics. Now we evaluate the generality of these methods by discovering an extended warfarin pharmacogenomics pathway. Materials &amp; methods: We developed the pharmacoepigenomics informatics pipeline, a scalable multi-omics variant screening pipeline for pharmacogenomics, and conducted an experiment in the genomics of warfarin. Results: We discovered known and novel pharmacogenomics variants and genes, both coding and regulatory, for warfarin response, including adverse events. Such genes and variants cluster in a warfarin response pathway consolidating known and novel warfarin response variants and genes. Conclusion: These results can inform a new warfarin test. The pharmacoepigenomics informatics pipeline may be able to discover new pharmacogenomics markers in other drug-disease systems.

The pharmacoepigenomics informatics pipeline defines a pathway of novel and known warfarin pharmacogenomics variants