TYMS and rheumatoid arthritis: To date, two GWAS have been performed involving MTX activity: Senapati et al. [25] suggested multiple novel risk loci involved in thymidylate synthase (TYMS) regulation, and Taylor et al. [26] conducted the largest GWAS on MTX response, including 1424 early RA patients and finding a suggestive association in neuregulin 3 (NRG3).