As a third feature, we used electronic medical records to comprehensively investigate pleiotropy of RA-associated TYK2 variants that could predict potential adverse events, including risk of serious infections, decreased WBC or neutrophil counts, or increased LDL levels, which are major adverse drug events in RA drug development that have been observed in clinical trials of tofacitinib [54,55,64] (Fig 5 and S3 Fig). Here, TYK2 is linked to rheumatoid arthritis.