Long-term IFN-β therapy has been associated with the increased incidence of adverse CNS effects including depression and ‘flu-like symptoms’ such as fever, muscle aches and headaches, which have been noted as a major factor for MS patients to discontinue IFN-β therapy in addition to poorly perceived efficacy (Neilley et al., 1996; O’Rourke and Hutchinson, 2005; Fox et al., 2013). Here, IFNB1 is linked to major depressive disorder.