The opposite effects of interferon signaling on systemic lupus erythematosus and inflammatory bowel disease are demonstrated by the effects of rare variants in IFIH1 which encodes a cytosolic sensor of dsRNA that initiates signaling via Type I interferons (interferon-α and interferon-β) and Type III interferons (interferon-λ1 to interferon-λ4). Here, IFIH1 is linked to inflammatory bowel disease.