Multiple variants in IFN genes linked to mortality and discrete phenotypes of SSc, such as dcSSc, lcSSc, anti-DNA topoisomerase I antibody (ATA), anticentromere antibodies (ACA), and pulmonary arterial hypertension (PAH), point to the importance of the IFN pathway, both in the development and progression of SSc. The gene discussed is TOP1; the disease is systemic sclerosis.